Identification of a pyroptosis-related long non-coding RNA Signature for prognosis and its related ceRNA regulatory network of ovarian cancer

Haoya Xu; Miao Lu; Yuna Liu; Fang Ren; Liancheng Zhu

doi:10.7150/jca.88485

Identification of a pyroptosis-related long non-coding RNA Signature for prognosis and its related ceRNA regulatory network of ovarian cancer

J Cancer. 2023 Sep 25;14(16):3151-3168. doi: 10.7150/jca.88485. eCollection 2023.

Authors

Haoya Xu^{1

2

3}, Miao Lu¹, Yuna Liu¹, Fang Ren¹, Liancheng Zhu¹

Affiliations

¹ Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China.
² Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China.
³ Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China.

Abstract

Aim: To identify the pyroptosis-related long non-coding RNAs (lncRNAs) in ovarian cancer and construct a prognostic signature based on them. Methods: Expression data from TCGA was used to explore differentially expressed pyroptosis-related lncRNAs in ovarian cancer. A risk signature was established by LASSO and cox regression analysis and then validated. Databases such as ESTIMATE, CIBERSORT, TIMER, XCELL were used to identify the relation between this signature and the immune microenvironment of ovarian cancer. Gene Set Enrichment Analysis was introduced to identify the pathways and functions that the signature may participate in. Based on miRcode and starBase databases, microRNAs related to the lncRNAs in our signature and the positively co-expressed pyroptosis- related genes were screened and a competing endogenous RNA (ceRNA) network was then constructed. Quantitative reverse transcription PCR was conducted to validate the expression levels of two lncRNAs in this ceRNA network. Results: A 13 pyroptosis-related lncRNA prognostic signature (MYCNOS, AL161772.1, USP30-AS1, ZNF32-AS2, AC068733.3, AC012236.1, AC015802.5, KIAA1671-AS1, AC013403.2, MIR223HG, KRT7-AS, PTPRD-AS1 and LINC01094) was constructed. Patients in high-risk group had a significantly worse prognosis than that of low-risk (P<0.0001). Immune infiltration analysis found that patients identified as high-risk had a higher infiltration of macrophages and tumor-associated fibroblasts. Further pathway analysis revealed that the signature may be involved in epithelial mesenchymal transition, extracellular matrix receptor interaction, and focal adhesion. Finally, a competitive endogenous inhibition relationship was discovered between LINC01094, KRT7-AS, MYCNOS, ZNF32-AS2, AC012236.1 and pyroptosis- related genes such as IRF1, NOD1, GSDMC, NLRP1, PLCG1, GSDME and GZMB, in which LINC01094 and KRT7-AS were found to be overexpressed in three ovarian cancer cell lines. Conclusion: We constructed a pyroptosis-related lncRNA signature and correlate it to the immune microenvironment. A ceRNA regulatory network related to pyroptosis was also constructed, which provides novel insights useful for the study of pyroptosis in ovarian cancer.

Keywords: ceRNA regulatory network; immune microenvironment; lncRNA; ovarian cancer; pyroptosis-related genes.