High P4HA1 expression is an independent prognostic factor for poor overall survival and recurrent-free survival in head and neck squamous cell carcinoma.

Qun Li,Chongchang Zhou,Zhenhua Wu,Huigao Liu,Hongxia Deng,Zhisen Shen,Yi Shen

doi:10.1002/jcla.23107

Abstract

BackgroundProlyl 4‐hydroxylase subunit alpha 1 (P4HA1) plays a critical role in modulating the extracellular matrix and promoting tumor progression in various cancers. However, the association between P4HA1 and head and neck squamous cell carcinomas (HNSCC) has not been thoroughly elucidated to date.Methods P4HA1 mRNA and protein expression in cancer and normal tissues were analyzed using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus, and Human Protein Atlas databases. Quantitative PCR was applied to determine P4HA1 mRNA expression levels in 162 paired HNSCC and adjacent normal tissues. The cBioPortal for Cancer Genomics was utilized to explore P4HA1 genetic alterations in HNSCC. Then, KEGG analysis of P4HA1 co‐expressed genes in HNSCC was conducted using ClueGo in Cytoscape.Results P4HA1 mRNA and protein levels were significantly increased in HNSCC tissues compared with normal tissues. High P4HA1 expression in HNSCC tissues was significantly associated with tumor category, lymphatic metastasis and pathological stage. The area under summary receiver operating characteristic curve of TCGA and validation cohort was 0.887 and 0.883, respectively. Moreover, elevated P4HA1 expression was associated with unfavorable OS (HR: 1.728, P = .001) and RFS (HR: 2.025, P = .002) in HNSCC patients.ConclusionsThis integrated analysis provides strong evidence that increasing P4HA1 expression is significantly associated with the carcinogenesis of HNSCC. Additionally, high P4HA1 expression serves as both diagnostic biomarker and independent prognostic factor for poor OS and RFS in HNSCC patients.

Highlights

Head and neck cancers represent the sixth most common cancer worldwide
By comparing Prolyl 4-hydroxylase subunit alpha 1 (P4HA1) mRNA expression using the RNA-Seq data of 520 head and neck squamous cell carcinomas (HNSCC) tissues and normal tissues in The Cancer Genome Atlas (TCGA), we revealed that HNSCC tissues exhibited significantly elevated P4HA1 mRNA expression compared with normal tissues (P = 1.64E23; Figure 1A,B), consistent with our findings using Gene Expression Omnibus (GEO) data (P = 6.16E-04; Figure 1C)
In univariate Cox proportional hazards analysis, the results showed that elderly (hazard ratio (HR): 1.318, 95% confidence interval (CI): 1.003-1.731, P = .047), female (HR: 1.349, 95% CI: 1.014-1.796, P = .04), advanced stages (HR: 1.754, 95% CI: 1.2032.558, P = .004), lymphatic metastasis (HR: 1.86, 95% CI: 1.3432.576, P = 1.86E-04), and elevated P4HA1 expression (HR: 1.775, 95% CI: 1.358-2.321, P = 2.68E-05) were associated with unfavorable overall survival (OS)

Summary

| INTRODUCTION

The vast majority (greater than 90%) are head and neck squamous cell carcinomas (HNSCC), such that the term head and neck cancer refers to cancer arising from the epithelium lining the of the upper aerodigestive tract (lip, oral cavity, pharynx, and larynx) and exhibiting microscopic evidence of squamous differentiation.[1] According to the latest report of the International Agency for Research on Cancer, approximately one million new HNSCC patients were estimated to be clinically diagnosed in 2018 with greater than 542 943 deaths worldwide.[2] The risk for developing HNSCC is associated with several traditional etiological factors, including cigarette smoking and alcohol abuse.[3] Increasing evidence demonstrates that infection with a high-risk human papillomavirus (HPV) strain is associated with HNSCC and is an important favorable prognostic factor, especially for oral cavity and oropharynx cancer.[4,5] the recent diagnostic and therapeutic strategies have yielded some significant improvements, the 5-year survival rate for HNSCC patients over the last decade remained at approximately 50%.6. P4HA1 plays an essential role in enhancing invasion and metastasis and is significantly associated with decreased patient survival.[17] until now, the association between P4HA1 and HNSCC as well as its clinical value was not clearly delineated. We investigated the enrichment of P4HA1 co-expressed genes in KEGG pathways to explore its underlying mechanism in HNSCC

| MATERIALS AND METHODS

| DISCUSSION

Findings

| CONCLUSIONS