Quantitative proteomics reveals that distant recurrence-associated protein R-Ras and Transgelin predict post-surgical survival in patients with Stage III colorectal cancer

Oncotarget. 2016 Jul 12;7(28):43868-43893. doi: 10.18632/oncotarget.9701.

Abstract

Surgical resection supplemented with adjuvant chemotherapy is the current preferred treatment for Stage III colorectal cancer (CRC). However, as many as 48% of patients who undergo curative resection eventually suffer from incurable distant recurrence. To investigate the molecular mechanisms involved in Stage III CRC post-surgical distant recurrence, we identified a total of 146 differentially expressed proteins (DEPs) associated with distant recurrence in Stage III CRC using TMT-based quantitative mass spectrometry. Among these DEPs, the altered expressions of R-Ras and Transgelin were then validated in 192 individual specimens using immunohistochemistry (IHC). Furthermore, Kaplan-Meier analysis revealed that the levels of R-Ras and Transgelin were significantly associated with 5-year overall survival (OS) and disease-free survival (DFS), and multivariate Cox-regression analyses revealed that R-Ras and Transgelin were independent prognostic factors for OS and DFS, respectively. In conclusion, this study identified potential biochemical players involved in distant recurrence and indicates that R-Ras and Transgelin are potential post-surgical prognostic biomarkers for Stage III CRC. This proteomics data have been submitted to Proteome Xchange under accession number PXD002903.

Keywords: R-Ras and Transgelin; Stage III colorectal cancer; post-surgical recurrence; prognostic biomarker; quantitative proteomics.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Microfilament Proteins / analysis
  • Microfilament Proteins / biosynthesis*
  • Middle Aged
  • Muscle Proteins / analysis
  • Muscle Proteins / biosynthesis*
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology*
  • Prognosis
  • Proportional Hazards Models
  • Proteomics / methods
  • ras Proteins / analysis
  • ras Proteins / biosynthesis*

Substances

  • Biomarkers, Tumor
  • Microfilament Proteins
  • Muscle Proteins
  • transgelin
  • RRAS protein, human
  • ras Proteins