Identification of AK3L1 as a New Lung Cancer Tumor Progression‐associated Gene by Comparative Genomic and Proteomic Analysis

Abstract

Lung cancer is the leading cause of cancer deaths worldwide. The challenge of finding a cure for lung cancer is to offer insights into metastasis in their developing stages. In this study we wished to identify new lung cancer metastasis‐associated biomarkers by utilizing global cDNA microarray and 2D‐gel proteomic analysis in metastatic lung cancer cells. We further validated our candidate pool by lung cancer patient tissue array analysis. In addition, we produced lentiviruses with specific shRNA to test their effects on lung cancer cell migration and invasion potentials. Our results showed 16 genes up‐regulated and 29 genes down‐regulated in invasive CL1–5 cell line. Of the 16 genes upregulated in CL1–5, we identified and characterized a novel gene AK3L1 as a lung cancer metastasis‐associated gene. Overexpression of AK3L1 protein was found primarily in late stage lung cancer and in patient with distal metastasis and significantly associated with dismal outcome by immunohistochemistry analysis of archival paraffin samples. Furthermore, knockdown of AK3L1 gene expression was found to sufficiently inhibit tumor invasion/migration potentials in CL1–5 and other lung cancer cell lines in vitro and in vivo. The possible mechanisms of AK3L1 with tumor involvement and metastasis were further explored. In conclusions, we have identified a new lung cancer progression gene AK3L1 by global RNA microarray and proteomic analysis, we have also validated this gene functions and mechanisms in vitro and in vivo. AK3L1 may be of value as a new biomarker in predicting the clinical outcome of lung cancers.