Laboratory Animal Center, Dalian Medical University, Dalian, China.
Emergency Department, The Second Hospital of Dalian Medical University, Dalian, China.
PeerJ. 2024 Oct 29;12:e18374. doi: 10.7717/peerj.18374. eCollection 2024.
Pyroptosis is a form of regulated necrosis that occurs in many cell and tissue types and plays a critical role in tumor progression. The diagnostic value of pyroptosis-related genes (PRGs) in colon cancer has been widely investigated. In the present study, we explored the relationship between PRG expression and colon cancer.
We retrieved genomic and clinical data pertaining to The Cancer Genome Atlas-Colon Adenocarcinoma from the UCSC Xena database, along with the corresponding genome annotation information from the GENCODE data portal. Utilising these data and a list of 33 pyrogenic genes, we performed principal component analysis and unsupervised clustering analysis to assess the pyroptosis subtypes. We analysed the differential expression between these subtypes to obtain PRGs, ultimately selecting 10 PRGs. We conducted Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene set variation analysis, protein-protein interaction, and immune infiltration analyses of these PRGs. We validated the expression of TNNC1 immunohistochemistry (IHC) and real-time quantitative PCR.
After rigorous screening, excluding patients with incomplete survival data and unmatched transcriptomes, we refined our study cohort to 431 patients. We performed differential mRNA analysis and identified 445 PRGs, 10 of which were selected as hub genes. These genes were associated with various immune cell types. Specifically, expression was positively associated with immature dendritic cells and NK CD56 cells. IHC staining indicated higher TNNC1 expression levels in tumor samples. Notably, TNNC1 expression levels were high in all the colon cancer cell lines, particularly in SW480 cells.
In this study, we explored the characteristics of PRGs in colon cancer and identified novel biological targets for early individualised treatment and accurate diagnosis of colon cancer, thus contributing to the advancement of clinical oncology.
细胞焦亡是一种发生在多种细胞和组织类型中的程序性细胞死亡方式，在肿瘤进展中发挥着关键作用。细胞焦亡相关基因（PRGs）在结肠癌中的诊断价值已得到广泛研究。在本研究中，我们探讨了 PRG 表达与结肠癌之间的关系。
我们从 UCSC Xena 数据库中检索了与 The Cancer Genome Atlas-Colon Adenocarcinoma 相关的基因组和临床数据，以及从 GENCODE 数据门户获得相应的基因组注释信息。利用这些数据和 33 个致炎基因列表，我们进行了主成分分析和无监督聚类分析，以评估细胞焦亡亚型。我们分析了这些亚型之间的差异表达，获得了 PRGs，最终选择了 10 个 PRGs。我们对这些 PRGs 进行了基因本体论、京都基因与基因组百科全书、基因集变异分析、蛋白质-蛋白质相互作用和免疫浸润分析。我们验证了 TNNC1 免疫组织化学（IHC）和实时定量 PCR 的表达。
经过严格筛选，排除了生存数据不完整和转录组不匹配的患者后，我们将研究队列精减至 431 例患者。我们进行了差异 mRNA 分析，鉴定出 445 个 PRGs，其中 10 个被选为关键基因。这些基因与各种免疫细胞类型有关。具体来说，表达与未成熟树突状细胞和 NK CD56 细胞呈正相关。IHC 染色表明肿瘤样本中 TNNC1 的表达水平较高。值得注意的是，所有结肠癌细胞系中 TNNC1 的表达水平均较高，特别是在 SW480 细胞中。
在这项研究中，我们探讨了 PRGs 在结肠癌中的特征，并确定了新的生物学靶点，用于结肠癌的个体化早期治疗和准确诊断，从而推动临床肿瘤学的发展。
