{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:48:03Z","timestamp":1792792083125,"version":"4.5.0"},"reference-count":96,"publisher":"American Association for the Advancement of Science (AAAS)","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":288,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002745","name":"Bavarian Research Foundation","doi-asserted-by":"publisher","award":["324392634 \\u2013 TRR 221\/INF"],"award-info":[{"award-number":["324392634 \\u2013 TRR 221\/INF"]}],"id":[{"id":"10.13039\/501100002745","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002745","name":"Bavarian Research Foundation","doi-asserted-by":"publisher","award":["AZ-1365\\u201318"],"award-info":[{"award-number":["AZ-1365\\u201318"]}],"id":[{"id":"10.13039\/501100002745","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002745","name":"Bavarian Research Foundation","doi-asserted-by":"publisher","award":["JNP DOK-184\\u201320"],"award-info":[{"award-number":["JNP DOK-184\\u201320"]}],"id":[{"id":"10.13039\/501100002745","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008769","name":"Julius-Maximilians-Universit\u00e4t W\u00fcrzburg","doi-asserted-by":"publisher","award":["19_2021_11"],"award-info":[{"award-number":["19_2021_11"]}],"id":[{"id":"10.13039\/501100008769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007440","name":"Hans B\u00f6ckler Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["270563345 \/GRK2157 3DInfect"],"award-info":[{"award-number":["270563345 \/GRK2157 3DInfect"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["492620490"],"award-info":[{"award-number":["492620490"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["csbj.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Comput Struct Biotechnol J"],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec sec-type=\"background\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pancreatic ductal adenocarcinoma is characterized by high levels of chemoresistance and aggressive progression of the disease, which is a major challenge for effective treatment. Conventional 2D cultures capture therapy resistance only to a limited extent, whereas 3D cultures may better reflect relevant conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec sec-type=\"materials-methods\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We established 3D PANC-1 tissue models based on a decellularized porcine jejunum with niche-specific drug response to gemcitabine (GEM) treatment. TGFB1 induced invasion and further drug resistance. Thus, we performed scRNA-seq after treatment with GEM, TGFB1 stimulation, or both. Data were analyzed using standard approaches and a novel mutual-information-based machine learning framework (gSELECT). Candidate genes were further evaluated through enrichment and survival analyses.<\/jats:p>\n                    <jats:p>Additionally, we present a novel mathematical approach as proof of concept for analyzing differences in gene expression between groups seemingly similar with respect to a projection such as t-SNE or UMAP (e.g., GEM-treated and untreated cells). For this, we stratified control cells by similarity to GEM-treated survivors, yielding predicted-resistant and predicted-sensitive subgroups for downstream analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec sec-type=\"results\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Pre-analysis using machine learning and comparative analyses of single-cell RNA sequencing data showed only minor differences in gene expression in response to GEM treatment, whereas TGFB1 induced an invasive phenotype characterized by EMT-related transcriptional changes, including downregulation of cytokeratins.<\/jats:p>\n                    <jats:p>Laboratory experiments showed that \u223c75\u202f% of PANC-1 cells survived GEM in 3D, indicating intrinsic resistance. Our mathematical approach using machine learning predicted a GEM-sensitive subpopulation consistent with these findings. Comparative analyses revealed mutual information (MI) genes distinguishing sensitive from resistant cells, several of which were supported by literature and survival data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec sec-type=\"conclusion\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Computational analysis of scRNA-seq data from 3D-cultured PANC-1 cells provides a useful framework for studying treatment effects. The potential relevance of the identified MI genes is supported by further\n                      <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                      analyses. Based on\n                      <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                      analyses, we demonstrate the analytical value of our mathematical approach and identify candidate genes for further functional and therapeutic validation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.csbj.2025.10.032","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:48:56Z","timestamp":1760662136000},"page":"4476-4495","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"title":["Mathematical strategies for predicting resistant subpopulations from scRNAseq data of a PANC-1 3D tissue model: Insight into gemcitabine resistance and TGFB1-induced invasion and EMT"],"prefix":"10.34133","volume":"27","author":[{"given":"Aylin","family":"Caliskan","sequence":"first","affiliation":[{"name":"Department of Bioinformatics, Biocenter, University of W\u00fcrzburg, Am Hubland, W\u00fcrzburg 97074, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha A.W.","family":"Crouch","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Biocenter, University of W\u00fcrzburg, Am Hubland, W\u00fcrzburg 97074, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas Guillermo Nieves","family":"Pereira","sequence":"additional","affiliation":[{"name":"Department for Functional Materials in Medicine and Dentistry, University Hospital of W\u00fcrzburg, R\u00f6ntgenring 11, W\u00fcrzburg 97070, Germany"},{"name":"Institute for Molecular Medicine, Medical Faculty, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Stra\u00dfe 3a, Halle (Saale) 06120, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Dandekar","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Biocenter, University of W\u00fcrzburg, Am Hubland, W\u00fcrzburg 97074, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudrun","family":"Dandekar","sequence":"additional","affiliation":[{"name":"Department for Functional Materials in Medicine and Dentistry, University Hospital of W\u00fcrzburg, R\u00f6ntgenring 11, W\u00fcrzburg 97070, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Breitenbach","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Biocenter, University of W\u00fcrzburg, Am Hubland, W\u00fcrzburg 97074, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pan.2014.10.001"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"59","DOI":"10.21037\/cco.2017.12.01","article-title":"Pathologic classification of \u201cpancreatic cancers\u201d: current concepts and challenges","volume":"6","author":"Mostafa M.E.","year":"2017","unstructured":"Mostafa M.E. et al: Pathologic classification of \u201cpancreatic cancers\u201d: current concepts and challenges. Chin Clin Oncol 2017; 6: 59.","journal-title":"Chin Clin Oncol"},{"key":"e_1_3_4_4_2","unstructured":"Ferlay J. 2024. Global Cancer Observatory: Cancer Today 2024."},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"7048","DOI":"10.1038\/s41598-020-64068-3","article-title":"Survival of pancreatic cancer patients is negatively correlated with age at diagnosis: a population-based retrospective study","volume":"10","author":"Wang H.","year":"2020","unstructured":"Wang H. et al: Survival of pancreatic cancer patients is negatively correlated with age at diagnosis: a population-based retrospective study. Sci Rep 2020; 10: 7048.","journal-title":"Sci Rep"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.mpsur.2024.10.004","article-title":"Pancreatic cancer","volume":"43","author":"McGuigan M.-C.","year":"2025","unstructured":"McGuigan M.-C. and Jamieson N.B.: Pancreatic cancer. Surg (Oxf) 2025; 43: 26.","journal-title":"Surg (Oxf)"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2024.1930"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.01.259"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","DOI":"10.3390\/cancers9110157","article-title":"Pancreatic cancer chemoresistance to gemcitabine","volume":"9","author":"Amrutkar M.","year":"2017","unstructured":"Amrutkar M. and Gladhaug I.P.: Pancreatic cancer chemoresistance to gemcitabine. Cancers (Basel) 2017; 9.","journal-title":"Cancers (Basel)"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1011923"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)00172-8"},{"key":"e_1_3_4_12_2","first-page":"910","article-title":"2D and 3D cell cultures \u2013 a comparison of different types of cancer cell cultures","volume":"14","author":"Kapa\u0142czy\u0144ska M.","year":"2018","unstructured":"Kapa\u0142czy\u0144ska M. et al: 2D and 3D cell cultures \u2013 a comparison of different types of cancer cell cultures. Arch Med Sci 2018; 14: 910.","journal-title":"Arch Med Sci"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.04.018"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2016.3513"},{"key":"e_1_3_4_15_2","volume-title":"Transworld Research Network: Trivandrum (Indida)","author":"Whatcott C.J.","year":"2012","unstructured":"Whatcott C.J. et al: desmoplasia and chemoresistance in pancreatic cancer, in pancreatic cancer and tumor microenvironment. In: Transworld Research Network: Trivandrum (Indida). Edited by P. Grippo and H. Munshi. : 2012."