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Abstract
Surgery is the only curative treatment for early-stage non-small cell lung cancer (NSCLC) patients. However, approximately one-third of these patients develop recurrence, which remains the main cause of mortality in the postsurgical treatment of NSCLC. Many molecular markers have been proposed to predict recurrence of early-stage disease, but no marker has demonstrated sufficient reliability for clinical application. In the present study, the novel protein EF-hand domain-containing protein D2 (EFHD2) was identified as expressed in highly metastatic tumor cells. EFHD2 increased the formation of protrusive invadopodia structures and cell migration and invasion abilities and promoted the epithelial-to-mesenchymal transition (EMT) character of lung adenocarcinoma cells. We demonstrated that the mechanism of EFHD2 in enhancing EMT occurs partly through inhibition of caveolin-1 (CAV1) for cancer progression. The expression of EFHD2 was significantly correlated with postsurgical recurrence of patients with stage I lung adenocarcinoma in the Kaplan-Meier-plotter cancer database search and our retrospective cohort study (HR, 6.14; 95% CI, 2.40–15.74; P < 0.001). Multivariate Cox regression analysis revealed that EFHD2 expression was an independent clinical predictor for this disease. We conclude that EFHD2 expression is associated with increased metastasis and EMT and could serve as an independent marker to predict postsurgical recurrence of patients with stage I lung adenocarcinoma.
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1 Department of Superintendent Office, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medical Laboratory Science and Biotechnology, Yuanpei University, Hsinchu, Taiwan
2 Research Center for Tumor Medical Science, China Medical University, Taichung, Taiwan; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
3 School of Chinese Medicine, China Medical University, Taichung, Taiwan; Genetics Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
4 Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan
5 Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan
6 Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
7 Genomics Research Center, Academia Sinica, Taipei, Taiwan; Institute of Biochemistry & Molecular Biology, National Yang-Ming University, Taipei, Taiwan; Department of Chemistry, National Taiwan University, Taipei, Taiwan; Institute of Atomic & Molecular Sciences, Academia Sinica, Taipei, Taiwan