{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T13:55:42Z","timestamp":1788184542141,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T00:00:00Z","timestamp":1728259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Youth Interdisciplinary Special Fund of Zhongnan Hospital of Wuhan University","award":["ZNQNJC2023009"],"award-info":[{"award-number":["ZNQNJC2023009"]}]},{"name":"Youth Interdisciplinary Special Fund of Zhongnan Hospital of Wuhan University","award":["2022CFB616"],"award-info":[{"award-number":["2022CFB616"]}]},{"name":"Youth Interdisciplinary Special Fund of Zhongnan Hospital of Wuhan University","award":["CXPJJH122006-1014"],"award-info":[{"award-number":["CXPJJH122006-1014"]}]},{"DOI":"10.13039\/501100003819","name":"Hubei Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["ZNQNJC2023009"],"award-info":[{"award-number":["ZNQNJC2023009"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003819","name":"Hubei Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["2022CFB616"],"award-info":[{"award-number":["2022CFB616"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003819","name":"Hubei Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["CXPJJH122006-1014"],"award-info":[{"award-number":["CXPJJH122006-1014"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chen Xiao-Ping Foundation for the Development of Science and Technology of Hubei Province","award":["ZNQNJC2023009"],"award-info":[{"award-number":["ZNQNJC2023009"]}]},{"name":"Chen Xiao-Ping Foundation for the Development of Science and Technology of Hubei Province","award":["2022CFB616"],"award-info":[{"award-number":["2022CFB616"]}]},{"name":"Chen Xiao-Ping Foundation for the Development of Science and Technology of Hubei Province","award":["CXPJJH122006-1014"],"award-info":[{"award-number":["CXPJJH122006-1014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Depressive disorder contributes to the initiation and prognosis of patients with cancer, but the interaction between cancer and depressive disorder remains unclear. We generated a gastric adenocarcinoma patient-derived xenograft mice model, treated with chronic unpredictable mild stimulation. Based on the RNA-sequence from the mouse model, patient data from TCGA, and MDD-related (major depressive disorder) genes from the GEO database, 56 hub genes were identified by the intersection of differential expression genes from the three datasets. Molecular subtypes and a prognostic signature were generated based on the 56 genes. A depressive mouse model was constructed to test the key changes in the signatures. The signature was constructed based on the NDUFA4L2, ANKRD45, and AQP3 genes. Patients with high risk-score had a worse overall survival than the patients with low scores, consistent with the results from the two GEO cohorts. The comprehensive results showed that a higher risk-score was correlated with higher levels of tumor immune exclusion, higher infiltration of M0 macrophages, M2 macrophages, and neutrophils, higher angiogenetic activities, and more enriched epithelial\u2013mesenchymal transition signaling pathways. A higher risk score was correlated to a higher MDD score, elevated MDD-related cytokines, and the dysfunction of neurogenesis-related genes, and parts of these changes showed similar trends in the animal model. With the Genomics of Drug Sensitivity in Cancer database, we found that the gastric adenocarcinoma patients with high risk-score may be sensitive to Pazopanib, XMD8.85, Midostaurin, HG.6.64.1, Elesclomol, Linifanib, AP.24534, Roscovitine, Cytarabine, and Axitinib. The gene signature consisting of the NDUFA4L2, ANKRD45, and AQP3 genes is a promising biomarker to distinguish the prognosis, the molecular and immune characteristics, the depressive risk, and the therapy candidates for gastric adenocarcinoma patients.<\/jats:p>","DOI":"10.3390\/ijms251910776","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T08:35:23Z","timestamp":1728290123000},"page":"10776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Development and Validation of a Comprehensive Prognostic and Depression Risk Index for Gastric Adenocarcinoma"],"prefix":"10.3390","volume":"25","author":[{"given":"Sheng","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China"},{"name":"Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China"},{"name":"Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China"},{"name":"Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China"},{"name":"Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China"},{"name":"Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China"},{"name":"Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4293-6205","authenticated-orcid":false,"given":"Sachiyo","family":"Nomura","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7205-4663","authenticated-orcid":false,"given":"Yongchang","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China"},{"name":"Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China"},{"name":"Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianhe","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China"},{"name":"Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China"},{"name":"Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1038\/s41380-019-0595-x","article-title":"Depression and anxiety in relation to cancer incidence and mortality: A systematic review and meta-analysis of cohort studies","volume":"25","author":"Wang","year":"2020","journal-title":"Mol. 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