},{"key":"e_1_3_4_16_2","first-page":"292","volume-title":"The prognostic value of stroma in pancreatic cancer in patients receiving adjuvant therapy","author":"Bever K.M.","year":"2015","unstructured":"Bever K.M. et al: The prognostic value of stroma in pancreatic cancer in patients receiving adjuvant therapy. : 2015: 292."},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.3389\/fonc.2020.576399","article-title":"Stroma-Targeting therapy in pancreatic cancer: one coin with two sides?","volume":"10","author":"Jiang B.","year":"2020","unstructured":"Jiang B. et al: Stroma-Targeting therapy in pancreatic cancer: one coin with two sides?. Front Oncol 2020; 10: 2020.","journal-title":"Front Oncol"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"5623","DOI":"10.1038\/s41467-021-25921-9","article-title":"Bioengineered 3D models of human pancreatic cancer recapitulate in vivo tumour biology","volume":"12","author":"Osuna de la Pe\u00f1a D.","year":"2021","unstructured":"Osuna de la Pe\u00f1a D. et al: Bioengineered 3D models of human pancreatic cancer recapitulate in vivo tumour biology. Nat Commun 2021; 12: 5623.","journal-title":"Nat Commun"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2022.08.015"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14092176"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12323"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"28","DOI":"10.3390\/cancers12010028","article-title":"Connecting cancer pathways to tumor engines: a stratification tool for colorectal cancer combining human in vitro tissue models with boolean in silico models","volume":"12","author":"Baur F.","year":"2020","unstructured":"Baur F. et al: Connecting cancer pathways to tumor engines: a stratification tool for colorectal cancer combining human in vitro tissue models with boolean in silico models. Cancers 2020; 12: 28.","journal-title":"Cancers"},{"key":"e_1_3_4_23_2","article-title":"Phenotype and genotype of pancreatic cancer cell lines","volume":"39","author":"Deer E.L.","year":"2010","unstructured":"Deer E.L. et al: Phenotype and genotype of pancreatic cancer cell lines. Pancreas 2010; 39.","journal-title":"Pancreas"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2025.09.028"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2023.06.002"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0302045","article-title":"An orchestra of machine learning methods reveals landmarks in single-cell data exemplified with aging fibroblasts","volume":"19","author":"Rasbach L.","year":"2024","unstructured":"Rasbach L. et al: An orchestra of machine learning methods reveals landmarks in single-cell data exemplified with aging fibroblasts. PLOS ONE 2024; 19: e0302045.","journal-title":"PLOS ONE"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2025.07.047"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-022-01075-1"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1089\/ten.2006.0388","article-title":"Engineered Liver-Like tissue on a capillarized matrix for applied research","volume":"13","author":"Linke K.","year":"2007","unstructured":"Linke K. et al: Engineered Liver-Like tissue on a capillarized matrix for applied research. Tissue Eng 2007; 13: 2699.","journal-title":"Tissue Eng"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtla.2025.102440"},{"key":"e_1_3_4_31_2","unstructured":"10x Genomics. Universal 3\u2032 and 5\u2032 Multiplex Gene Expression V(D)J & Feature Barcode Analysis with Cell Ranger multi. 2025; Available from: \u3008https:\/\/www.10xgenomics.com\/support\/software\/cell-ranger\/latest\/analysis\/running-pipelines\/cr-3p-multi#cellplex\u3009."},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3192"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01767-y"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2019.03.003"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty895"},{"key":"e_1_3_4_40_2","unstructured":"Kolde R. pheatmap: Pretty Heatmaps 2019 R package: \u3008https:\/\/CRAN.R-project.org\/package=pheatmap\u3009."},{"key":"e_1_3_4_41_2","unstructured":"Blighe K. S. Rana and M. Lewis EnhancedVolcano: Publication-ready volcano plots with enhanced colouring and labeling. 2022 R package: \u3008https:\/\/bioconductor.org\/packages\/release\/bioc\/html\/EnhancedVolcano.html\u3009."