{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:01:24Z","timestamp":1788314484204,"version":"build-2803163510"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T00:00:00Z","timestamp":1734393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["12075162 72274152 12101107"],"award-info":[{"award-number":["12075162 72274152 12101107"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018542","name":"Natural Science Foundation of Sichuan Province","doi-asserted-by":"publisher","award":["2024NSFSC1395 2024NSFSC0040"],"award-info":[{"award-number":["2024NSFSC1395 2024NSFSC0040"]}],"id":[{"id":"10.13039\/501100018542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>In a randomized clinical controlled trial (PA.3) conducted by the Canadian Cancer Trials Group, the effects of gemcitabine combined with the targeted drug erlotinib (GEM-E) <jats:italic>versus<\/jats:italic> gemcitabine alone (GEM) on patients with unresectable, locally advanced, or metastatic pancreatic cancer were studied. This trial statistically demonstrated that the GEM-E combination therapy moderately improves overall survival (OS) of patients. However, real-world analysis suggested that GEM-E for pancreatic cancer was not more effective than GEM. The heterogeneity in outcomes or treatment effect exist. Thus, we tried to find predictive biomarkers to identifying the heterogeneous patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Of the 569 eligible patients, 480 patients had plasma samples. Univariate and multivariate Cox proportional hazards model were used to identify baseline characteristics related to OS, and a risk adjusted Exponentially Weighted Moving Average (EWMA) control chart based on a weighted score test from the Cox model was constructed to monitor patients\u2019 survival risk. Maximally selected rank statistics were constructed to identifying the predictive biomarkers, in addition, a risk adjusted control chart based on a weighted score test from the Cox model was constructed to validating the predictive biomarkers, discover the patients who sensitive to the GEM-E or GEM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three baseline characteristics (ECOG performance status, extent of disease, and pain intensity) were identified related to prognosis. A risk-adjusted EWMA control chart was constructed and showed that GEM-E did improve OS in a few patients. Three biomarkers (BMP2, CXCL6, and HER2) were identified as predictive biomarkers based on maximum selected rank test, and using the risk-adjusted EWMA control chart to validate the reality and discover some patients who are sensitive to the GEM-E therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In reality, GEM-E has not shown a significant advantage over GEM in the treatment of pancreatic cancer. However, we discovered some patients who are sensitive to the GEM-E therapy based on the predictive biomarkers, which suggest that the predictive biomarkers provide ideas for personalized medicine in pancreatic cancer.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fgene.2024.1497254","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T06:25:43Z","timestamp":1734416743000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification and validation the predictive biomarkers based on risk-adjusted control chart in gemcitabine with or without erlotinib for pancreatic cancer therapy"],"prefix":"10.3389","volume":"15","author":[{"given":"Aijun","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixing","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s40364-020-00209-0","article-title":"Predictive biomarkers for cancer immunotherapy with immune checkpoint inhibitors","volume":"8","author":"Bai","year":"2020","journal-title":"Biomark. 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