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.

Keywords: Y-linked genes; gender difference; head and neck squamous cell carcinoma (HNSCC); immune response; minor histocompatibility antigen (MHC); overall survival.