CLK2 Expression Is Associated with the Progression of Colorectal Cancer and Is a Prognostic Biomarker

Abstract

Background: CLK2 is a splicing regulator and expressed ubiquitously in various malignancies. The study is aimed at exploring the potential roles of CLK2 in the development of colorectal cancer (CRC).

Methods: Real-time PCR and analyses of The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) database were utilized to evaluate the CLK2 gene transcription level and protein level of colorectal cancer (CRC) tissue. The chi-squared and logistic regression tests were used to evaluate the relationship between CLK2 and clinicopathologic features. Kaplan-Meier survival curve and Cox regression analysis were performed to explore the prognostic significance of CLK2. The association between CLK2 expression and immune landscapes was explored by CIBERSORT and ESTIMATE. Furthermore, GSEA (Gene Set Enrichment Analysis) and alternative splicing (AS) analyses were performed to investigate the relationship between CLK2 expression and downstream signaling pathway.

Results: The CLK2 expression was upregulated in CRC in both transcript and protein level. The elevated expression of CLK2 was correlated with local invasion and poor prognosis. Furthermore, CLK2 induced tumor cell adhesion and thereby promotes local invasion of CRC. The CLK2 expression significantly inhibited plasma cells and eosinophil infiltration and showed no relationship with immune and stromal scores of CRC samples. CLK2 might involve in Notch signaling pathway by regulating the AS of CTBP1.

Conclusions: CLK2 might be a potential prognostic biomarker and therapeutic target for colorectal cancer.