High TKTL1 expression as a sign of poor prognosis in colorectal cancer with synchronous rather than metachronous liver metastases

Cancer Biol Ther. 2020 Sep 1;21(9):826-831. doi: 10.1080/15384047.2020.1803008. Epub 2020 Aug 14.

Abstract

Colorectal cancer (CRC) is the third most common cancer in the world. More than half of all affected patients develop liver metastases during the course of the disease, and over half experience recurrence despite radical primary surgery. Transketolase-like protein 1 (TKTL1) is a key enzyme in the glucose metabolism of cancer cells, and its expression in tumor tissue was previously shown to indicate a poor prognosis in colorectal cancer. In this study, we investigated the prognostic significance of TKTL1 in 111 patients with surgically resected colorectal liver metastases, with a minimum follow-up time of 10.3 years. TKTL1 expression was examined in tissue samples of both primary tumors and liver metastases, and compared to clinicopathological parameters, disease-free survival, and overall survival. We show that a high expression of TKTL1 in primary tumor tissue associated with poor disease-free survival in patients with synchronous liver metastases (P = .026, Kaplan-Meier log-rank test), but with better disease-free survival in patients with metachronous metastases, although not statistically significantly (P = .073). We found similar tendencies for TKTL1 expression in liver metastases. Thus, TKTL1 could serve as a candidate marker to identify patients who benefit from liver resection or who need more aggressive perioperative chemotherapy.

Keywords: TKTL1; colorectal cancer; immunohistochemistry; liver metastases; liver resection; prognosis; tumor markers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms / complications*
  • Female
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / secondary*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Prognosis
  • Transketolase / metabolism*

Substances

  • TKTL1 protein, human
  • Transketolase

Grants and funding

This work was supported by the State Research Funding (FI) [RP, CH, HI]; the Finnish Cancer Foundation [RP]; Suomen Onkologiayhdistys (FI) [RP]; Finska Läkaresällskapet [KA, CB, CH]; the K. Albin Johansson Foundation [KA, CB]; the Sigrid Jusélius Foundation [CH]; and Medicinska Understödsföreningen Liv och Hälsa [CH].