},{"key":"e_1_3_4_42_2","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"Clusterprofiler: an r package for comparing biological themes among gene clusters","volume":"16","author":"Yu G.","year":"2012","unstructured":"Yu G. et al: Clusterprofiler: an r package for comparing biological themes among gene clusters. OMICS A J Integr Biol 2012; 16: 284.","journal-title":"OMICS A J Integr Biol"},{"key":"e_1_3_4_43_2","article-title":"Clusterprofiler 4.0: a universal enrichment tool for interpreting omics data","volume":"2","author":"Wu T.","year":"2021","unstructured":"Wu T. et al: Clusterprofiler 4.0: a universal enrichment tool for interpreting omics data. Innovation 2021; 2.","journal-title":"Innovation"},{"key":"e_1_3_4_44_2","unstructured":"Carlson M. org.Hs.eg.db: Genome wide annotation for Human 2019."},{"key":"e_1_3_4_45_2","doi-asserted-by":"crossref","unstructured":"Dolgalev I. msigdbr: MSigDB Gene Sets for Multiple Organisms in a Tidy Data Format 2022.","DOI":"10.32614\/CRAN.package.babelgene"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1382-0"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01733-8"},{"key":"e_1_3_4_48_2","article-title":"GSEApy: a comprehensive package for performing gene set enrichment analysis in python","volume":"39","author":"Fang Z.","year":"2022","unstructured":"Fang Z., Liu X. and Peltz G.: GSEApy: a comprehensive package for performing gene set enrichment analysis in python. Bioinformatics 2022; 39.","journal-title":"Bioinformatics"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2015.12.004"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/75556"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp896"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.1.42"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn760"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1000"},{"key":"e_1_3_4_56_2","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1111\/cts.13563","article-title":"Analysis of a large cohort of pancreatic cancer transcriptomic profiles to reveal the strongest prognostic factors","volume":"16","author":"Posta M.","year":"2023","unstructured":"Posta M. and Gy\u0151rffy B.: Analysis of a large cohort of pancreatic cancer transcriptomic profiles to reveal the strongest prognostic factors. Clin Transl Sci 2023; 16: 1479.","journal-title":"Clin Transl Sci"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.1.207"},{"key":"e_1_3_4_58_2","article-title":"Integrated analysis of public datasets for the discovery and validation of survival-associated genes in solid tumors","volume":"5","author":"Gy\u0151rffy B.","year":"2024","unstructured":"Gy\u0151rffy B.: Integrated analysis of public datasets for the discovery and validation of survival-associated genes in solid tumors. Innovation 2024; 5.","journal-title":"Innovation"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16257"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-1289-1"},{"key":"e_1_3_4_61_2","article-title":"Single-Cell transcriptomics identifies a unique entity and signature markers of Transit-Amplifying cells in human corneal limbus","volume":"62","author":"Li J.-M.","year":"2021","unstructured":"Li J.-M. et al: Single-Cell transcriptomics identifies a unique entity and signature markers of Transit-Amplifying cells in human corneal limbus. Invest Ophthalmol Vis Sci 2021; 62. 36-36.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_3_4_62_2","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.bbrc.2021.02.117","article-title":"CDK1 inhibitor controls G2\/M phase transition and reverses DNA damage sensitivity","volume":"550","author":"Sunada S.","year":"2021","unstructured":"Sunada S. et al: CDK1 inhibitor controls G2\/M phase transition and reverses DNA damage sensitivity. Biochem Biophys Res Commun 2021; 550: 56.","journal-title":"Biochem Biophys Res Commun"},{"key":"e_1_3_4_63_2","doi-asserted-by":"crossref","first-page":"10871","DOI":"10.1038\/s41598-019-47416-w","article-title":"Enhanced morphological and functional differences of pancreatic cancer with epithelial or mesenchymal characteristics in 3D culture","volume":"9","author":"Shichi Y.","year":"2019","unstructured":"Shichi Y. et al: Enhanced morphological and functional differences of pancreatic cancer with epithelial or mesenchymal characteristics in 3D culture. Sci Rep 2019; 9: 10871.","journal-title":"Sci Rep"},{"key":"e_1_3_4_64_2","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.3389\/fonc.2020.00687","article-title":"TGF\u03b2 signaling increases net acid extrusion, proliferation and invasion in Panc-1 pancreatic cancer cells: SMAD4 dependence and