The role of cell surface proteins gene expression in diagnosis, prognosis, and drug resistance of colorectal cancer: In silico analysis and validation

Exp Mol Pathol. 2021 Dec:123:104688. doi: 10.1016/j.yexmp.2021.104688. Epub 2021 Sep 27.

Abstract

Cell surface proteins (CSPs) are an important type of protein in different essential cell functions. This study aimed to distinguish overexpressed CSPs in colorectal cancer to investigate their biomarker, prognosis, and drug resistance potential. Raw data of three datasets including 1187 samples was downloaded then normalization and differential expression were performed. By the combination of the cancer genome atlas (TCGA) clinical data, survival analysis was carried out. Information of all CSPs was collected from cell surface protein atlas. The role of each candidate gene expression was investigated in drug resistance by CCEL and GDSC data from PharmacoGX. CRC samples including 30 tumor samples and adjacent normal were used to confirm data by RT-qPCR. Outcomes showed that 66 CSPs overexpressed in three datasets, and 146 CSPs expression associated with poor prognosis features in TCGA data that TIMP1 and QSOX2 can associate with poor patient survival independently. High-risk patients illustrated more fatality than low-risk patients based on the risk score calculated by the expression level of these genes. Receiver operating characteristic curve analysis showed that 39 CSPs as perfect biomarkers for diagnosis in CRC. Furthermore, QSOX2 and TIMP1 expression levels increased in tumor samples compared to adjacent normal samples. The Drug resistance analysis demonstrated ADAM12 and COL1A2 up-regulation among 66 overexpressed CSPs caused resistance to Venetoclax and Cyclophosphamide with a high estimate, respectively. Many CSPs are deregulated in CRC, and can be valuable candidates as biomarkers for diagnosis, prognosis, and drug resistance.

Keywords: Biomarker; Drug selection; Gene expression; Survival rate; Tumor sample.

MeSH terms

  • ADAM12 Protein / genetics*
  • Biomarkers, Tumor / genetics
  • Bridged Bicyclo Compounds, Heterocyclic / adverse effects
  • Bridged Bicyclo Compounds, Heterocyclic / therapeutic use
  • Collagen Type I / genetics*
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Computer Simulation
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use
  • Disease-Free Survival
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Oxidoreductases Acting on Sulfur Group Donors / genetics*
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use
  • Tissue Inhibitor of Metalloproteinase-1 / genetics*

Substances

  • Biomarkers, Tumor
  • Bridged Bicyclo Compounds, Heterocyclic
  • COL1A2 protein, human
  • Collagen Type I
  • Membrane Proteins
  • Sulfonamides
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Cyclophosphamide
  • Oxidoreductases Acting on Sulfur Group Donors
  • QSOX2 protein, human
  • ADAM12 Protein
  • ADAM12 protein, human
  • venetoclax