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Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
A Study to Evaluate the Potential Role and Clinical Application Value of Long Noncoding RNA CASC Family Members in
Chao Liang1, Jun Wang1, Xinyu Liu2
1Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Abstract:
Background: Long noncoding RNA (lncRNA) CASC, crucial in colorectal cancer (CRC) progression, remains largely unexplored despite its potential. Methods: 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. Results: 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. Conclusion: 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.
