Aberrant expression of WNK lysine deficient protein kinase 1 is associated with poor prognosis of colon adenocarcinoma

Ir J Med Sci. 2023 Feb;192(1):57-64. doi: 10.1007/s11845-021-02916-5. Epub 2022 Feb 9.

Abstract

Backgrounds: WNK1 (WNK lysine deficient protein kinase 1) is a kind of protein kinase and participates in angiogenesis, having a potent tumor promoting role. WNK1 is ubiquitously expressed, and its upregulated expression has been reported in several tumor types.

Aims: Here, we aimed to investigate the correlation between WNK1 expression and colon adenocarcinoma (COAD) progression.

Methods: In the current study, WNK1 expression was evaluated by immunohistochemically in adjacent normal colonic mucosae and primary adenocarcinomas. The effect of WNK1 on overall survival (OS) and its associations with the clinicopathological parameters were analyzed in a retrospective cohort of COAD patients (n = 185). The tumor-related effects of WNK1 in COAD were further tested via cellular and mice experiments.

Results: According to our cohort, higher WNK1 expression was significantly associated with unfavorable prognostic factors, such as high pT stage, pN stage, as well as shorter OS. Moreover, WNK1 exhibited tumor promoting role in COAD cancer cell lines as well as in nude mice. Silencing WNK1 can significantly inhibit the proliferation of COAD both in vitro and in vivo.

Conclusions: In all, WNK1 acts as a tumor promoter and may be used as a COAD prognostic biomarker.

Keywords: Colon adenocarcinoma; Prognosis; Proliferation; WNK1.

MeSH terms

  • Adenocarcinoma* / genetics
  • Adenocarcinoma* / metabolism
  • Animals
  • Colonic Neoplasms* / genetics
  • Colonic Neoplasms* / pathology
  • Humans
  • Mice
  • Mice, Nude
  • Prognosis
  • Retrospective Studies
  • WNK Lysine-Deficient Protein Kinase 1 / metabolism

Substances

  • WNK Lysine-Deficient Protein Kinase 1