High stromal nicotinamide N-methyltransferase (NNMT) indicates poor prognosis in colorectal cancer

Cancer Med. 2020 Mar;9(6):2030-2038. doi: 10.1002/cam4.2890. Epub 2020 Jan 27.

Abstract

Purpose: Nicotinamide n-methyltransferase (NNMT) has good biochemical activity and epigenetic regulation, and has been reported as a major metabolic regulator of cancer. The goal of this study was to investigate the significance of stromal NNMT expression in colorectal cancer (CRC).

Patients and methods: Stromal expression of NNMT in primary CRC, metastasis CRC, and their non-cancerous tissues from 1088 CRC patients was examined by immunohistochemistry. The associations between stromal NNMT expression and survival outcomes in 967 patients with stage I-III CRC were further evaluated with Kaplan-Meier curve and Cox model analyses.

Results: NNMT expression was mainly sourced from stromal compartments and also elevated in CRC. Patients with high stromal NNMT (IHC-score ≥ 106) have a worse survival than those patients with low stromal NNMT. In multiple Cox analyses, high expression of stromal NNMT remained as an independent risk factor in CRC for disease-free survival with a hazard ratio (HR) of 1.415 (95% confidence interval [CI], 1.015-1.972) and disease-specific survival with a HR of 5.004 (95% CI, 2.301-10.883). In addition, high stromal NNMT expression in CRC also indicates the poor survival outcomes in patients with early stage CRC (stage I and II) and in patients who undergo chemotherapy.

Conclusion: NNMT is mainly located in CRC stromal compartment. High stromal NNMT expression predicts an unfavorable postoperative prognosis.

Keywords: NNMT; clinical significance; colorectal cancer; prognosis.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism*
  • Cancer-Associated Fibroblasts / metabolism*
  • Cell Line, Tumor
  • Chemotherapy, Adjuvant
  • Colon / cytology
  • Colon / pathology
  • Colon / surgery
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality*
  • Colorectal Neoplasms / therapy
  • Computational Biology
  • Datasets as Topic
  • Disease-Free Survival
  • Drug Resistance, Neoplasm / genetics
  • Epigenesis, Genetic
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Nicotinamide N-Methyltransferase / analysis
  • Nicotinamide N-Methyltransferase / metabolism*
  • Prognosis
  • Rectum / cytology
  • Rectum / pathology
  • Rectum / surgery
  • Tumor Microenvironment

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • NNMT protein, human
  • Nicotinamide N-Methyltransferase