link to Merlin\/NF2 signaling","volume":"10","author":"Malinda R.R.","year":"2020","unstructured":"Malinda R.R. et al: TGF\u03b2 signaling increases net acid extrusion, proliferation and invasion in Panc-1 pancreatic cancer cells: SMAD4 dependence and link to Merlin\/NF2 signaling. Front Oncol 2020; 10: 2020.","journal-title":"Front Oncol"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13246204"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32247"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12029-018-00195-5"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11605-021-05087-x"},{"key":"e_1_3_4_69_2","unstructured":"Peindl M. Refinement of 3D lung cancer models for automation and patient stratification with mode-of-action studies Weiterentwicklung von 3D Lungentumormodellen zur Automatisierung und Patienten-Stratifizierung mit Untersuchungen zur Wirkungsweise 2024."},{"key":"e_1_3_4_70_2","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/s41467-024-55330-7","article-title":"Spatial tumor immune heterogeneity facilitates subtype co-existence and therapy response in pancreatic cancer","volume":"16","author":"Klein L.","year":"2025","unstructured":"Klein L. et al: Spatial tumor immune heterogeneity facilitates subtype co-existence and therapy response in pancreatic cancer. Nat Commun 2025; 16: 335.","journal-title":"Nat Commun"},{"key":"e_1_3_4_71_2","doi-asserted-by":"crossref","DOI":"10.18632\/oncotarget.13212","article-title":"Inhibiting tumor necrosis factor-alpha diminishes desmoplasia and inflammation to overcome chemoresistance in pancreatic ductal adenocarcinoma","volume":"7","author":"Zhao X.","year":"2016","unstructured":"Zhao X. et al: Inhibiting tumor necrosis factor-alpha diminishes desmoplasia and inflammation to overcome chemoresistance in pancreatic ductal adenocarcinoma. Oncotarget 2016; 7.","journal-title":"Oncotarget"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.428920"},{"key":"e_1_3_4_73_2","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1158\/1541-7786.MCR-04-0117","article-title":"Transfection of keratin 18 gene in human breast cancer cells causes induction of adhesion proteins and dramatic regression of malignancy in vitro and in vivo","volume":"3","author":"B\u00fchler H.","year":"2005","unstructured":"B\u00fchler H. and Schaller G.: Transfection of keratin 18 gene in human breast cancer cells causes induction of adhesion proteins and dramatic regression of malignancy in vitro and in vivo. Mol Cancer Res 2005; 3: 365.","journal-title":"Mol Cancer Res"},{"key":"e_1_3_4_74_2","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.3892\/ijo.2016.3396","article-title":"Downregulation of cytokeratin 18 is associated with paclitaxel\u2011resistance and tumor aggressiveness in prostate cancer","volume":"48","author":"Yin B.","year":"2016","unstructured":"Yin B. et al: Downregulation of cytokeratin 18 is associated with paclitaxel\u2011resistance and tumor aggressiveness in prostate cancer. Int J Oncol 2016; 48: 1730.","journal-title":"Int J Oncol"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11162583"},{"key":"e_1_3_4_76_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1477-5956-7-3","article-title":"Identification of pancreatic cancer invasion-related proteins by proteomic analysis","volume":"7","author":"Walsh N.","year":"2009","unstructured":"Walsh N. et al: Identification of pancreatic cancer invasion-related proteins by proteomic analysis. Proteome Sci 2009; 7: 3.","journal-title":"Proteome Sci"},{"key":"e_1_3_4_77_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/eos.12666","article-title":"Expression of keratins 8, 18, and 19 in epithelia of atrophic oral lichen planus","volume":"128","author":"Schreurs O.","year":"2020","unstructured":"Schreurs O. et al: Expression of keratins 8, 18, and 19 in epithelia of atrophic oral lichen planus. Eur J Oral Sci 2020; 128: 7.","journal-title":"Eur J Oral Sci"},{"key":"e_1_3_4_78_2","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.amjms.2021.04.002","article-title":"PMEPA1 stimulates the proliferation, colony formation of pancreatic cancer cells via the MAPK signaling pathway","volume":"362","author":"Song M.","year":"2021","unstructured":"Song M. et al: PMEPA1 stimulates the proliferation, colony formation of pancreatic cancer cells via the MAPK signaling pathway. Am J Med Sci 2021; 362: 291.","journal-title":"Am J Med Sci"},{"key":"e_1_3_4_79_2","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1002\/ddr.21844","article-title":"PMEPA1 interference activates PTEN\/PI3K\/AKT, thereby inhibiting the proliferation, invasion and migration of pancreatic cancer cells and enhancing