SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are prognosis-related in colorectal cancer

World J Gastroenterol. 2011 Apr 21;17(15):2028-36. doi: 10.3748/wjg.v17.i15.2028.

Abstract

Aim: To investigate the expression of markers that are correlated with the prognosis of colorectal cancer (CRC) patients.

Methods: One hundred and fifty-six CRC patients were followed up for more than 3 years after radical surgery. Immunohistochemical (IHC) analysis was performed to detect the expression of 14 pathway-related markers (p53, APC, p21ras, E-cadherin, endothelin-B receptor, Shp2, ADCY-2, SPARCL1, neuroligin1, hsp27, mmp-9, MAPK, MSH2 and rho) in specimens from these patients. Bioinformatics analysis involving a Support Vector Machine (SVM) was used to determine the best prognostic model from combinations of these markers.

Results: Seven markers (SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK) were significantly related to the prognosis and clinical pathological features of the CRC patients (P < 0.05). Prognostic models were established through SVM from combinations of these 7 markers and proved able to differentiate patients with dissimilar survival, especially in stage II/III patients. According to the best prognostic model, the p53/SPARCL1 model, patients having high p53 and low SPARCL1 expression had about 50% lower 3-year survival than others (P < 0.001).

Conclusion: SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are potential prognostic markers in CRC. A p53/SPARCL1 bioinformatics model may be used as a supplement to tumor-nodes-metastasis staging.

Keywords: Bioinformatics; Colorectal cancer; Prognosis; SPARCL1; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / metabolism*
  • Biomarkers, Tumor / metabolism
  • Cadherins / metabolism*
  • Calcium-Binding Proteins / metabolism*
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Extracellular Matrix Proteins / metabolism*
  • Humans
  • Kaplan-Meier Estimate
  • Mitogen-Activated Protein Kinases / metabolism*
  • MutS Homolog 2 Protein / metabolism*
  • Neoplasm Staging
  • Prognosis
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism*
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Biomarkers, Tumor
  • Cadherins
  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • SPARCL1 protein, human
  • Tumor Suppressor Protein p53
  • Mitogen-Activated Protein Kinases
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • MSH2 protein, human
  • MutS Homolog 2 Protein
  • Adenylyl Cyclases
  • adenylyl cyclase 2