J Cancer 2021; 12(14):4148-4171. doi:10.7150/jca.58076

Research Paper

An integrative microenvironment approach for laryngeal carcinoma: the role of immune/methylation/autophagy signatures on disease clinical prognosis and single-cell genotypes

Xueran Kang1#, Yisheng Chen2#, Bin Yi1, Xiaojun Yan1, Chenyan Jiang1, Bin Chen1, Lixing Lu1, Yuxing Sun1, Runjie Shi1✉

1. Department of Otolaryngology-Head and Neck Surgery, Shanghai ninth people's Hospital, Shanghai Jiao Tong University School of Medicine; Ear Institute, Shanghai JiaoTong University School of Medicine; Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases, Shanghai, China.
2. Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
#These authors contributed equally to this work.

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Citation:
Kang X, Chen Y, Yi B, Yan X, Jiang C, Chen B, Lu L, Sun Y, Shi R. An integrative microenvironment approach for laryngeal carcinoma: the role of immune/methylation/autophagy signatures on disease clinical prognosis and single-cell genotypes. J Cancer 2021; 12(14):4148-4171. doi:10.7150/jca.58076. Available from https://www.jcancer.org/v12p4148.htm

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Abstract

The effects of methylation/autophagy-related genes (MARGs) and immune infiltration in the tumor microenvironment on the prognosis of laryngeal cancer were comprehensively explored in this study. Survival analysis screened out 126 MARGs and 10 immune cells potentially associated with the prognosis of laryngeal carcinoma. Cox and lasso regression analyses were then used to select 8 MARGs (CAPN10, DAPK2, MBTPS2, ST13, CFLAR, FADD, PEX14 and TSC2) and 2 immune cells (Eosinophil and Mast cell) to obtain the prognostic risk scoring system (pRS). The pRS was used to establish a risk prediction model for the prognosis of laryngeal cancer. The predictive ability of the prediction model was evaluated by GEO datasets and our clinical samples. Further analysis revealed that pRS is highly associated with single nucleotide polymorphism (SNP), copy number variation (CNV), immune checkpoint blockade (ICB) therapy and tumor microenvironment. Moreover, the screened pRS-related ceRNA network and circ_0002951/miR-548k/HAS2 pathway provide potential therapeutic targets and biomarkers of laryngocarcinoma. Based on the clustering results of pRS-related genes, single cells were then genotyped and revealed by integrated scRNA-seq in laryngeal cancer samples. Fibroblasts were found enriched in high risk cell clusters at the scRNA-seq level. Fibroblast-related ligand-receptor interactions were then exposed and a neural network-based deep learning model based on these pRS-related hub gene signatures was also established with a high accuracy in cell type prediction. In conclusion, the combination of single-cell and transcriptome laryngeal carcinoma landscape analyses can investigate the link between the tumor microenvironmental and prognostic characteristics.

Keywords: methylation, autophagy, immune infiltration, laryngocarcinoma, immunotherapy, ceRNA network