Effect of cancer-associated fibroblasts on prognosis and immune infiltration in head and neck squamous cell carcinoma
Received date: 01 Nov 2023
Revised date: 17 Feb 2024
Accepted date: 12 Mar 2024
Copyright
Cancer-associated fibroblasts (CAFs) are the center of cross-communication between various cells in the tumor stroma. However, how CAFs-associated genes play an important role in Head and neck squamous cell carcinoma (HNSCC) prognosis has not been reported. Transcriptome data were downloaded from TCGA and GEO databases. Devtools, DPIC, xCell, MCPcounter, and Estimate packages were used to calculate CAFs scores and immune infiltration. Prognosis and weighted gene coexpression network analysis (WGCNA) analysis were performed between high or low risk populations based on CAF scores. Hub genes were identified, intersected, and enriched between TCGA and GEO databases. CAFs related genes were used to construct a prognostic model and the tumor immune dysfunction and exclusion database was used to evaluate the immune infiltration. Drug sensitivity, difference analysis and the HPA database were used to identify sensitive drugs and verify their expression. TCGA and GEO data suggested that CAFs scores had a role in HNSCC prognosis prediction. Based on CAFs scores, WGCNA and core gene enrichment analysis were performed to construct a CAFs-related prognostic model. The prognostic model composed of a total of 12 CAFs genes could predict the prognosis well and was validated in the validation dataset, demonstrating its applicability to external data. According to the model, although there was no statistical difference in immune escape between the high and low risk groups, the proportion of patients who responded to immunotherapy was different. Drug sensitivity also differed between the two groups. This study suggests that CAFs associated genetic signatures may help to optimize risk stratification and provide new insights into individualized cancer treatment.
Yuan-yuan Xu , Huanfeng Zhu , Dan Zong , Luxi Qian , Yi Cai , Nan Xiang . Effect of cancer-associated fibroblasts on prognosis and immune infiltration in head and neck squamous cell carcinoma[J]. Precision Medical Sciences, 2024 , 13(2) : 118 -129 . DOI: 10.1002/prm2.12129
1 |
Takahashi H, Sakakura K, Kawabata-Iwakawa R, et al. Immunosuppressive activity of cancer-associated fibroblasts in head and neck squamous cell carcinoma. Cancer Immunol Immunother. 2015;64:1407-1417.
|
2 |
Mao X, Xu J, Wang W, et al. Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives. Mol Cancer. 2021;20:131.
|
3 |
Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008;9:559.
|
4 |
Yu G, Wang LG, Han Y, He QY. clusterProfiler: an R package for comparing biological themes among gene clusters. Omics. 2012;16:284-287.
|
5 |
Ko YC, Lai TY, Hsu SC, et al. Index of cancer-associated fibroblasts is superior to the epithelial-mesenchymal transition score in prognosis prediction. Cancers (Basel). 2020;12(7):1718.
|
6 |
Sahai E, Astsaturov I, Cukierman E, et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat Rev Cancer. 2020;20:174-186.
|
7 |
Costa A, Kieffer Y, Scholer-Dahirel A, et al. Fibroblast heterogeneity and immunosuppressive environment in human breast cancer. Cancer Cell. 2018;33:463-479.e10.
|
8 |
Navab R, Strumpf D, Bandarchi B, et al. Prognostic gene-expression signature of carcinoma-associated fibroblasts in non-small cell lung cancer. Proc Natl Acad Sci U S A. 2011;108:7160-7165.
|
9 |
Du Y, Jiang X, Wang B, et al. The cancer-associated fibroblasts related gene CALD1 is a prognostic biomarker and correlated with immune infiltration in bladder cancer. Cancer Cell Int. 2021;21:283.
|
10 |
Chen Z, Zhuo S, He G, et al. Prognosis and immunotherapy significances of a cancer-associated fibroblasts-related gene signature in gliomas. Front Cell Dev Biol. 2021;9:721897.
|
11 |
Li M, Wang L, Zhan Y, et al. Membrane Metalloendopeptidase (MME) suppresses metastasis of esophageal squamous cell carcinoma (ESCC) by inhibiting FAK-RhoA signaling Axis. Am J Pathol. 2019;189:1462-1472.
|
12 |
Yao S, Zhao L, Chen S, et al. Cervical cancer immune infiltration microenvironment identification, construction of immune scores, assisting patient prognosis and immunotherapy. Front Immunol. 2023;14:1135657.
|
13 |
Li S, Zhang N, Liu S, et al. ITGA5 is a novel oncogenic biomarker and correlates with tumor immune microenvironment in gliomas. Front Oncol. 2022;12:844144.
|
14 |
Zhu H, Wang G, Zhu H, Xu A. ITGA5 is a prognostic biomarker and correlated with immune infiltration in gastrointestinal tumors. BMC Cancer. 2021;21:269.
|
15 |
Feng C, Jin X, Han Y, et al. Expression and prognostic analyses of ITGA3, ITGA5, and ITGA6 in head and neck squamous cell carcinoma. Med Sci Monit. 2020;26:e926800.
|
16 |
Wu DC, Zhang MF, Su SG, et al. HEY2, a target of miR-137, indicates poor outcomes and promotes cell proliferation and migration in hepatocellular carcinoma. Oncotarget. 2016;7:38052-38063.
|
17 |
Feng T, Sun L, Qi W, et al. Prognostic significance of Tspan9 in gastric cancer. Mol Clin Oncol. 2016;5:231-236.
|
18 |
Guo H, Liu R, Wu J, et al. SRPX2 promotes cancer cell proliferation and migration of papillary thyroid cancer. Clin Exp Med. 2023;23:4825-4834.
|
19 |
Su G, Wang W, Xu L, Li G. Progress of EGFL6 in angiogenesis and tumor development. Int J Clin Exp Pathol. 2022;15:436-443.
|
20 |
Song EL, Hou YP, Yu SP, et al. EFEMP1 expression promotes angiogenesis and accelerates the growth of cervical cancer in vivo. Gynecol Oncol. 2011;121:174-180.
|
21 |
Ji FH, Qiu XG. THBS1, a fatty acid-related metabolic gene, can promote the development of laryngeal cancer. Sci Rep. 2022;12:18809.
|
22 |
Fan S, Wang Y, Sheng N, et al. Low expression of ENC1 predicts a favorable prognosis in patients with ovarian cancer. J Cell Biochem. 2019;120:861-871.
|
23 |
Liu T, Han C, Wang S, et al. Cancer-associated fibroblasts: an emerging target of anti-cancer immunotherapy. J Hematol Oncol. 2019;12:86.
|
24 |
Itoh G, Takagane K, Fukushi Y, et al. Cancer-associated fibroblasts educate normal fibroblasts to facilitate cancer cell spreading and T-cell suppression. Mol Oncol. 2022;16:166-187.
|
25 |
Erez N, Truitt M, Olson P, Arron ST, Hanahan D. Cancer-associated fibroblasts are activated in incipient neoplasia to orchestrate tumor-promoting inflammation in an NF-kappaB-dependent manner. Cancer Cell. 2010;17:135-147.
|
/
〈 | 〉 |