Four transcription profile-based models identify novel prognostic signatures in oesophageal cancer.

Journal: Journal of cellular and molecular medicine
Published Date:

Abstract

Oesophageal cancer (ESCA) is a clinically challenging disease with poor prognosis and health-related quality of life. Here, we investigated the transcriptome of ESCA to identify high risk-related signatures. A total of 159 ESCA patients of The Cancer Genome Atlas (TCGA) were sorted by three phases. In the discovery phase, differentially expressed transcripts were filtered; in the training phase, two adjusted Cox regressions and two machine leaning models were used to construct and estimate signatures; and in the validation phase, prognostic signatures were validated in the testing dataset and the independent external cohort. We constructed two signatures from three types of RNA markers by Akaike information criterion (AIC) and least absolute shrinkage and selection operator (LASSO) Cox regressions, respectively, and all candidate markers were further estimated by Random Forest (RFS) and Support Vector Machine (SVM) algorithms. Both signatures had good predictive performances in the independent external oesophageal squamous cell carcinoma (ESCC) cohort and performed better than common clinicopathological indicators in the TCGA dataset. Machine learning algorithms predicted prognosis with high specificities and measured the importance of markers to verify the risk weightings. Furthermore, the cell function and immunohistochemical (IHC) staining assays identified that the common risky marker FABP3 is a novel oncogene in ESCA.

Authors

  • Tongyan Liu
    Department of Thoracic Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
  • Panqi Fang
    Department of Thoracic Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
  • Chencheng Han
    Department of Thoracic Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
  • Zhifei Ma
    Department of Thoracic Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
  • Weizhang Xu
    Department of Thoracic Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
  • Wenjia Xia
    Department of Thoracic Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
  • Jingwen Hu
    Department of Thoracic Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
  • Youtao Xu
    Department of Thoracic Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
  • Lin Xu
    Key Laboratory of Grain and Oil Processing and Food Safety of Sichuan Province, College of Food and Bioengineering, Xihua University Chengdu 610039 China xingyage1@163.com.
  • Rong Yin
    West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China. rong.yin@scupi.cn.
  • Siwei Wang
    Department of Thoracic Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
  • Qin Zhang
    Department of Burn, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.