Department of Oncology, Liuzhou People's Hospital, Liuzhou, 545001, Guangxi Zhuang Autonomous Region, China.
Sci Rep. 2022 Aug 30;12(1):14788. doi: 10.1038/s41598-022-19247-9.
Breast cancer (BC) is considered the second commonest human carcinoma and the most incident and mortal in the female population. Despite promising treatments for breast cancer, mortality rates of metastatic disease remain high. Gasdermin C (GSDMC) is an affiliate of the gasdermin (GSDM) family, which is involved in the process of pyroptosis. Pyroptosis is implicated in tumorigenesis, but the role of GSDMC in cancer cells is yet to be fully elucidated. In this study, we investigated the role and mechanism of GSDMC in breast cancer. We conducted a pan-cancer analysis of the expression and prognosis of GSDMC utilizing multidimensional data from The Cancer Genome Atlas (TCGA). We investigated GSDMC expression levels in 15 BC tissues and matched adjacent normal tissues by immunohistochemistry (IHC). Further verification was performed in the Gene Expression Omnibus (GEO) database. We discovered that elevated GSDMC expression was considerably linked to a worse prognosis in breast invasive carcinoma (BRCA). Next, we identified noncoding RNAs (ncRNAs) which contributing to higher expression of GSDMC by a series of expression, survival, and correlation analysis. We finally identified LINC00511/hsa-miR-573 axis to be the most promising ncRNA-associated pathways that account for GSDMC in BRCA. Furthermore, we demonstrated the significant correlations between GSDMC expression and immune infiltrates, immune checkpoints, and immune markers in BRCA. This study illustrated that ncRNAs-mediated upregulation of GSDMC linked to dismal prognosis and also exhibited a correlation with tumor immune cell infiltration in BRCA. It is anticipated to offer novel ideas for the link between pyroptosis and tumor immunotherapy.
乳腺癌(BC)被认为是第二常见的人类癌种,也是女性人群中发病率和死亡率最高的癌种。尽管针对乳腺癌有了有希望的治疗方法,但转移性疾病的死亡率仍然很高。Gasdermin C(GSDMC)是 gasdermin(GSDM)家族的一个分支,参与细胞焦亡过程。细胞焦亡与肿瘤发生有关,但 GSDMC 在癌细胞中的作用尚未完全阐明。在这项研究中,我们研究了 GSDMC 在乳腺癌中的作用和机制。我们利用癌症基因组图谱(TCGA)的多维数据对 GSDMC 的表达和预后进行了泛癌分析。我们通过免疫组织化学(IHC)检测了 15 例乳腺癌组织和配对的相邻正常组织中的 GSDMC 表达水平。进一步在基因表达综合数据库(GEO)数据库中进行了验证。我们发现,GSDMC 表达升高与乳腺癌浸润性癌(BRCA)的预后较差显著相关。接下来,我们通过一系列表达、生存和相关性分析,确定了导致 GSDMC 高表达的非编码 RNA(ncRNA)。我们最终确定 LINC00511/hsa-miR-573 轴是最有希望的与 GSDMC 相关的 ncRNA 通路,在 BRCA 中起作用。此外,我们还证明了 GSDMC 表达与 BRCA 中免疫浸润、免疫检查点和免疫标志物之间存在显著相关性。这项研究表明,ncRNA 介导的 GSDMC 上调与预后不良有关,并且与 BRCA 中的肿瘤免疫细胞浸润有关。它有望为细胞焦亡与肿瘤免疫治疗之间的联系提供新的思路。