PMID- 34368124 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210810 IS - 2296-634X (Print) IS - 2296-634X (Electronic) IS - 2296-634X (Linking) VI - 9 DP - 2021 TI - Identification of a Novel Immune Landscape Signature for Predicting Prognosis and Response of Endometrial Carcinoma to Immunotherapy and Chemotherapy. PG - 671736 LID - 10.3389/fcell.2021.671736 [doi] LID - 671736 AB - Uterine Corpus Endometrial Carcinoma (UCEC) is the most common gynecological cancer. Here, we have investigated the significance of immune-related genes in predicting the prognosis and response of UCEC patients to immunotherapy and chemotherapy. Based on the Cancer Genome Atlas (TCGA) database, the single-sample gene-set enrichment analysis (ssGSEA) scores was utilized to obtain enrichment of 29 immune signatures. Univariate, multivariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to generate an immune-related prognostic signature (IRPS). The biological functions of IRPS-associated genes were evaluated using GSEA, Tumor Immune Estimation Resource (TIMER) Database analysis, Mutation analysis, Immunophenoscore (IPS) analysis, Gene Expression Profiling Interactive Analysis (GEPIA), Genomics of Drug Sensitivity in Cancer (GDSC) and Immune Cell Abundance Identifier (ImmuCellAI). Potential small molecule drugs for UCEC were predicted using the connectivity map (Cmap). The mRNA and protein expression levels of IRPS-associated genes were tested via quantitative real-time PCR (qPCR) and immunohistology. Two immune-related genes (CCL13 and KLRC1) were identified to construct the IRPS. Both genes were related to the prognosis of UCEC patients (P < 0.05). The IRPS could distinguish patients with different prognosis and was closely associated with the infiltration of several types of immune cells. Our findings showed that patients with low IRPS benefited more from immunotherapy and developed stronger response to several chemotherapies, which was also confirmed by the results of ImmuCellAI. Finally, we identified three small molecular drugs that might improve the prognosis of patients with high IRPS. IRPS can be utilized to predict the prognosis of UCEC patients and provide valuable information about their therapeutic response to immunotherapy and chemotherapy. CI - Copyright (c) 2021 Liu, Wang, Mei, Nie and Zhang. FAU - Liu, Jinhui AU - Liu J AD - Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Wang, Yichun AU - Wang Y AD - Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Mei, Jie AU - Mei J AD - Department of Gynecology and Obstetrics, Wuxi Maternal and Child Health Hospital, The Affiliated Hospital to Nanjing Medical University, Wuxi, China. AD - Wuxi Clinical Medical College, Nanjing Medical University, Wuxi, China. FAU - Nie, Sipei AU - Nie S AD - Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Zhang, Yan AU - Zhang Y AD - Department of Gynecology and Obstetrics, Wuxi Maternal and Child Health Hospital, The Affiliated Hospital to Nanjing Medical University, Wuxi, China. LA - eng PT - Journal Article DEP - 20210723 PL - Switzerland TA - Front Cell Dev Biol JT - Frontiers in cell and developmental biology JID - 101630250 PMC - PMC8343236 OTO - NOTNLM OT - chemotherapy OT - endometrial carcinoma OT - immunotherapy OT - prognosis OT - tumor immune microenvironment COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/08/10 06:00 MHDA- 2021/08/10 06:01 PMCR- 2021/01/01 CRDT- 2021/08/09 06:41 PHST- 2021/02/24 00:00 [received] PHST- 2021/07/01 00:00 [accepted] PHST- 2021/08/09 06:41 [entrez] PHST- 2021/08/10 06:00 [pubmed] PHST- 2021/08/10 06:01 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fcell.2021.671736 [doi] PST - epublish SO - Front Cell Dev Biol. 2021 Jul 23;9:671736. doi: 10.3389/fcell.2021.671736. eCollection 2021.