CLK2 upregulation and outcomes for males with colorectal adenocarcinoma.

Abstract

159 Background: Colorectal adenocarcinoma (COAD) is a common cancer in gastrointestinal tract. CDC-like kinase (CLK) family, containing four characterized isoforms (CLK1-4), have been reported for their roles in precursor-mRNA splicing. However, studies on their roles in COAD are limited. Thus, this study was performed to explore the roles of CLK family members in COAD. Methods: RNA-sequencing FPKM data and corresponding clinical information of 41 normal tissues and 480 tumor tissues of COAD were obtained from The Cancer Genome Atlas (TCGA). Then expression differences of CLK family between the normal tissues and COAD cancer tissues were compared with Wilcoxon rank-sum test via ‘limma’ package. Overall survival (OS) of upregulated CLK family members was analyzed by Kaplan–Meier (K–M) method via ‘survminer’ package. Subgroup analyses of different genders were also conducted. The best discriminate cut-off point between the high and low expression groups was assessed by the receiver operating characteristic (ROC) curve and area under the curve (AUC) values for upregulated CLK family members via ‘pROC’ package to assess their diagnostic values. Results: The expression of CLK1 and CLK2 were upregulated in tumors compared with normal tissues (p < 0.001), while CLK3 were downregulated in tumor tissues (p = 0.02) and no statically significant difference was found regarding CLK4 (p = 0.25). Higher expression of CLK1 was not associated with a change of OS (HR: 1.24, 95%CI: 0.84-1.83, p = 0.279), while higher expression of CLK2 is associated with worse OS (HR: 2.03, 95%CI: 1.34-3.06, p = 0.001). Subgroup analysis found that higher expression of CLK2 was associated with worse OS (HR: 2.28, 95%CI 1.27-4.08, p = 0.006) in males, but not in females (HR: 1.72, 95%CI 0.95-3.10, P = 0.072). Further analysis of ROC curve shown that AUC of CLK1 and CLK2 were 0.748 (0.687-0.809) and 0.884 (0.840-0.928), respectively. Conclusions: CLK1 and CLK2 are upregulated in COAD tumor samples, and higher expression of CLK2 in male COAD patients is associated worse OS. This demonstrated the potential therapeutic value of CLK2 in male patients with COAD. ROC curve indicated the potential diagnostic value of CLK1 and CLK2.