{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T01:39:26Z","timestamp":1773365966291,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Research Projects Coordination Unit of Istanbul University Rectorate","award":["TSA-2020-TSA-37036"],"award-info":[{"award-number":["TSA-2020-TSA-37036"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>To investigate whether pretreatment serum endocan, platelet-derived growth factor (PDGF)-CC, and -DD levels are elevated in metastatic colorectal cancer (mCRC) patients compared to healthy controls, and to assess their independent associations with chemotherapy response and survival, along with their comparative predictive performance. Adult patients with mCRC receiving systemic chemotherapy combined with an anti-angiogenic agent (bevacizumab or aflibercept) were prospectively enrolled, along with healthy controls. Pretreatment serum samples were collected prior to therapy initiation. Endocan, PDGF-CC, and PDGF-DD levels were measured in duplicate using enzyme-linked immunosorbent assay. Treatment response was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and categorized as responders (complete or partial response) and non-responders (stable or progressive disease). Progression-free survival (PFS) and overall survival (OS) were recorded. Median serum levels of endocan (405.5 vs. 269.0 pg\/mL), PDGF-DD (499.9 vs. 315.1 pg\/mL), and PDGF-CC (2330 vs. 1118 pg\/mL) were significantly higher in the mCRC group compared to controls (p &lt; 0.001). In multivariable logistic regression, all three biomarkers were independently associated with non-response to chemotherapy [Odds ratio (ORs): 1.10 for endocan, 1.05 for PDGF-DD, 1.05 for PDGF-CC; all p &lt; 0.05]. For disease progression, Cox regression showed that higher levels of endocan [Hazard ratio (HR) = 1.04], PDGF-DD (HR = 1.03), and PDGF-CC (HR = 1.04) were significant predictors (all p &lt; 0.01). Similar associations were observed for overall mortality (HR = 1.04, 1.02, and 1.02, respectively; all p &lt; 0.05). Endocan, PDGF-DD, and PDGF-CC are elevated in mCRC and independently predict poor treatment response and adverse survival outcomes, highlighting their potential as prognostic biomarkers.<\/jats:p>","DOI":"10.3390\/ijms27062600","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T13:12:24Z","timestamp":1773321144000},"page":"2600","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic Role of Endocan and Platelet-Derived Growth Factor Isoforms in Metastatic Colorectal Cancer"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6402-4445","authenticated-orcid":false,"given":"An\u0131l","family":"Y\u0131ld\u0131z","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Ba\u015fak\u015fehir \u00c7am and Sakura City Hospital, \u0130stanbul 34480, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melin Aydan","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Istanbul University Oncology Institute, \u0130stanbul 34093, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5068-6472","authenticated-orcid":false,"given":"Abdulmunir","family":"Azizy","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Istanbul University Oncology Institute, \u0130stanbul 34093, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simay","family":"\u00c7okgezer","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Istanbul University Oncology Institute, \u0130stanbul 34093, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bedirhan","family":"Ulufer","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Istanbul University Oncology Institute, \u0130stanbul 34093, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7858-1584","authenticated-orcid":false,"given":"Hilal O\u011fuz","family":"Soydin\u00e7","sequence":"additional","affiliation":[{"name":"Department of Basic Oncology, Istanbul University Oncology Institute, \u0130stanbul 34093, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanem","family":"Karabulut","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Istanbul University Oncology Institute, \u0130stanbul 34093, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Didem","family":"Ta\u015ftekin","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Istanbul University Oncology Institute, \u0130stanbul 34093, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Burak","family":"\u015eakar","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Istanbul University Oncology Institute, \u0130stanbul 34093, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5790-7066","authenticated-orcid":false,"given":"Naziye","family":"Ak","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Istanbul University Oncology Institute, \u0130stanbul 34093, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wu, S., Zhang, Y., Lin, Z., and Wei, M. (2025). Global burden of colorectal cancer in 2022 and projections to 2050: Incidence and mortality estimates from GLOBOCAN. BMC Cancer, 25.","DOI":"10.1186\/s12885-025-15138-0"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Pecsi, B., and Mangel, L.C. (2024). The Real-Life Impact of Primary Tumor Resection of Synchronous Metastatic Colorectal Cancer-From a Clinical Oncologic Point of View. Cancers, 16.","DOI":"10.3390\/cancers16081460"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Cainap, C., Bochis, O.V., Vlad, C., Popita, R., Achimas-Cadariu, P., Havasi, A., Vidrean, A., Dranca, A., Piciu, A., and Constantin, A.