Hyperpolarization-activated cyclic nucleotide-gated gene signatures and poor clinical outcome of cancer patient

Abstract

Background: we investigated the mRNA expression of hyperpolarization-activated cyclic nucleotide-gated genes (HCN1-4) in multiple types and subtypes of cancers. Methods: We performed a meta-analysis of public microarray data from Oncomine and NextBio Research databases to discover the mRNA expression level of HCN1-4 in cancers. Survival analysis was also used to investigate the correlation between overexpression of HCN gene family with overall survival rate of cancer patients using Kaplan-Meier Plotter database and PROGgene V2 database. Results: HCN genes (HCN1-4) over-expression and under-expression in multiples types of cancers such as CNS and brain cancer, breast cancer, colorectal cancer, melanoma, and lymphoma were found. HCN1 was signi cantly correlated with low overall survival of breast cancer [hazard ratio (HR) =7.42, P=0.0019] and colorectal cancer (HR =1.66, P=0.0071) patients. The lower survival rates of lung cancer (HR =2.5, P= 0.0107), kidney cancer (HR =1.1, P=0.004) and gastric cancer (HR =1.33, P=0.0037) patients were significantly correlated with the expression of HCN2. HCN3 was signi cantly correlated to lower survival rates of breast cancer (HR =1.65, P=0.0016), and kidney cancer (HR =1.17, P=0.0049). HCN4 was highly correlated with the lower survival rates of breast cancer of gastric cancer (HR =1.25, P=0.022), lung cancer (HR =5.37, P=0.0433) and ovarian cancer (HR =13.58, P=0.0426). Conclusions: These data suggested that HCN genes (HCN1-4) are likely to be potential candidates for cancer diagnosis and prognosis.