Xu Haoya, Lu Miao, Liu Yuna, Ren Fang, Zhu Liancheng
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China.
Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China.
J Cancer. 2023 Sep 25;14(16):3151-3168. doi: 10.7150/jca.88485. eCollection 2023.
To identify the pyroptosis-related long non-coding RNAs (lncRNAs) in ovarian cancer and construct a prognostic signature based on them. 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. 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 , , , , , and , in which LINC01094 and KRT7-AS were found to be overexpressed in three ovarian cancer cell lines. 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.
鉴定卵巢癌中与细胞焦亡相关的长链非编码RNA(lncRNA),并基于这些lncRNA构建预后特征。利用来自TCGA的表达数据探索卵巢癌中差异表达的细胞焦亡相关lncRNA。通过LASSO和Cox回归分析建立风险特征并进行验证。使用ESTIMATE、CIBERSORT、TIMER、XCELL等数据库确定该特征与卵巢癌免疫微环境之间的关系。引入基因集富集分析来确定该特征可能参与的途径和功能。基于miRcode和starBase数据库,筛选与我们特征中的lncRNA相关的微小RNA以及正共表达的细胞焦亡相关基因,然后构建竞争性内源性RNA(ceRNA)网络。进行定量逆转录PCR以验证该ceRNA网络中两个lncRNA的表达水平。构建了一个由13个细胞焦亡相关lncRNA组成的预后特征(MYCNOS、AL161772.1、USP30-AS1、ZNF32-AS2、AC068733.3、AC012236.1、AC015802.5、KIAA1671-AS1、AC013403.2、MIR223HG、KRT7-AS、PTPRD-AS1和LINC01094)。高危组患者的预后明显比低危组差(P<0.0001)。免疫浸润分析发现,被鉴定为高危的患者巨噬细胞和肿瘤相关成纤维细胞的浸润更高。进一步的通路分析表明,该特征可能参与上皮-间质转化、细胞外基质受体相互作用和粘着斑。最后,发现LINC01094、KRT7-AS、MYCNOS、ZNF32-AS2、AC012236.1与 、 、 、 、 、 等细胞焦亡相关基因之间存在竞争性内源性抑制关系,其中发现LINC01094和KRT7-AS在三种卵巢癌细胞系中过表达。我们构建了一个与细胞焦亡相关的lncRNA特征,并将其与免疫微环境相关联。还构建了一个与细胞焦亡相关的ceRNA调控网络,这为卵巢癌中细胞焦亡的研究提供了新的见解。