-M. (2021). Doubling the Dose of Bevacizumab Beyond Progression in Metastatic Colorectal Cancer-the Experience of a Tertiary Cancer Center. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.487316"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Lavacchi, D., Roviello, G., Giommoni, E., Dreoni, L., Derio, S., Brugia, M., Amedei, A., Pillozzi, S., and Antonuzzo, L. (2021). Aflibercept Plus FOLFIRI as Second-Line Treatment for Metastatic Colorectal Cancer: A Single-Institution Real-Life Experience. Cancers, 13.","DOI":"10.3390\/cancers13153863"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1038\/s41598-017-01420-0","article-title":"Circulating VEGF and eNOS variations as predictors of outcome in metastatic colorectal cancer patients receiving bevacizumab","volume":"7","author":"Marisi","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/s41392-023-01460-1","article-title":"Angiogenic signaling pathways and anti-angiogenic therapy for cancer","volume":"8","author":"Liu","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5519","DOI":"10.4238\/2015.May.25.3","article-title":"Serum level of endothelial cell-specific molecule-1 and prognosis of colorectal cancer","volume":"14","author":"Jiang","year":"2015","journal-title":"Genet. Mol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s13643-025-02858-4","article-title":"The predictive value of endocan as a novel biomarker: An umbrella study on meta-analyses","volume":"14","author":"Nayak","year":"2025","journal-title":"Syst. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"188672","DOI":"10.1016\/j.bbcan.2021.188672","article-title":"Proteoglycan Endocan: A multifaceted therapeutic target in Cancer","volume":"1877","author":"Pan","year":"2022","journal-title":"Biochim. Biophys. Acta (BBA)-Rev. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1007\/s10555-024-10194-7","article-title":"Functional and clinical roles of stromal PDGF receptors in tumor biology","volume":"43","author":"Strell","year":"2024","journal-title":"Cancer Metastasis Rev."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Li, H., Zeitelhofer, M., Nilsson, I., Liu, X., Allan, L., Gloria, B., Perani, A., Murone, C., Catimel, B., and Neville, A.M. (2018). Development of monoclonal anti-PDGF-CC antibodies as tools for investigating human tissue expression and for blocking PDGF-CC induced PDGFRalpha signalling in vivo. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0201089"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1007\/s00432-014-1723-2","article-title":"Gastric cancer-derived MSC-secreted PDGF-DD promotes gastric cancer progression","volume":"140","author":"Huang","year":"2014","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S1451","DOI":"10.1016\/j.annonc.2022.10.091","article-title":"59P Platelet-derived growth factor (PDGF)-CC serum as clinical outcome predictor after six cycles of chemotherapy in colorectal cancer at RSMH Palembang","volume":"33","author":"Sundarita","year":"2022","journal-title":"Ann. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3138","DOI":"10.1158\/1538-7445.AM2020-3138","article-title":"Colorectal cancer is associated with elevated plasma levels of soluble platelet-derived growth factor-dd (PDGF-DD) compared to plasma levels of benign colon disease patients","volume":"80","author":"Mudiyanselage","year":"2020","journal-title":"Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1080\/07357907.2019.1576191","article-title":"Possible Role and Therapeutic Target of PDGF-D Signalling in Colorectal Cancer","volume":"37","author":"Olsen","year":"2019","journal-title":"Cancer Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1111\/j.1349-7006.2010.01665.x","article-title":"Identification of endothelial cell-specific molecule-1 as a potential serum marker for colorectal cancer","volume":"101","author":"Ji","year":"2010","journal-title":"Cancer Sci."},{"key":"ref_17","first-page":"2920","article-title":"ESM1 promotes angiogenesis in colorectal cancer by activating PI3K\/Akt\/mTOR pathway, thus accelerating tumor progression","volume":"15","author":"Yang","year":"2023","journal-title":"Aging"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s00018-024-05411-z","article-title":"Endothelial cell heterogeneity in colorectal cancer: Tip cells drive angiogenesis","volume":"81","author":"Xie","year":"2024","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/s41467-024-55487-1","article-title":"Endothelial-secreted Endocan activates PDGFRA and regulates vascularity and spatial phenotype in glioblastoma","volume":"16","author":"Bastola","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5659","DOI":"10.2147\/CMAR.S181570","article-title":"IL-8 and thrombospondin-1 as prognostic markers in patients with metastatic colorectal cancer receiving bevacizumab","volume":"10","author":"Marisi","year":"2018","journal-title":"Cancer Manag. Res."},{"key":"ref_21","first-page":"1193","article-title":"Is there a correlation between peripheral blood expression of angiogenic transcriptional factors\/receptors and colorectal cancer","volume":"20","author":"Balacescu","year":"2015","journal-title":"J. BUON"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11","DOI":"10.4236\/jct.2014.51002","article-title":"Clinical significance of platelet-derived growth factor-C expression in colorectal cancer","volume":"5","author":"Yamauchi","year":"2014","journal-title":"J. Cancer Ther."