the sensitivity to gemcitabine and cisplatin","volume":"83","author":"Yang Y.","year":"2022","unstructured":"Yang Y. et al: PMEPA1 interference activates PTEN\/PI3K\/AKT, thereby inhibiting the proliferation, invasion and migration of pancreatic cancer cells and enhancing the sensitivity to gemcitabine and cisplatin. Drug Dev Res 2022; 83: 64.","journal-title":"Drug Dev Res"},{"key":"e_1_3_4_80_2","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1186\/s12885-022-09577-2","article-title":"The identification of liver metastasis- and prognosis-associated genes in pancreatic ductal adenocarcinoma","volume":"22","author":"Luan H.","year":"2022","unstructured":"Luan H. et al: The identification of liver metastasis- and prognosis-associated genes in pancreatic ductal adenocarcinoma. BMC Cancer 2022; 22: 463.","journal-title":"BMC Cancer"},{"key":"e_1_3_4_81_2","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2020-000676","article-title":"Inhibition of TGF-\u03b2-receptor signaling augments the antitumor function of ROR1-specific CAR T-cells against triple-negative breast cancer","volume":"8","author":"St\u00fcber T.","year":"2020","unstructured":"St\u00fcber T. et al: Inhibition of TGF-\u03b2-receptor signaling augments the antitumor function of ROR1-specific CAR T-cells against triple-negative breast cancer. J Immunother Cancer 2020; 8: e000676.","journal-title":"J Immunother Cancer"},{"key":"e_1_3_4_82_2","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.126345","article-title":"ROR1-CAR t cells are effective against lung and breast cancer in advanced microphysiologic 3D tumor models","volume":"4","author":"Wallstabe L.","year":"2019","unstructured":"Wallstabe L. et al: ROR1-CAR t cells are effective against lung and breast cancer in advanced microphysiologic 3D tumor models. JCI Insight 2019; 4.","journal-title":"JCI Insight"},{"key":"e_1_3_4_83_2","first-page":"289","article-title":"Modular micro-physiological human tumor\/tissue models based on decellularized tissue for improved preclinical testing","volume":"38","author":"K\u00fchnemundt J.","year":"2021","unstructured":"K\u00fchnemundt J. et al: Modular micro-physiological human tumor\/tissue models based on decellularized tissue for improved preclinical testing. ALTEX Altern Anim Exp 2021; 38: 289.","journal-title":"ALTEX Altern Anim Exp"},{"key":"e_1_3_4_84_2","article-title":"A combined 3D tissue engineered in Vitro\/In silico lung tumor model for predicting drug effectiveness in specific mutational backgrounds","author":"G\u00f6ttlich C.","year":"2016","unstructured":"G\u00f6ttlich C. et al: A combined 3D tissue engineered in Vitro\/In silico lung tumor model for predicting drug effectiveness in specific mutational backgrounds. JoVE 2016; : e53885.","journal-title":"JoVE"},{"key":"e_1_3_4_85_2","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.3748\/wjg.v12.i10.1597","article-title":"Effect of gemcitabine on the expression of apoptosis-related genes in human pancreatic cancer cells","volume":"12","author":"Jiang P.H.","year":"2006","unstructured":"Jiang P.H. et al: Effect of gemcitabine on the expression of apoptosis-related genes in human pancreatic cancer cells. World J Gastroenterol 2006; 12: 1597.","journal-title":"World J Gastroenterol"},{"key":"e_1_3_4_86_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adu2339"},{"key":"e_1_3_4_87_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1472-6750-3-11","article-title":"Characterization of mutations and loss of heterozygosity of p53 and K-ras2 in pancreatic cancer cell lines by immobilized polymerase chain reaction","volume":"3","author":"Butz J.","year":"2003","unstructured":"Butz J., Wickstrom E. and Edwards J.: Characterization of mutations and loss of heterozygosity of p53 and K-ras2 in pancreatic cancer cell lines by immobilized polymerase chain reaction. BMC Biotechnol 2003; 3: 11.","journal-title":"BMC Biotechnol"},{"key":"e_1_3_4_88_2","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.canlet.2019.04.036","article-title":"BIRC5 is a target for molecular imaging and detection of human pancreatic cancer","volume":"457","author":"Liu S.-H.","year":"2019","unstructured":"Liu S.