Liang Chao, Wang Jun, Liu Xinyu
Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Department of Geriatrics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Int J Genomics. 2025 Jul 24;2025:3881424. doi: 10.1155/ijog/3881424. eCollection 2025.
Long noncoding RNA (lncRNA) CASC, crucial in colorectal cancer (CRC) progression, remains largely unexplored despite its potential. The CRC data comes from The Cancer Genome Atlas (TCGA) database. The limma package was used to screen differentially expressed genes (DEGs), intersecting with CASC genes that yielded key hub lncRNAs. Next, the lncRNA-protein interaction network was developed applying Cytoscape software. The association between immune cell infiltration and lncRNAs was calculated using the ESTIMATE package, CIBERSORT package, and ssGSEA. Based on the survminer package to assess the correlation between hub gene expression levels and clinicopathologic features of CRC patients, cellular models were utilized to assess the mRNA expression levels and potential biological functions of the screened markers. We filtered 2326 DEGs that were notably enriched in pathways related to metastasis, cell growth, and EMT. This study found six hub lncRNAs (CASC15, CASC16, CASC8, CASC9, CASC19, and CASC18) showed a high diagnostic accuracy, with the area under the curve (AUC) values all exceeding 0.7. There were 44 proteins in the lncRNA-protein interaction network that interact with hub lncRNAs, among which both LIN28B and IGF2BP2 interact with six hub lncRNAs. Immune infiltration analysis indicated that the six hub lncRNAs were significantly correlated with the multiple types of immune cells. Pathological analysis demonstrated that the expression of CASC15 elevated with the progression of TNM staging. Cellular assays had revealed that all are significantly associated with CRC; particularly, CASC15 knockdown repressed the in vitro metastasis of CRC cells. We constructed and validated a robust signature of six lncRNA CASC for predicting survival of CRC patients and characterizing the immune infiltration landscape. These results reveal that the CASC gene family could be a therapeutic target for CRC patients.
长链非编码RNA（lncRNA）CASC在结直肠癌（CRC）进展中起关键作用，尽管其潜力巨大，但在很大程度上仍未得到充分研究。CRC数据来自癌症基因组图谱（TCGA）数据库。使用limma软件包筛选差异表达基因（DEG），并与产生关键枢纽lncRNA的CASC基因进行交叉分析。接下来，应用Cytoscape软件构建lncRNA-蛋白质相互作用网络。使用ESTIMATE软件包、CIBERSORT软件包和ssGSEA计算免疫细胞浸润与lncRNA之间的关联。基于survminer软件包评估枢纽基因表达水平与CRC患者临床病理特征之间的相关性，利用细胞模型评估筛选出的标志物的mRNA表达水平和潜在生物学功能。我们筛选出2326个DEG，这些基因显著富集于与转移、细胞生长和上皮-间质转化相关的通路。本研究发现六个枢纽lncRNA（CASC15、CASC16、CASC8、CASC9、CASC19和CASC18）具有较高的诊断准确性，曲线下面积（AUC）值均超过0.7。lncRNA-蛋白质相互作用网络中有44种蛋白质与枢纽lncRNA相互作用，其中LIN28B和IGF2BP2均与六个枢纽lncRNA相互作用。免疫浸润分析表明，这六个枢纽lncRNA与多种类型的免疫细胞显著相关。病理分析表明，CASC15的表达随TNM分期进展而升高。细胞实验表明所有这些都与CRC显著相关；特别是，敲低CASC15可抑制CRC细胞的体外转移。我们构建并验证了一个由六个lncRNA CASC组成的强大特征，用于预测CRC患者的生存情况并描绘免疫浸润格局。这些结果表明，CASC基因家族可能是CRC患者的治疗靶点。