},{"key":"ref_23","first-page":"1573","article-title":"Platelet-derived growth factor-D promotes colorectal cancer cell migration, invasion and proliferation by regulating Notch1 and matrix metalloproteinase-9","volume":"15","author":"Jiang","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Balalis, D., Tsakogiannis, D., Kalogera, E., Kokkali, S., Tripodaki, E., Ardavanis, A., Manatakis, D., Dimas, D., Koufopoulos, N., and Fostira, F. (2022). Serum Concentration of Selected Angiogenesis-Related Molecules Differs among Molecular Subtypes, Body Mass Index and Menopausal Status in Breast Cancer Patients. J. Clin. Med., 11.","DOI":"10.3390\/jcm11144079"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5940049","DOI":"10.1155\/2022\/5940049","article-title":"The PDGF Family Is Associated with Activated Tumor Stroma and Poor Prognosis in Ovarian Cancer","volume":"2022","author":"Li","year":"2022","journal-title":"Dis. Markers"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1158\/0008-5472.CAN-22-1890","article-title":"Stromal Reprogramming through Dual PDGFRalpha\/beta Blockade Boosts the Efficacy of Anti-PD-1 Immunotherapy in Fibrotic Tumors","volume":"83","author":"Akiyama","year":"2023","journal-title":"Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1610350","DOI":"10.3389\/pore.2022.1610350","article-title":"Cancer-Associated Stromal Fibroblast-Derived Transcriptomes Predict Poor Clinical Outcomes and Immunosuppression in Colon Cancer","volume":"28","author":"Wang","year":"2022","journal-title":"Pathol. Oncol. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6252","DOI":"10.1021\/acs.jproteome.5c00785","article-title":"Plasma Proteomic Profiling of Colorectal Cancer: Insights from Minimally Invasive Surgical Cohorts","volume":"24","author":"Yan","year":"2025","journal-title":"J. Proteome Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"572","DOI":"10.3390\/ph3030572","article-title":"Platelet-Derived Growth Factor (PDGF)\/PDGF Receptors (PDGFR) Axis as Target for Antitumor and Antiangiogenic Therapy","volume":"3","author":"Raica","year":"2010","journal-title":"Pharmaceuticals"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"9961","DOI":"10.18632\/oncotarget.14283","article-title":"PDGF-D promotes cell growth, aggressiveness, angiogenesis and EMT transformation of colorectal cancer by activation of Notch1\/Twist1 pathway","volume":"8","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"216266","DOI":"10.1016\/j.canlet.2023.216266","article-title":"Reversible promoter demethylation of PDGFD confers gemcitabine resistance through STAT3 activation and RRM1 upregulation","volume":"567","author":"Qin","year":"2023","journal-title":"Cancer Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.bbrc.2023.07.054","article-title":"Positive regulatory loop of platelet-derived growth factor DD-induced STAT3 activation is associated with poor prognosis in advanced urothelial carcinoma","volume":"676","author":"Ando","year":"2023","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.18632\/oncotarget.28281","article-title":"Platelet-derived growth factor (PDGF) cross-signaling via non-corresponding receptors indicates bypassed signaling in colorectal cancer","volume":"13","author":"Moench","year":"2022","journal-title":"Oncotarget"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Filippelli, A., Del Gaudio, C., Simonis, V., Ciccone, V., Spini, A., and Donnini, S. (2022). Scoping Review on Platelets and Tumor Angiogenesis: Do We Need More Evidence or Better Analysis?. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113401"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"29500","DOI":"10.1038\/s41598-025-15309-w","article-title":"Combined preoperative platelet-albumin ratio and cancer inflammation prognostic index predicts prognosis in colorectal cancer: A retrospective study","volume":"15","author":"Wang","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wang, K., Zhang, B., Li, K., Zhang, Z., Zeng, X., Guan, J.-M., Aldridge, R., Whitmore, E., Pan, Y., and Lau, L.Y. (2025). Novel immune-nutritional prognostic ratio predicts long-term survival in stage I-III colorectal cancer. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1694587"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e71317","DOI":"10.1002\/cam4.71317","article-title":"Metabolic Reprogramming in Lung Cancer: Hallmarks, Mechanisms, and Targeted Strategies to Overcome Immune Resistance","volume":"14","author":"Chen","year":"2025","journal-title":"Cancer Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1245\/s10434-010-0985-4","article-title":"The American Joint Committee on Cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM","volume":"17","author":"Edge","year":"2010","journal-title":"Ann. Surg. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"558","DOI":"10.4097\/kja.19087","article-title":"Multicollinearity and misleading statistical results","volume":"72","author":"Kim","year":"2019","journal-title":"Korean J. Anesthesiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/6\/2600\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T13:14:31Z","timestamp":1773321271000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/6\/2600"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,12]]},"references-count":39,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ijms27062600"],"URL":"https:\/\/doi.org\/10.3390\/ijms27062600","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,12]]}}}