Age-Dependent Prognostic Significance of Preoperative Transthyretin After Curative Resection for Stage I-III Colorectal Cancer.

Abstract

Background: Preoperative malnutrition and systemic inflammation are established determinants of adverse outcomes in colorectal cancer (CRC). Transthyretin (TTR), a rapid-turnover hepatic protein, reflects both nutritional and inflammatory status; however, its clinical utility may be influenced by age- and sex-related variability. This study evaluated the prognostic significance of preoperative TTR in patients undergoing curative resection for stage I-III CRC.

Methods: A retrospective cohort of 536 patients who underwent curative resection for stage I-III CRC between 2014 and 2024 at a single institution was analyzed. Sex-specific TTR cutoffs were derived using survival classification and regression tree analysis (20.9 mg/dL for men; 16.95 mg/dL for women), and patients were stratified into low- and high-TTR groups. The primary endpoint was recurrence-free survival (RFS). Survival outcomes were assessed using Kaplan-Meier analysis, multivariable Cox proportional hazards modeling, and age-stratified analyses.

Results: Preoperative TTR levels were lower in women and demonstrated a progressive decline with increasing age. Patients with low TTR exhibited significantly inferior RFS compared with those with high TTR (log-rank p < 0.0001). In multivariable analysis, low preoperative TTR remained an independent predictor of worse RFS (HR 2.407, 95% CI 1.625-3.566; p < 0.001). Age-stratified analyses demonstrated that the prognostic impact of low TTR was most pronounced in younger patients and progressively attenuated with advancing age.

Conclusions: Preoperative TTR represents an independent prognostic biomarker following curative resection for stage I-III CRC. Its prognostic utility is age-dependent, with greatest relevance in younger patients, supporting interpretation within an age- and sex-specific framework.