High Intelectin-1 Expression Associated with Aggressive Tumor Behavior and Worse Survival in Rectal Cancer

Background: Multimodal treatment involving preoperative chemoradiotherapy (CRT) followed by surgery is the current standard of care for rectal cancer. Despite advancements, the risk of recurrence, metastasis, and decreased survival remains high. This study aims to evaluate potential biomarkers to stratify prognosis in patients with rectal cancer undergoing preoperative CRT and surgery. Methods: Through data mining of receptor-binding pathways in a published transcriptome for rectal cancer cases, ITLN1 was identified as the most relevant gene associated with poor response to chemoradiation (GO:0005102). Rectal cancer specimens (n = 343) collected between 1998 and 2017 were analyzed for ITLN1 expression using immunohistochemistry. The association between ITLN1 protein expression and clinicopathological features was assessed using Pearson's chi-square test. Survival outcomes based on ITLN1 expression were evaluated using the Kaplan-Meier method and compared with Log rank tests. Results: ITLN1 immunoreactivity was significantly elevated in rectal tumor tissues. High ITLN1 expression was strongly associated with adverse clinicopathological features, including advanced post-treatment tumor status (T3-4; p = 0.001), post-treatment nodal status (N1-2; p < 0.001), vascular invasion (p = 0.017), perineural invasion (p = 0.001), and a lower degree of tumor regression (p = 0.009). Uni- and multivariable analyses revealed that high ITLN1 expression correlated with poorer disease-specific survival, local recurrence- free survival, and distant metastasis-free survival compared to low ITLN1 expression. Conclusion: Elevated ITLN1 expression is significantly associated with aggressive tumor behavior and unfavorable survival outcomes in rectal cancer. These findings highlight ITLN1 as a potential prognostic biomarker and provide a foundation for future research into its role in rectal cancer progression and treatment response.