Integrative genomic analyses on interferon-lambdas and their roles in cancer prediction

Abstract

Interferon (IFN)-lambdas, including IFN-lambda1, IFN-lambda2, and IFN-lambda3, are a newly described group of cytokines distantly related to the type I IFNs and IL-10 family members. Besides the antiviral activity, IFN-lambdas were reported to inhibit various tumor growths in vitro and in vivo. Herein, we identified IFN-lambda genes from the genome sequences of the human, chimpanzee, macaque, orangutan, mouse, rat and dog, and found that the locations and copy of a specific IFN-lambda varied in different genomes, not just the copy of IFN-lambdas. We found human IFN-lambdas were expressed in fetal retina, fetal brain and T cells by ESTs search. Moreover, IFN-lambdas were also found to express in bladder cancer, blood cancer, breast cancer, glioma, head and neck cancer and lung cancer tissues. Three tumor-related transcriptional factors (steroidogenic factor-1, Wilms tumor 1 and P53) binding sites were identified within the 1.0-kb regions upstream of the transcriptional start site of human IFN-lambdas. Meta-analysis of the prognostic value of IFN-lambda genes in various cancers showed that the expression of IFN-lambdas are indeed related to the cancer prognosis in certain types of cancer. It can be predicted that IFN-lambdas take part in the cancer development by the regulation of expression of IFN-lambdas related to the SF-1, P53 and WT-1.