A 4-gene signature predicts prognosis of uterine serous carcinoma

Hui Chen,Minfen Zhang,Hanzhen Xiong,Ping Qin,Qingping Jiang,Ruichao Chen,Lingjun Li

doi:10.1186/s12885-021-07834-4

Abstract

BackgroundUterine serous carcinoma (USC) is an aggressive type of endometrial cancer that accounts for up to 40% of endometrial cancer deaths, creating an urgent need for prognostic biomarkers.MethodsUSC RNA-Seq data and corresponding patients’ clinical records were obtained from The Cancer Genome Atlas and Genotype-Tissue Expression datasets. Univariate cox, Lasso, and Multivariate cox regression analyses were conducted to forge a prognostic signature. Multivariable and univariable cox regression analysis and ROC curve evaluated the prediction efficiency both in the training and testing sets.ResultsWe uncovered 1385 genes dysregulated in 110 cases of USC tissue relative to 113 cases of normal uterine tissue. Functional enrichment analysis of these genes revealed the involvement of various cancer-related pathways in USC. A novel 4-gene signature (KRT23, CXCL1, SOX9 and ABCA10) of USC prognosis was finally forged by serial regression analyses. Overall patient survival (OS) and recurrence-free survival (RFS) were significantly lower in the high-risk group relative to the low-risk group in both the training and testing sets. The area under the ROC curve of the 4-gene signature was highest among clinicopathological features in predicting OS and RFS. The 4-gene signature was found to be an independent prognostic indicator in USC and was a superior predictor of OS in early stage of USC.ConclusionsOur findings highlight the potential of the 4-gene signature as a guide for personalized USC treatment.

Highlights

Uterine serous carcinoma (USC) is an aggressive type of endometrial cancer that accounts for up to 40% of endometrial cancer deaths, creating an urgent need for prognostic biomarkers
The cancer genome atlas (TCGA)-USC patient characteristics A dataset of 110 UCS samples and 35 adjacent normal uterus tissue samples was downloaded from TCGA
Identification of dysregulated genes in USC and functional enrichment analysis To ensure that our analysis compared equivalent numbers of USC and non-USC cases, we downloaded a dataset of normal uterus tissue samples from Genotype-tissue expression (GTEx) (n = 78), which along with the 35 in the TCGA dataset brought the total number of normal uterine cases to 113

Summary

Introduction

Uterine serous carcinoma (USC) is an aggressive type of endometrial cancer that accounts for up to 40% of endometrial cancer deaths, creating an urgent need for prognostic biomarkers. Endometrial cancer is the 2nd most common gynecologic malignancy worldwide [1]. In China it ranks the 2nd most common female cancer of the genital tract [2]. Uterine serous carcinoma (USC/uterine serous papillary carcinoma) was first described by Hendrickson in 1982 [3]. It represents a type of endometrial cancer whose clinicopathological and molecular features deviate from those of endometrioid carcinoma (EEC). Myometrium invasion, percentage (mean ± SD) 50.1 ± 7.3 Stage, no(%) Early (I + II) 53 (48.2)

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