Integrated genomic analysis of recurrence-associated small non-coding RNAs in oesophageal cancer.

Autor:	Jang HJ; Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.; Division of Cancer Medicine, Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.; Department of Molecular Oncology, The Graduate School of Medicine, Seoul National University, Seoul, Republic of Korea., Lee HS; Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.; Division of Cancer Medicine, Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.; Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA.; Lung Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea., Burt BM; Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA., Lee GK; Lung Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea., Yoon KA; Lung Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.; College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea., Park YY; Division of Cancer Medicine, Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Sohn BH; Division of Cancer Medicine, Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Kim SB; Division of Cancer Medicine, Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Kim MS; Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea., Lee JM; Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea., Joo J; Biometric Research Branch, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea., Kim SC; Department of Biomedical Informatics, Center for Genome Science, National Institute of Health, KCDC, Choongchung-Buk-do, Republic of Korea., Yun JS; Lung and Esophageal Cancer Clinic, Department of Thoracic and Cardiovascular Surgery, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea., Na KJ; Lung and Esophageal Cancer Clinic, Department of Thoracic and Cardiovascular Surgery, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea., Choi YL; Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea., Park JL; Department of Functional Genomics, University of Science and Technology, Medical Genomics Research Center, KRIBB, Daejeon, Republic of Korea., Kim SY; Department of Functional Genomics, University of Science and Technology, Medical Genomics Research Center, KRIBB, Daejeon, Republic of Korea., Lee YS; Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, Texas, USA., Han L; Division of Quantitative Sciences, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.; Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, Texas, USA., Liang H; Division of Quantitative Sciences, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Mak D; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Burks JK; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Zo JI; Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea., Sugarbaker DJ; Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA., Shim YM; Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea., Lee JS; Division of Cancer Medicine, Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Jazyk:	angličtina
Zdroj:	Gut [Gut] 2017 Feb; Vol. 66 (2), pp. 215-225. Date of Electronic Publication: 2016 Aug 09.
DOI:	10.1136/gutjnl-2015-311238
Abstrakt:	Objective: Oesophageal squamous cell carcinoma (ESCC) is a heterogeneous disease with variable outcomes that are challenging to predict. A better understanding of the biology of ESCC recurrence is needed to improve patient care. Our goal was to identify small non-coding RNAs (sncRNAs) that could predict the likelihood of recurrence after surgical resection and to uncover potential molecular mechanisms that dictate clinical heterogeneity. Design: We developed a robust prediction model for recurrence based on the analysis of the expression profile data of sncRNAs from 108 fresh frozen ESCC specimens as a discovery set and assessment of the associations between sncRNAs and recurrence-free survival (RFS). We also evaluated the mechanistic and therapeutic implications of sncRNA obtained through integrated analysis from multiple datasets. Results: We developed a risk assessment score (RAS) for recurrence with three sncRNAs (microRNA (miR)-223, miR-1269a and nc886) whose expression was significantly associated with RFS in the discovery cohort (n=108). RAS was validated in an independent cohort of 512 patients. In multivariable analysis, RAS was an independent predictor of recurrence (HR, 2.27; 95% CI, 1.26 to 4.09; p=0.007). This signature implies the expression of ΔNp63 and multiple alterations of driver genes like PIK3CA. We suggested therapeutic potentials of immune checkpoint inhibitors in low-risk patients, and Polo-like kinase inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and histone deacetylase inhibitors in high-risk patients. Conclusion: We developed an easy-to-use prognostic model with three sncRNAs as robust prognostic markers for postoperative recurrence of ESCC. We anticipate that such a stratified and systematic, tumour-specific biological approach will potentially contribute to significant improvement in ESCC treatment. (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)
Databáze:	MEDLINE
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