{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:22:58Z","timestamp":1785435778717,"version":"3.56.0"},"reference-count":38,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science, Research, and Innovation Fund"},{"DOI":"10.13039\/501100004508","name":"Prince of Songkla University","doi-asserted-by":"crossref","award":["MED6701187S"],"award-info":[{"award-number":["MED6701187S"]}],"id":[{"id":"10.13039\/501100004508","id-type":"DOI","asserted-by":"crossref"}]},{"award":["MED6701187S"],"award-info":[{"award-number":["MED6701187S"]}],"id":[{"id":"https:\/\/ror.org\/0575ycz84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Erlotinib (ER) and gefitinib (GB) are frequently prescribed for patients with advanced lung adenocarcinoma (ADC). Although both ER and GB significantly extend median survival, several patients experience early disease relapse due to treatment resistance. This study aimed to identify common genes associated with acquired resistance to ER or GB. This integrative analysis of transcriptomic data identified differentially expressed genes by comparing sensitive PC-9 cells with ER-resistant (PC-9\/ER) or GB-resistant (PC-9\/GB) cell lines. A Venn diagram was used to identify common genes. Candidate genes were confirmed in our generated drug-resistant cell lines. After six months, the PC-9\/ER and PC-9\/GB cell lines exhibited 40.7-fold and 109.2-fold increases in resistance to ER and GB, respectively. Flow cytometric analysis demonstrated that both resistant cell lines were resistant to cell cycle arrest and apoptosis induced by ER or GB. Through integrated analysis, we found that two genes, KRT13 and CEACAM5, were up-regulated in both the PC-9\/ER and PC-9\/GB cell lines. The expression patterns of these two genes did not align with the transcriptome, with only CEACAM5 exhibiting consistent gene and protein expressions. Our findings indicate that CEACAM5 serves as a biomarker for predicting the response of patients to ER and GB treatments.<\/jats:p>","DOI":"10.3390\/ijms27073092","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T08:22:36Z","timestamp":1774858956000},"page":"3092","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5 as a Biomarker for Predicting Response to Erlotinib and Gefitinib in Lung Adenocarcinoma: An Integrative Analysis of Transcriptomic Data of PC-9 and Drug-Resistant PC-9 Cell Lines"],"prefix":"10.3390","volume":"27","author":[{"given":"Pritsana","family":"Raungrut","sequence":"first","affiliation":[{"name":"Division of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai 90112, Songkhla, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suchanan","family":"Tanyapattrapong","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai 90112, Songkhla, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8221-9454","authenticated-orcid":false,"given":"Saowanee","family":"Maungchanburi","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai 90112, Songkhla, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanyaphak","family":"Bumrungchoo","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai 90112, Songkhla, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102693","DOI":"10.1016\/j.canep.2024.102693","article-title":"Global burden of lung cancer in 2022 and projections to 2050: Incidence and mortality estimates from GLOBOCAN","volume":"93","author":"Zhou","year":"2024","journal-title":"Cancer Epidemiol."},{"key":"ref_2","unstructured":"American Cancer Society (2026, January 19). Facts & Figures 2025. Available online: https:\/\/www.cancer.org\/content\/dam\/cancer-org\/research\/cancer-facts-and-statistics\/annual-cancer-facts-and-figures\/2025\/2025-cancer-facts-and-figures-acs.pdf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1001\/jamaoncol.2021.4932","article-title":"Update of incidence, prevalence, survival, and initial treatment in patients with non-small cell lung cancer in the US","volume":"7","author":"Ganti","year":"2021","journal-title":"JAMA Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00595-017-1497-7","article-title":"Treatment of lung adenocarcinoma by molecular-targeted therapy and immunotherapy","volume":"48","author":"Saito","year":"2018","journal-title":"Surg. Today"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s13045-022-01311-6","article-title":"Emerging strategies to overcome resistance to third-generation EGFR inhibitors","volume":"15","author":"Shi","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zubair, T., and Bandyopadhyay, D. (2023). Small molecule EGFR inhibitors as anti-cancer agents: Discovery, mechanisms of action, and opportunities. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032651"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"433","DOI":"10.3109\/07357907.2012.666691","article-title":"Primary and acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer: An update","volume":"30","author":"Ayoola","year":"2012","journal-title":"Cancer Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1200\/JCO.2009.24.7049","article-title":"Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non\u2013small-cell lung cancer","volume":"28","author":"Jackman","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"610923","DOI":"10.3389\/fonc.2020.610923","article-title":"Concurrent genetic alterations and other biomarkers predict treatment efficacy of EGFR-TKIs in EGFR-mutant non-small cell lung cancer: A review","volume":"10","author":"Guo","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1200\/JCO.19.01154","article-title":"Gefitinib versus gefitinib plus pemetrexed and carboplatin chemotherapy in EGFR -mutated lung cancer","volume":"38","author":"Noronha","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8575","DOI":"10.2147\/OTT.S160358","article-title":"Afatinib versus gemcitabine\/cisplatin as first-line treatment for Chinese patients with advanced non-small cell lung cancer harboring EGFR mutations: Subgroup analysis of the LUX-Lung 6 trial","volume":"11","author":"Wu","year":"2018","journal-title":"OncoTargets Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e001011","DOI":"10.1136\/esmoopen-2020-001011","article-title":"Real-world clinical outcomes of first-generation and second-generation epidermal growth factor receptor tyrosine kinase inhibitors in a large cohort of European non-small-cell lung cancer patients","volume":"5","author":"Pluzanski","year":"2020","journal-title":"ESMO Open"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1158\/0008-5472.CAN-22-1002","article-title":"Elevated Methionine Flux Drives Pyroptosis Evasion in Persister Cancer Cells","volume":"83","author":"Berglund","year":"2023","journal-title":"Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s12935-019-0836-8","article-title":"Apatinib preferentially inhibits PC9 gefitinib-resistant cancer cells by inducing cell cycle arrest and inhibiting VEGFR signaling pathway","volume":"19","author":"Song","year":"2019","journal-title":"Cancer Cell Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/nm.4040","article-title":"Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition","volume":"22","author":"Hata","year":"2016","journal-title":"Nat. Med."},{"key":"ref_16","unstructured":"Moo-Young, M. (2011). 5.43\u2014In Vitro Micro-Tissue and -Organ Models for Toxicity Testing. Comprehensive Biotechnology, Academic Press. [2nd ed.]."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1037\/a0015914","article-title":"Integrative data analysis: The simultaneous analysis of multiple data sets","volume":"14","author":"Curran","year":"2009","journal-title":"Psychol. Methods"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5345","DOI":"10.1038\/s41467-024-49360-4","article-title":"Farnesyltransferase inhibition overcomes oncogene-addicted non-small cell lung cancer adaptive resistance to targeted therapies","volume":"15","author":"Figarol","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"109448","DOI":"10.1016\/j.isci.2024.109448","article-title":"Systematic omics analysis identifies CCR6 as a therapeutic target for overcoming cancer resistance to EGFR inhibitors","volume":"27","author":"Kwon","year":"2024","journal-title":"iScience"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nrg2484","article-title":"RNA-Seq: A revolutionary tool for transcriptomics","volume":"10","author":"Wang","year":"2009","journal-title":"Nat. Rev. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100043","DOI":"10.1016\/j.bioflm.2021.100043","article-title":"Do results obtained with RNA-sequencing require independent verification?","volume":"3","author":"Coenye","year":"2021","journal-title":"Biofilm"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.cell.2016.08.056","article-title":"Editing DNA methylation in the mammalian genome","volume":"167","author":"Liu","year":"2016","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nrg3185","article-title":"Insights into the regulation of protein abundance from proteomic and transcriptomic