PMID- 36938461 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230321 IS - 2405-8440 (Print) IS - 2405-8440 (Electronic) IS - 2405-8440 (Linking) VI - 9 IP - 3 DP - 2023 Mar TI - Identification and verification of eight cancer-associated fibroblasts related genes as a prognostic signature for head and neck squamous cell carcinoma. PG - e14003 LID - 10.1016/j.heliyon.2023.e14003 [doi] LID - e14003 AB - Cancer-associated fibroblasts (CAFs) can exert their immunosuppressive effects by secreting various effectors that are involved in the regulation of tumor-infiltrating immune cells as well as other immune components in the tumor immune microenvironment (TIME), thereby promoting tumorigenesis, progression, metastasis, and drug resistance. Although a large number of studies suggest that CAFs play a key regulatory role in the development of head and neck squamous cell carcinoma (HNSCC), there are limited studies on the relevance of CAFs to the prognosis of HNSCC. In this study, we identified a prognostic signature containing eight CAF-related genes for HNSCC by univariate Cox analysis, lasso regression, stepwise regression, and multivariate Cox analysis. Our validation in primary cultures of CAFs from human HNSCC and four human HNSCC cell lines confirmed that these eight genes are indeed characteristic markers of CAFs. Immune cell infiltration differences analysis between high-risk and low-risk groups according to the eight CAF-related genes signature hinted at CAFs regulatory roles in the TIME, further revealing its potential role on prognosis. The signature of the eight CAF-related genes was validated in different independent validation cohorts and all showed that it was a valid marker for prognosis. The significantly higher overall survival (OS) in the low-risk group compared to the high-risk group was confirmed by Kaplan-Meier (K-M) analysis, suggesting that the signature of CAF-related genes can be used as a non-invasive predictive tool for HNSCC prognosis. The low-risk group had significantly higher levels of tumor-killing immune cell infiltration, as confirmed by CIBERSORT analysis, such as CD8(+) T cells, follicular helper T cells, and Dendritic cells (DCs) in the low-risk group. In contrast, the level of infiltration of pro-tumor cells such as M0 macrophages and activated Mast cells (MCs) was lower. It is crucial to delve into the complex mechanisms between CAFs and immune cells to find potential regulatory targets and may provide new evidence for subsequently targeted immunotherapy. These results suggest that the signature of the eight CAF-related genes is a powerful indicator for the assessment of the TIME of HNSCC. It may provide a new and reliable potential indicator for clinicians to predict the prognosis of HNSCC, which may be used to guide treatment and clinical decision-making in HNSCC patients. Meanwhile, CAF-related genes are expected to become tumor biomarkers and effective targets for HNSCC. CI - (c) 2023 The Authors. FAU - Dong, Lei AU - Dong L AD - Department of Otorhinolaryngology Head and Neck Surgery, Yantai Yuhuangding Hospital, Shandong University, China. AD - Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases. FAU - Sun, Qi AU - Sun Q AD - Department of Otorhinolaryngology Head and Neck Surgery, Yantai Yuhuangding Hospital, Shandong University, China. AD - Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases. FAU - Song, Fei AU - Song F AD - Department of Otorhinolaryngology Head and Neck Surgery, Yantai Yuhuangding Hospital, Shandong University, China. AD - Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases. FAU - Song, Xiaoyu AU - Song X AD - Department of Otorhinolaryngology Head and Neck Surgery, Yantai Yuhuangding Hospital, Shandong University, China. AD - Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases. FAU - Lu, Congxian AU - Lu C AD - Department of Otorhinolaryngology Head and Neck Surgery, Yantai Yuhuangding Hospital, Shandong University, China. AD - Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases. FAU - Li, Yumei AU - Li Y AD - Department of Otorhinolaryngology Head and Neck Surgery, Yantai Yuhuangding Hospital, Shandong University, China. AD - Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases. FAU - Song, Xicheng AU - Song X AD - Department of Otorhinolaryngology Head and Neck Surgery, Yantai Yuhuangding Hospital, Shandong University, China. AD - Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases. LA - eng PT - Journal Article DEP - 20230228 PL - England TA - Heliyon JT - Heliyon JID - 101672560 PMC - PMC10018481 OTO - NOTNLM OT - CAFs, Cancer-associated fibroblasts OT - CSCs, cancer stem cells OT - Cancer-associated fibroblasts OT - DCs, Dendritic cells OT - EMT, epithelial mesenchymal transition OT - GEO, Gene Expression Omnibus OT - GEPIA, Gene Expression Profiling Interactive Analysis OT - GO, Gene Ontology OT - GSEA, Gene Set Enrichment Analysis OT - HNSCC, head and neck squamous cell carcinoma OT - HR, Hazard Ratio OT - Head and neck squamous cell carcinoma OT - Immune cell infiltration OT - K-M, Kaplan-Meier OT - KEGG, Kyoto Encyclopedia of Genes and Genomes OT - MCs, Mast cells OT - NFs, normal fibroblasts OT - OS, overall survival OT - OSCC, oral squamous cell carcinomas OT - Prognostic signature OT - ROC, receiver operating characteristic OT - TAMs, tumor-associated macrophages OT - TCGA, The Cancer Genome Atlas OT - TIME, tumor immune microenvironment OT - TME, tumor microenvironment COIS- The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/03/21 06:00 MHDA- 2023/03/21 06:01 PMCR- 2023/02/28 CRDT- 2023/03/20 04:18 PHST- 2022/09/02 00:00 [received] PHST- 2023/02/16 00:00 [revised] PHST- 2023/02/17 00:00 [accepted] PHST- 2023/03/20 04:18 [entrez] PHST- 2023/03/21 06:00 [pubmed] PHST- 2023/03/21 06:01 [medline] PHST- 2023/02/28 00:00 [pmc-release] AID - S2405-8440(23)01210-0 [pii] AID - e14003 [pii] AID - 10.1016/j.heliyon.2023.e14003 [doi] PST - epublish SO - Heliyon. 2023 Feb 28;9(3):e14003. doi: 10.1016/j.heliyon.2023.e14003. eCollection 2023 Mar.