Decreased IFIT2 Expression In Human Non-Small-Cell Lung Cancer Tissues Is Associated With Cancer Progression And Poor Survival Of The Patients

Abstract

Wenya Su,1–4,* Wenlu Xiao,2–4,* Lujun Chen,2–4 Qi Zhou,2–4 Xiao Zheng,2–4 Jingfang Ju,5 Jingting Jiang,2–4 Zhigang Wang1 1Department of Respiration, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, People’s Republic of China; 2Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, People’s Republic of China; 3Jiangsu Engineering Research Center for Tumor Immunotherapy, Changzhou, Jiangsu 213003, People’s Republic of China; 4Institute of Cell Therapy, Soochow University, Changzhou, Jiangsu 213003, People’s Republic of China; 5Stony Brook University, Stony Brook, NY 11794, USA*These authors contributed equally to this workCorrespondence: Zhigang WangDepartment of Respiration, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu 213003, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected] JiangDepartment of Tumor Biological Treatment and Research Center for Cancer Immunotherapy Technology of Jiangsu Province, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu 213003, People’s Republic of ChinaTel [phone]Email [email protected]: IFIT2 (interferon-induced proteins with tetratricopeptide repeats 2), also known as ISG54, is an important interferon-stimulated gene family protein, which has been confirmed to play a crucial role in anti-cancer as well as anti-virus process. In the present study, we aimed to investigate the IFIT2 expression in human non-small-cell cancer (NSCLC) tissues and its clinical implications.Methods: The immunohistochemistry assay was used to identify the clinical significance and prognostic value of IFIT2 expression in NSCLC tissues. The depletion of IFIT2 was achieved using RNAi approach to assess the role of IFIT2 in the regulation of biological behaviors in human lung cancer cell lines.Results: Decreased IFIT2 expression was found in human NSCLC tissues (both in lung adenocarcinoma and lung squamous cell carcinoma) in contrast to the adjacent normal tissues (both P<0.0001, respectively). We did not find any significant correlations between the IFIT2 expression and patient’s clinicopathological features. The survival analysis showed that the overall survival (OS) of patients in IFIT2 low expression group was significantly poorer than that in IFIT2 high expression group (in lung adenocarcinoma: P=0.027; and in lung squamous cell carcinoma: P=0.029). The Cox model analysis also indicated that the distant metastasis (P=0.043) could be used as an independent prognostic factor for lung adenocarcinoma patients, and the lymph node metastasis (P=0.045) and IFIT2 low expression (P=0.020) could be used as independent prognostic factors for lung squamous cell carcinoma patients. Moreover, the depletion of IFIT2 in human lung cancer cell lines A549, H1975 and SK-MES-1 significantly increased the cellular abilities, such as viability, migration and invasion.Conclusion: Decreased IFIT2 was involved in the initiation and the progression of human NSCLC, and its underlying mechanisms still needs further investigation.Keywords: lung cancer, IFIT2, RNAi, prognosis  

Keywords

• Lung cancer
• IFIT2
• RNAi
• Prognosis