analyses","volume":"13","author":"Vogel","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0092-8674(89)90970-7","article-title":"Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule","volume":"57","author":"Benchimol","year":"1989","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1159\/000217555","article-title":"Immunohistochemistry of carcino-embryonic antigen in the embryo, fetus and adult","volume":"9","author":"Nap","year":"1988","journal-title":"Tumour Biol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Jansen, K., Kornfeld, L., Lennartz, M., Dwertmann Rico, S., Kind, S., Reiswich, V., Viehweger, F., Bawahab, A.A., Fraune, C., and Gorbokon, N. (2024). Carcinoembryonic antigen expression in human tumors: A tissue microarray study on 13,725 tumors. Cancers, 16.","DOI":"10.3390\/cancers16234052"},{"key":"ref_27","first-page":"11683","article-title":"Tumor markers CA19-9, CA242 and CEA in the diagnosis of pancreatic cancer: A meta-analysis","volume":"8","author":"Zhang","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13227","DOI":"10.1038\/s41598-024-64297-w","article-title":"Simultaneous screening of overexpressed genes in breast cancer for oncogenic drivers and tumor dependencies","volume":"14","author":"Mofunanya","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1080\/00365521.2022.2106152","article-title":"Synergistic diagnostic value of circulating tumor cells and tumor markers CEA\/CA19-9 in colorectal cancer","volume":"58","author":"Cai","year":"2023","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_30","first-page":"CD011134","article-title":"Blood CEA levels for detecting recurrent colorectal cancer","volume":"2015","author":"Nicholson","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3002","DOI":"10.1200\/JCO.2017.35.15_suppl.3002","article-title":"Phase Ia and Ib studies of the novel carcinoembryonic antigen (CEA) T-cell bispecific (CEA CD3 TCB) antibody as a single agent and in combination with atezolizumab: Preliminary efficacy and safety in patients with metastatic colorectal cancer (mCRC)","volume":"35","author":"Tabernero","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"300060520959478","DOI":"10.1177\/0300060520959478","article-title":"CEACAM5 stimulates the progression of non-small-cell lung cancer by promoting cell proliferation and migration","volume":"48","author":"Zhang","year":"2020","journal-title":"J. Int. Med. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.athoracsur.2022.05.019","article-title":"Glycoprotein receptor CEACAM5-targeted intraoperative molecular imaging tracer in non-small cell lung cancer","volume":"116","author":"Azari","year":"2023","journal-title":"Ann. Thorac. Surg."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kim, Y.J., Li, W., Zhelev, D.V., Mellors, J.W., Dimitrov, D.S., and Baek, D.S. (2023). Chimeric antigen receptor-T cells are effective against CEACAM5 expressing non-small cell lung cancer cells resistant to antibody-drug conjugates. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1124039"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.critrevonc.2013.08.003","article-title":"Are erlotinib and gefitinib interchangeable, opposite or complementary for non-small cell lung cancer treatment? Biological, pharmacological and clinical aspects","volume":"89","author":"Bronte","year":"2014","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1093\/bioinformatics\/btm254","article-title":"GEOquery: A bridge between the Gene Expression Omnibus (GEO) and BioConductor","volume":"23","author":"Davis","year":"2007","journal-title":"Bioinformatics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"D362","DOI":"10.1093\/nar\/gkw937","article-title":"The STRING database in 2017: Quality-controlled protein-protein association networks, made broadly accessible","volume":"45","author":"Szklarczyk","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"13951","DOI":"10.3390\/cimb46120834","article-title":"Transcriptomic Profiling of Carboplatin- and Paclitaxel-Resistant Lung Adenocarcinoma Cells Reveals CSF3 as a Potential Biomarker for the Carboplatin Plus Paclitaxel Doublet Regimens","volume":"46","author":"Raungrut","year":"2024","journal-title":"Curr. Issues Mol. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/7\/3092\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T15:49:37Z","timestamp":1775058577000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/7\/3092"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,28]]},"references-count":38,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27073092"],"URL":"https:\/\/doi.org\/10.3390\/ijms27073092","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,28]]}}}