关键词: 结直肠癌, 循环肿瘤细胞, 生物标志物

Abstract:

Background and purpose: Colorectal cancer (CRC) is globally recognized as one of the most prevalent malignant tumors. Advanced CRC is marked by a relatively poor prognosis for patients, signifying an urgent need to identify novel potential biomarkers for CRC. A particular focus has been given to circulating tumor cells (CTC), which are cells that have detached from the primary tumor mass and subsequently entered the circulatory system. These cells can be detected within the blood and are currently considered significant potential biomarkers for CRC. This study aimed to investigate if FCGBP and BIGH3 in CRC could be potential markers for colorectal cancer. Methods: This study obtained 3 CRC datasets (GSE74369, GSE117606, and GSE164191) with CTC from the GEO database. Bioinformatics analysis was conducted to screen differentially expressed genes between CTC and normal samples. One dataset that includes clinical information was used for WGCNA analysis, and two key gene modules were identified, containing 1 148 genes in total. Then, functional enrichment analysis was carried out for these genes in the modules. Venn diagrams, PPI network construction analysis, and candidate gene screening were employed. Finally, survival analysis was performed using TCGA and GTEx data in the GEPIAS database, and key genes associated with CRC were identified. The expression of BIGH3 gene was validated in colorectal cancer tissues by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR), and its association with colorectal cancer was verified through clonogenic, scratch, and transwell assays in HCT116 and SW620 cell lines. Results: Through the analysis of CRC datasets from GEO, we screened a total of 2 214 differential genes. With the help of WGCNA analysis and PPI network construction, 4 CTC-related genes associated with CRC were identified. Survival analysis from the GEPIA database revealed that FCGBP and BIGH3 are associated with overall survival and disease-free survival. Further experiments indicated that BIGH3 gene is overexpressed in 30 matched colorectal cancer samples. The downregulation of BIGH3 expression could slow down cell proliferation and migration rates, as well as decrease invasiveness in HCT116 and SW620 cell lines. In contrast, upregulation of BIGH3 expression could increase its invasiveness or accelerate migration rate. Conclusion: FCGBP and BIGH3 are positively correlated with TNM staging, indicating their pivotal roles in CRC progression. They bear good prognostic value and may serve as potential biological markers for CRC clinically, and could provide potential therapeutic targets. Moreover, our experimental data revealed the crucial role of BIGH3 in colorectal cancer, suggesting it may influence the biological behavior of this disease.

Key words: Colorectal cancer, Circulating tumor cells, Biomarkers