Characterization of a cleavage stimulation factor, 3' pre-RNA, subunit 2, 64 kDa (CSTF2) as a therapeutic target for lung cancer

Abstract

Purpose: This study aims to discover novel biomarkers and therapeutic targets for lung cancers.

Experimental design: We screened for genes showing elevated expression in the majority of lung cancers by genome-wide gene expression profile analysis of 120 lung cancers obtained by cDNA microarray representing 27,648 genes or expressed sequence tags. In this process, we detected a gene encoding cleavage stimulation factor, 3' pre-RNA, subunit 2, 64 kDa (CSTF2) as a candidate. Immunohistochemical staining using tissue microarray consisting of 327 lung cancers was applied to examine the expression of CSTF2 protein and its prognostic value. A role of CSTF2 in cancer cell growth was examined by siRNA experiments.

Results: Northern blot and immunohistochemical analyses detected the expression of CSTF2 only in testis among 16 normal tissues. Immunohistochemical analysis using tissue microarray showed an association of strong CSTF2 expression with poor prognosis of patients with non-small cell lung cancer (P = 0.0079), and multivariate analysis showed that CSTF2 positivity is an independent prognostic factor. In addition, suppression of CSTF2 expression by siRNAs suppressed lung cancer cell growth, whereas exogenous expression of CSTF2 promoted growth and invasion of mammalian cells.

Conclusions: CSTF2 is likely to play an important role in lung carcinogenesis and be a prognostic biomarker in the clinic.