Integrated analysis of HPV-mediated immune alterations in cervical cancer.

Abstract:

OBJECTIVE:Human papillomavirus (HPV) infection is the primary cause of cervical cancer. HPV-mediated immune alterations are known to play crucial roles in determining viral persistence and host cell transformation. We sought to thoroughly understand HPV-directed immune alterations in cervical cancer by exploring publically available datasets. METHODS:130 HPV positive and 7 HPV negative cervical cancer cases from The Cancer Genome Atlas were compared for differences in gene expression levels and functional enrichment. Analyses for copy number variation (CNV) and genetic mutation were conducted for differentially expressed immune genes. Kaplan-Meier analysis was performed to assess survival and relapse differences across cases with or without alterations of the identified immune signature genes. RESULTS:Genes up-regulated in HPV positive cervical cancer were enriched for various gene ontology terms of immune processes (P=1.05E-14~1.00E-05). Integrated analysis of the differentially expressed immune genes identified 9 genes that displayed either CNV, genetic mutation and/or gene expression changes in at least 10% of the cases of HPV positive cervical cancer. Genomic amplification may cause elevated levels of these genes in some HPV positive cases. Finally, patients with alterations in at least one of the nine signature genes overall had earlier relapse compared to those without any alterations. The altered expression of either TFRC or MMP13 may indicate poor survival for a subset of cervical cancer patients (P=1.07E-07). CONCLUSIONS:We identified a novel immune gene signature for HPV positive cervical cancer that is potentially associated with early relapse of cervical cancer.

journal_name

Gynecol Oncol

journal_title

Gynecologic oncology

authors

Chen L,Luan S,Xia B,Liu Y,Gao Y,Yu H,Mu Q,Zhang P,Zhang W,Zhang S,Wei G,Yang M,Li K

doi

10.1016/j.ygyno.2018.01.031

subject

Has Abstract

pub_date

2018-05-01 00:00:00

pages

248-255

issue

2

eissn

0090-8258

issn

1095-6859

pii

S0090-8258(18)30070-2

journal_volume

149

pub_type

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