Y‐Chromosome‐Linked Genes Are Associated With Sex‐Related Head‐Neck Squamous Cell Carcinoma Survival

Abstract Objective To define novel gene biomarkers for prognosis of head and neck squamous cell carcinoma (HNSCC) patients' survival. Study Design Retrospective study. Setting The Cancer Genome Atlas (TCGA) HNSCC RNA‐Seq dataset. Methods Coexpressed gene clusters were extracted from TCGA RNA‐seq data using our previously published method (EPIG). Kaplan‐Meier estimator was then used for overall survival‐relevant analysis, with patients partitioned into 3 groups based on gene expression levels: female, male_low, and male_high. Results Male had better overall survival than female and male with higher expression level of Y‐chromosome‐linked (Y‐linked) genes had significantly better survival than those with lower expression levels. In addition, male with a higher expression level of Y‐linked genes showed even better survival when they have a higher level of coexpressed cluster of genes related to B or T cell immune response. Other clinical conditions related to immune responses also consistently showed favorable effects on the Y‐linked genes for survival estimation. Male patients with higher expression level of Y‐linked genes also have significantly higher tumor/normal tissue (T/N) ratio of those genes and higher level of several immune responses related clinical measurements (eg, lymphocyte and TCR related). Male patients with lower expression level of Y‐linked genes benefited from radiation‐only treatment. Conclusions The favorable role of a cluster of coexpressed Y‐linked genes in HNSCC patients' survival is potentially associated with elevated level of immune responses. These Y‐linked genes could serve as useful prognostic biomarkers for HNSCC patients' survival estimation and treatment.