KLK10 Upregulation Drives Aggressiveness and Radioresistance and Has a Negative Prognostic Impact on Rectal Cancer

Area of Science:

• Oncology
• Biochemistry
• Molecular Biology

Background:

• Rectal cancer treatment response is highly variable, lacking reliable biomarkers beyond TNM staging.
• Personalized treatment for rectal cancer is limited by the absence of predictive efficacy markers for concurrent chemoradiotherapy (CCRT).
• Serine proteases, involved in extracellular matrix degradation, are implicated in tumor progression.

Purpose of the Study:

• To investigate kallikrein-related peptidase 10 (KLK10) as a potential biomarker for predicting CCRT response in rectal cancer.
• To assess the association of KLK10 with clinicopathologic features and patient survival outcomes following preoperative CCRT.
• To explore KLK10's role in rectal cancer progression and radiation resistance.

Main Methods:

• Analysis of KLK10 immunoreactivity in a cohort of 343 rectal cancer patients.
• Correlation of KLK10 levels with clinicopathologic characteristics (nodal status, tumor stage, invasion, regression).
• Multivariate survival analyses for disease-specific, locoregional recurrence-free, and metastasis-free survival.
• Cellular assays to determine KLK10's functional role in cancer progression and radiation resistance.

Main Results:

• High KLK10 immunoreactivity was significantly associated with adverse features: advanced nodal status, higher tumor stage, perineural/vascular invasion, and poor regression post-CCRT.
• Elevated KLK10 independently predicted worse outcomes: lower disease-specific survival (HR 3.65), reduced locoregional recurrence-free survival (HR 3.59), and poorer metastasis-free survival (HR 2.46).
• Cellular studies indicated KLK10 promotes aggressive phenotypes and enhances radiation resistance in rectal cancer cells.

Conclusions:

• KLK10 serves as a significant predictive and prognostic biomarker in rectal cancer patients undergoing CCRT.
• High KLK10 expression is linked to aggressive disease characteristics and inferior survival outcomes.
• KLK10 represents a potential therapeutic target for improving rectal cancer treatment efficacy and overcoming radiation resistance.