CLCA4 and MS4A12 as the significant gene biomarkers of primary colorectal cancer

Abstract

Background: Primary colorectal cancer (PCRC) is a common digestive tract cancer in the elderly. However, the treatment effect of PCRC is still limited, and the long-term survival rate is low. Therefore, further exploring the pathogenesis of PCRC, and searching for specific molecular targets for diagnosis are development trends of precise medical treatment, which have important clinical significance. Methods: The public data was downloaded from Gene Expression Omnibus (GEO) database. Verification for repeatability of intra-group data was performed by Pearson’s correlation test and principal component analysis. Differentially expressed genes (DEGs) between normal and PCRC were identified, and the Protein-protein interaction (PPI) network was constructed. Significant module and hub genes were found in the PPI network. A total of 192 PCRC patients were recruited between 2010 and 2019 from the Fourth Hospital of Hebei Medical University. RT-PCR was used to measure the relative expression of CLCA4 and MS4A12. Furthermore, the study explored the effect of expression of CLCA4 and MS4A12 for overall survival. Results: A total of 53 DEGs were identified between PCRC and normal colorectal tissues. Ten hub genes concerned to PCRC were screened, namely CLCA4, GUCA2A, GCG, SST, MS4A12, PLP1, CHGA, PYY, VIP, and GUCA2B. The PCRC patients with low expression of CLCA4 and MS4A12 has a worse overall survival than high expression of CLCA4 and MS4A12 (P<0.05). Conclusion: The research of DEGs in PCRC (53 DEGs, 10 hub genes, especially CLCA4 and MS4A12) and related signaling pathways is conducive to the differential analysis of the molecular mechanism of PCRC.

Association Between Obesity and Incident Colorectal Cancer: An Analysis Based on Colorectal Cancer Database in the Cancer Genome Atlas

“…Current studies supported that MS4A12 is a colon-speci c gene regulated by intestinal differentiation transcription factor CDX2 [12,13] and in adenomatous polyp, MS4A12 transcription is downregulated while CDX2 gene and protein expression upregulated [13,14]. Survival analysis of primary colorectal cancer patients showed that patients with low expression of MS4A12 had a worse survival rate than those with high expression of MS4A12, suggesting that MS4A12 was involved in the occurrence and development of primary colorectal cancer and could inhibit the progression of cancer, which may be a potential target for diagnosis and treatment [15]. What's more, MS4A12 can predict prognosis in early stage colon cancer patient and mainly relate to malignancy of non-metastasis tumor while the prognosis value of metastasis colon tumor is low [13].…”

Expression of the CLCA4 Gene in Esophageal Carcinoma and Its Impact on the Biologic Function of Esophageal Carcinoma Cells

“…CLCA4 overexpression was found to significantly decline the cell proliferation and metastasis ability in head and neck squamous cell carcinoma cells [ 24 ]. Furthermore, CLCA4 might be a target gene for primary colorectal cancer [ 25 ]. In addition, the tumor xenograft experiment was performed to detect the function of CLCA4 on the tumorigenicity in vivo.…”

Análisis transcriptómico del remodelado de la homeostasis del calcio intracelular en cáncer de colon

“…No obstante, en los últimos años se ha visto que, al contrario de lo que estos resultados indican, la expresión de MS4A12 está reducida en el cáncer de colon y, además, que a menor expresión pero es su pronóstico (J. Han et al (2020), J. W. Han et al (2021)). Es más, la disminución de su expresión inhibe la diferenciación de las células de cáncer de colon, característico de las células cancerígenas (L. He, Deng, and others (2017)).…”

“…Es más, el peor pronóstico y la menor supervivencia de los pacientes parece estar directamente relacionado con la menor expresión de MS4A12 (J. Han et al (2020)).…”

“…Otro gen sumamente importante como marcador del pronóstico del CCR es MS4A12, proteína implicada no solo en SOCE, sino también en la proliferación, diferenciación y regulación del ciclo celular, pues se ha relacionado su disminución con un peor pronóstico del CCR (L. He, Deng, and others (2017), J. Han et al (2020), J. W. Han et al (2021)). De hecho, su disminución ha mostrado una pérdida de la diferenciación de las células cancerígenas en el CCR, lo que es característico de las células cancerígenas y que, además, esta falta de diferenciación da cuenta de la proliferación de estas células.…”