Identification of theranostic factors for patients developing metastasis after surgery for early-stage lung adenocarcinoma.

Autor:	Cheng WC; Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taiwan.; Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan.; Research Center for Cancer Biology, China Medical University Hospital, Taichung 404, Taiwan., Chang CY; Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan., Lo CC; Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan., Hsieh CY; Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan., Kuo TT; Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan., Tseng GC; Department of Anatomic Pathology, Nantou Hospital of the Ministry of Health and Welfare, Nantou 540, Taiwan., Wong SC; Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan., Chiang SF; Lab of Precision Medicine, Feng-Yuan Hospital, Ministry of Health and Welfare, Taichung 420, Taiwan., Huang KC; Translation Research Core, China Medical University Hospital, Taichung 404, Taiwan.; Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung 404, Taiwan., Lai LC; Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan., Lu TP; Department of Public Health, National Taiwan University, Taipei 100, Taiwan., Chao KSC; Cancer Center, China Medical University Hospital, Taichung 404, Taiwan.; School of Medicine, China Medical University, Taichung 404, Taiwan., Sher YP; Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan.; Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan.; Chinese Medicine Research Center, China Medical University, Taichung 404, Taiwan.; Research Center for Chinese Herbal Medicine, China Medical University, Taichung 404, Taiwan.
Jazyk:	angličtina
Zdroj:	Theranostics [Theranostics] 2021 Jan 26; Vol. 11 (8), pp. 3661-3675. Date of Electronic Publication: 2021 Jan 26 (Print Publication: 2021).
DOI:	10.7150/thno.53176
Abstrakt:	Rationale: Lung adenocarcinoma (LUAD) is an aggressive disease with high propensity of metastasis. Among patients with early-stage disease, more than 30% of them may relapse or develop metastasis. There is an unmet medical need to stratify patients with early-stage LUAD according to their risk of relapse/metastasis to guide preventive or therapeutic approaches. In this study, we identified 4 genes that can serve both therapeutic and diagnostic (theranostic) purposes. Methods: Three independent datasets (GEO, TCGA, and KMPlotter) were used to evaluate gene expression profile of patients with LUAD by unbiased screening approach. Upon significant genes uncovered, functional enrichment analysis was carried out. The predictive power of their expression on patient prognosis were evaluated. Once confirmed their theranostic roles by integrated bioinformatics, we further conducted in vitro and in vivo validation. Results: We found that four genes ( ADAM9 , MTHFD2 , RRM2, and SLC2A1) were associated with poor patient outcomes with an increased hazard ratio in LUAD. Knockdown of them, both separately and simultaneously, suppressed lung cancer cell proliferation and migration ability in vitro and prolonged survival time in metastatic tumor mouse models. Moreover, these four biomarkers were found to be overexpressed in tumor tissues from LUAD patients, and the total immunohistochemical staining scores correlated with poor prognosis. Conclusions: These results suggest that these four identified genes could be theranostic biomarkers for stratifying high-risk patients who develop relapse/metastasis in early-stage LUAD. Developing therapeutic approaches for the four biomarkers may benefit early-stage LUAD patients after surgery. Competing Interests: Competing Interests: The authors have declared that no competing interest exists. (© The author(s).)
Databáze:	MEDLINE
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