-H. et al: BIRC5 is a target for molecular imaging and detection of human pancreatic cancer. Cancer Lett 2019; 457: 10.","journal-title":"Cancer Lett"},{"key":"e_1_3_4_89_2","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1186\/s12967-024-05528-6","article-title":"Insights into gemcitabine resistance in pancreatic cancer: association with metabolic reprogramming and TP53 pathogenicity in patient derived xenografts","volume":"22","author":"Konat\u00e9 M.M.","year":"2024","unstructured":"Konat\u00e9 M.M. et al: Insights into gemcitabine resistance in pancreatic cancer: association with metabolic reprogramming and TP53 pathogenicity in patient derived xenografts. J Transl Med 2024; 22: 733.","journal-title":"J Transl Med"},{"key":"e_1_3_4_90_2","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2200143119","article-title":"Calcium channel blockers potentiate gemcitabine chemotherapy in pancreatic cancer","volume":"119","author":"Principe D.R.","year":"2022","unstructured":"Principe D.R. et al: Calcium channel blockers potentiate gemcitabine chemotherapy in pancreatic cancer. Proc Natl Acad Sci 2022; 119: e2200143119.","journal-title":"Proc Natl Acad Sci"},{"key":"e_1_3_4_91_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14092057"},{"key":"e_1_3_4_92_2","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.3389\/fonc.2023.1230382","article-title":"Molecular profiling and specific targeting of gemcitabine-resistant subclones in heterogeneous pancreatic cancer cell populations","volume":"13","author":"F\u00e4rber B.","year":"2023","unstructured":"F\u00e4rber B. et al: Molecular profiling and specific targeting of gemcitabine-resistant subclones in heterogeneous pancreatic cancer cell populations. Front Oncol 2023; 13: 2023.","journal-title":"Front Oncol"},{"key":"e_1_3_4_93_2","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1186\/s13578-023-01118-z","article-title":"Post-translational modification of CDK1\u2013STAT3 signaling by fisetin suppresses pancreatic cancer stem cell properties","volume":"13","author":"Xu X.","year":"2023","unstructured":"Xu X. et al: Post-translational modification of CDK1\u2013STAT3 signaling by fisetin suppresses pancreatic cancer stem cell properties. Cell Biosci 2023; 13: 176.","journal-title":"Cell Biosci"},{"key":"e_1_3_4_94_2","doi-asserted-by":"crossref","first-page":"4389","DOI":"10.3390\/cancers13174389","article-title":"Cyclin dependent Kinase-1 (CDK-1) inhibition as a novel therapeutic strategy against pancreatic ductal adenocarcinoma (PDAC)","volume":"13","author":"Wijnen R.","year":"2021","unstructured":"Wijnen R. et al: Cyclin dependent Kinase-1 (CDK-1) inhibition as a novel therapeutic strategy against pancreatic ductal adenocarcinoma (PDAC). Cancers 2021; 13: 4389.","journal-title":"Cancers"},{"key":"e_1_3_4_95_2","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1038\/s41388-021-01664-1","article-title":"H2A.Z overexpression suppresses senescence and chemosensitivity in pancreatic ductal adenocarcinoma","volume":"40","author":"\u00c1vila-L\u00f3pez P.A.","year":"2021","unstructured":"\u00c1vila-L\u00f3pez P.A. et al: H2A.Z overexpression suppresses senescence and chemosensitivity in pancreatic ductal adenocarcinoma. Oncogene 2021; 40: 2065.","journal-title":"Oncogene"},{"key":"e_1_3_4_96_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2024.04.010"},{"key":"e_1_3_4_97_2","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.3389\/fbinf.2025.1528515","article-title":"Adaptive sampling methods facilitate the determination of reliable dataset sizes for evidence-based modeling","volume":"5","author":"Breitenbach T.","year":"2025","unstructured":"Breitenbach T. and Dandekar T.: Adaptive sampling methods facilitate the determination of reliable dataset sizes for evidence-based modeling. Front Bioinforma 2025; 5: 2025.","journal-title":"Front Bioinforma"}],"container-title":["Computational and Structural Biotechnology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2001037025004313?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2001037025004313?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/spj.science.org\/doi\/pdf\/10.1016\/j.csbj.2025.10.032","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T12:35:24Z","timestamp":1775219724000},"score":1,"resource":{"primary":{"URL":"https:\/\/spj.science.org\/doi\/10.1016\/j.csbj.2025.10.032"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,1]]},"references-count":96,"alternative-id":["10.1016\/j.csbj.2025.10.032"],"URL":"https:\/\/doi.org\/10.1016\/j.csbj.2025.10.032","relation":{},"ISSN":["2001-0370"],"issn-type":[{"value":"2001-0370","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Mathematical strategies for predicting resistant subpopulations from scRNAseq data of a PANC-1 3D tissue model: Insight into gemcitabine resistance and TGFB1-induced invasion and EMT","name":"articletitle","label":"Article Title"},{"value":"Computational and Structural Biotechnology Journal","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.csbj.2025.10.032","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.","name":"copyright","label":"Copyright"}]}}