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

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.