Prognostic Significance of STK11/LKB1 Expression and Its Role in the Tumor Microenvironment of Colorectal Adenocarcinoma

Abstract

Background/aim: The loss or mutation of serine-threonine kinase 11/liver kinase B1 (STK11/LKB1) is known to negatively impact prognosis and immunotherapy outcomes in non-small cell lung cancer (NSCLC), and germline mutations in this gene cause gastrointestinal adenocarcinomas in patients with Peutz-Jeghers syndrome (PJS). Although STK11/LKB1 mutations are rare in colorectal cancer, the down-regulation of STK11/LKB1 has been implicated in its tumorigenesis. However, the relationship between STK11/LKB1 expression and the immunosuppressive tumor microenvironment in colorectal cancer remains unclear.

Materials and methods: In this study, we collected tissues from patients with colorectal adenocarcinoma (COAD) and constructed tissue microarrays (TMAs). STK11/LKB1 expression was assessed by immunohistochemistry and quantified by calculating H-scores. We also examined subsets of intratumoral tumor-infiltrating lymphocytes (TILs), including CD45+, CD8+, PD-1+, and CD45RO+ TILs, in these TMAs.

Results: STK11/LKB1 expression was significantly correlated with nodal metastasis. Kaplan-Meier survival analysis demonstrated that low STK11 expression was associated with significantly poorer overall survival (OS), particularly in COAD patients with KRAS mutations. However, STK11/LKB1 expression was not correlated with the presence of intratumoral CD45+, CD8+, PD-1+, or CD45RO+ TILs. Finally, multivariate Cox proportional regression analysis identified STK11/LKB1 expression as an independent prognostic factor in COAD patients.

Conclusion: While STK11/LKB1 expression is associated with tumor progression and survival outcomes, there is no evidence that STK11/LKB1 expression influences the infiltration of lymphocytes into the tumor microenvironment.

Keywords: STK11/LKB1 expression; colorectal adenocarcinoma; prognosis; tumor microenvironment; tumor-infiltrating lymphocytes.