{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T01:35:33Z","timestamp":1778636133944,"version":"3.51.4"},"reference-count":76,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T00:00:00Z","timestamp":1614211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004700","name":"Taipei Medical University","doi-asserted-by":"publisher","award":["102CM-TMU-03"],"award-info":[{"award-number":["102CM-TMU-03"]}],"id":[{"id":"10.13039\/501100004700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010425","name":"Tri-Service General Hospital","doi-asserted-by":"publisher","award":["TSGH-C03-110022"],"award-info":[{"award-number":["TSGH-C03-110022"]}],"id":[{"id":"10.13039\/501100010425","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010425","name":"Tri-Service General Hospital","doi-asserted-by":"publisher","award":["TSGH-D110079"],"award-info":[{"award-number":["TSGH-D110079"]}],"id":[{"id":"10.13039\/501100010425","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Signal transducer and activator of transcription 3 (STAT3)\/Cyclin-dependent kinases are multifunctional proteins that play an important implicative role in cancer initiations, progression, drug resistance, and metastasis, and has been extensively explored in cancer therapy. However, the genetic alterations of STAT3\/CDK2\/4\/6 and its role in predicting immune infiltration and immunotherapeutic response are yet to be well exploited. In this study, we use in silico methods to analyze differential expression, prognostic value, genetic and epigenetic alterations, association with tumor-infiltrating immune cells, and cancer-associated fibroblast (CAF) infiltrations of STAT3\/CDK2\/4\/6 in multiple cancer types. Our results revealed that the expression of STAT3\/CDK2\/4\/6 was altered in various cancers and is associated with poor overall and disease-free survival of the cohorts. Moreover, genetic alterations in STAT3\/CDK2\/4\/6 co-occurred with a number of other genetic alterations and are associated with poorer prognoses of the cohorts. The protein-protein interaction (PPI) network analysis suggests CDK2\/4\/6\/STAT3 may directly interact with factors that promote tumorigenesis and immune response. We found that STAT3\/CDK2\/4\/6 expressions were associated with infiltrations of CAF and the various immune cells in multiple cancers and it\u2019s associated with poor response to immunotherapy. Collectively, our study suggested that STAT3\/CDK2\/4\/6 are important onco-immune signatures that play central roles in tumor immune invasion, poor prognoses and, immune therapy response. Findings from the present study may therefore be clinically useful in prognosis assessment and follow-up management of immunotherapy.<\/jats:p>","DOI":"10.3390\/cancers13050954","type":"journal-article","created":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T21:16:53Z","timestamp":1614287813000},"page":"954","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Multi-Omics Data Analysis of Gene Expressions and Alterations, Cancer-Associated Fibroblast and Immune Infiltrations, Reveals the Onco-Immune Prognostic Relevance of STAT3\/CDK2\/4\/6 in Human Malignancies"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0676-5875","authenticated-orcid":false,"given":"Bashir","family":"Lawal","sequence":"first","affiliation":[{"name":"PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, and Academia Sinica, Taipei 11031, Taiwan"},{"name":"Graduate Institute for Cancer Biology &amp; Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Ching","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Chi-Mei Foundation Medical Center, Tainan 71004, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jih-Chin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, 325 Cheng-Kung Road Section 2, Taipei 114, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanios","family":"Bekaii-Saab","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Mayo Clinic Arizona, Scottsdale, AZ 85054, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0178-6530","authenticated-orcid":false,"given":"Alexander","family":"Wu","sequence":"additional","affiliation":[{"name":"The PhD Program of Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Clinical Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"National Defense Medical Center, Graduate Institute of Medical Sciences, Taipei 114, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching-Liang","family":"Ho","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mandal, M., Sahoo, S.K., Patra, P., Mallik, S., and Zhao, Z. 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