Predictive Potential of PD-L1, TYMS, and DCC Expressions in Treatment Outcome of Colorectal Carcinoma

Adv Exp Med Biol. 2020:1292:97-112. doi: 10.1007/5584_2020_521.

Abstract

Colorectal carcinoma (CRC) is a malignancy of epithelial origin in the large bowel. The elucidation of the biological functions of programmed cell death ligand-1 (PD-L1), thymidylate synthase (TYMS), and deleted in colorectal cancer (DCC) biomarkers including their roles in the pathophysiology of CRC - has led to their applications in diagnostic and chemo-pharmaceutics. We investigated whether PD-L1, TYMS, and DCC protein expression in CRC tumors are predictive biomarkers of treatment outcome for CRC patients. The expressions of PD-L1, TYMS, and DCC were evaluated by immunohistochemistry (IHC) in 91 paraffin-embedded samples from patients who underwent colectomy procedure in Hospital Serdang, Selangor, Malaysia. There was high expression of DCC in most cases: 84.6% (77/91). PD-L1 showed low expression in 93.4% (86/91) of cases and high expression in 6.6% (5/91) of cases. Low and high expressions of TYMS were detected in 53.8% (49/91) and 46.2% (42/91) of the CRC cases, respectively. There was a significant association between the TYMS expression and gender (P < 0.05); the expression of TYMS was observed at a high level in 76.2% of males and in 23.8% of females. The mean overall survival (OS) was 100 months for the CRC patients evaluated. The OS for patients with high expression of PD-L1 was 22 months. Patients with high expression of TYMS and DCC showed OS of 90 and 96 months, respectively. The results from this study suggest that PD-L1, TYMS, and DCC expression could be used as biomarkers to stratify CRC patients who could benefit from adjuvant therapy.

Keywords: Colorectal carcinoma; Deleted in colorectal cancer; Prognosis; Programmed cell death ligand-1; Thymidylate synthase.

MeSH terms

  • B7-H1 Antigen / biosynthesis
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / analysis*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism*
  • DCC Receptor / biosynthesis
  • DCC Receptor / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Thymidylate Synthase / biosynthesis
  • Thymidylate Synthase / metabolism*
  • Treatment Outcome

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • DCC Receptor
  • DCC protein, human
  • TYMS protein, human
  • Thymidylate Synthase