title: Integrated genomic analysis of recurrence-associated small non-coding RNAs in oesophageal cancer.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: 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.
authors: Hee-Jin
authors: HJ
authors: Jang
authors: 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.
authors: Hyun-Sung
authors: 0000-0001-8259-046X
authors: HS
authors: Lee
authors: Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA.
authors: Bryan M
authors: BM
authors: Burt
authors: Lung Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors: Geon Kook
authors: GK
authors: Lee
authors: 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.
authors: Kyong-Ah
authors: KA
authors: Yoon
authors: Division of Cancer Medicine, Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Yun-Yong
authors: YY
authors: Park
authors: Division of Cancer Medicine, Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Bo Hwa
authors: BH
authors: Sohn
authors: Division of Cancer Medicine, Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Sang Bae
authors: SB
authors: Kim
authors: Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors: Moon Soo
authors: MS
authors: Kim
authors: Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors: Jong Mog
authors: JM
authors: Lee
authors: Biometric Research Branch, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors: Jungnam
authors: J
authors: Joo
authors: Department of Biomedical Informatics, Center for Genome Science, National Institute of Health, KCDC, Choongchung-Buk-do, Republic of Korea.
authors: Sang Cheol
authors: SC
authors: Kim
authors: Lung and Esophageal Cancer Clinic, Department of Thoracic and Cardiovascular Surgery, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea.
authors: Ju Sik
authors: JS
authors: Yun
authors: Lung and Esophageal Cancer Clinic, Department of Thoracic and Cardiovascular Surgery, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea.
authors: Kook Joo
authors: KJ
authors: Na
authors: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Yoon-La
authors: YL
authors: Choi
authors: Department of Functional Genomics, University of Science and Technology, Medical Genomics Research Center, KRIBB, Daejeon, Republic of Korea.
authors: Jong-Lyul
authors: JL
authors: Park
authors: Department of Functional Genomics, University of Science and Technology, Medical Genomics Research Center, KRIBB, Daejeon, Republic of Korea.
authors: Seon-Young
authors: SY
authors: Kim
authors: Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, Texas, USA.
authors: Yong Sun
authors: YS
authors: Lee
authors: 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.
authors: Leng
authors: L
authors: Han
authors: Division of Quantitative Sciences, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Han
authors: H
authors: Liang
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Duncan
authors: D
authors: Mak
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Jared K
authors: JK
authors: Burks
authors: Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Jae Ill
authors: JI
authors: Zo
authors: Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA.
authors: David J
authors: DJ
authors: Sugarbaker
authors: Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Young Mog
authors: YM
authors: Shim
authors: Division of Cancer Medicine, Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: Ju-Seog
authors: JS
authors: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors; D045744:Cell Line, Tumor / Q000187:drug effects; D058534:Class I Phosphatidylinositol 3-Kinases; D018572:Disease-Free Survival; D004354:Drug Screening Assays, Antitumor; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D005260:Female; D023281:Genomics; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis* / Q000235:genetics; D008875:Middle Aged; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011237:Predictive Value of Tests; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors; D018570:Risk Assessment; D049490:Systems Biology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D014157:Transcription Factors / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000097869:Polo-Like Kinase 1
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D058534:Class I Phosphatidylinositol 3-Kinases; D056572:Histone Deacetylase Inhibitors; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000097869:Polo-Like Kinase 1; C000600169:MIRN1269 microRNA, human; C525067:MIR223, human; C559060:MIRN886 microRNA, human; C115051:TP63 protein, human; C484760:PIK3CA protein, human
keywords: CANCER IMMUNOBIOLOGY; GENE EXPRESSION; OESOPHAGEAL CANCER; RNA EXPRESSION; SURGICAL ONCOLOGY