Four Prognosis-Associated lncRNAs Serve as Biomarkers in Ovarian Cancer.

Jianfeng Zheng,Guomin Xu,Huizhi Zhang,Zhifen Zhang,Benben Cao,Jialu Guo,Jinyi Tong

doi:10.3389/fgene.2021.672674

Abstract

Long non-coding RNAs (lncRNAs) play crucial roles in ovarian cancer (OC) development. However, prognosis-associated lncRNAs (PALs) for OC have not been completely elucidated. Our study aimed to identify the PAL signature of OC. A total of 663 differentially expressed lncRNAs were identified in the databases. According to the weighted gene coexpression analysis, the highly correlated genes were clustered into seven modules related to the clinical phenotype of OC. A total of 25 lncRNAs that were significantly related to overall survival were screened based on univariate Cox regression analysis. The prognostic risk model constructed contained seven PALs based on the parameter λmin, which could stratify OC patients into two risk groups. The results showed that the risk groups had different overall survival rates in both The Cancer Genome Atlas (TCGA) and two verified Gene Expression Omnibus (GEO) databases. Univariate and multivariate Cox regression analyses confirmed that the risk model was an independent risk factor for OC. Gene enrichment analysis revealed that the identified genes were involved in some pathways of malignancy. The competitive endogenous RNA (ceRNA) network included five PALs, of which four were selected for cell function assays. The four PALs were downregulated in 33 collected OC tissues and 3 OC cell lines relative to the control. They were shown to regulate the proliferative, migratory, and invasive potential of OC cells via Cell Counting Kit-8 (CCK-8) and transwell assays. Our study fills the gaps of the four PALs in OC, which are worthy of further study.

Highlights

Ovarian cancer (OC) is a gynecological malignancy with the highest morbidity and mortality rates worldwide (Stewart et al, 2019)
RNAs with expression levels >0 in 33% of the samples were identified as messenger RNAs or long non-coding RNA (lncRNA) based on annotation information from the GENCODE database (Harrow et al, 2012)
A total of 1,467 upregulated messenger RNAs (mRNAs) and 1,431 downregulated mRNAs were extracted (Figure 2A), and 307 lncRNAs expressed at high levels and 356 lncRNAs expressed at low levels were obtained (Figure 2B)

Summary

Introduction

Ovarian cancer (OC) is a gynecological malignancy with the highest morbidity and mortality rates worldwide (Stewart et al, 2019). The prognosis of patients in early cancer stages is better, most patients are already in the late stages of OC during the first diagnosis (Kaldawy et al, 2016; Eisenhauer, 2017). There is a need to identify novel biomarkers for predicting tumorigenesis and clinical diagnosis in earlier stages and to develop new therapeutic strategies and targets for OC. Previous studies have found that lncRNAs could serve as strong prognostic biomarkers and play an important role in. SNHG9 was shown to serve as an anticancer biomarker by regulating miR-214-5p (Chen et al, 2021). LINC01969 was confirmed to be a cancer-promoting biological marker via the miR-144-5p/LARP1 axis (Chen et al, 2020)

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