Comprehensive analysis based on tertiary lymphoid structures and tumor budding predicts survival rates in colorectal cancer patients with synchronous liver metastases

Background Synchronous colorectal cancer liver metastasis (CRCLM) is closely associated with poor prognosis; however, the precise factors contributing to this adverse outcome remain uncertain. In the tumor microenvironment of CRCLM, tumor budding (TB) serves as a morphologic hallmark of invasive potential, while tertiary lymphoid structures (TLS) are indicative of organized anti-tumor immune contexture. This study aimed to integrate these biomarkers to predict the survival of patients with CRCLM. Methods This multicenter retrospective study enrolled 107 patients with synchronous CRCLM who underwent curative resection for colorectal cancer. An external validation cohort including 30 patients with CRCLM were also employed. The density of TLS and the TB count were quantified via hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining on primary tumor specimens. Relationships between clinicopathological data, overall survival (OS), and recurrence-free survival (RFS) were analyzed. The TLS/TB index was derived by integrating TLS and TB densities. The clinical role and prognostic value of the TLS/TB index in patients with CRCLM were analyzed, and a nomogram was constructed to predict the 3-year survival of patients. Results High TLS density was significantly associated with prolonged overall survival (OS; p < 0.001) and recurrence-free survival (RFS; p< 0.001) in patients with CRCLM. Conversely, higher TB grade predicted a worse OS (p < 0.001) and RFS (p < 0.001). The TLS and TB exhibited a significant inverse correlation (r = -0.581, p < 0.001). The TLS/TB index demonstrated superior prognostic accuracy in the training cohort (AUC = 0.89) compared with histological differentiation (AUC = 0.70), TB grade (AUC = 0.85) and TLS density (AUC = 0.80), with consistent performance in the validation cohort. Calibration curves showed acceptable agreement between predicted and observed survival in both cohorts. Conclusion These results demonstrated that tumor budding and tertiary lymphoid structures are inversely correlated in CRCLM. Furthermore, the TLS/TB-based nomogram may effectively enhanced the accuracy of prognosis prediction in patients with CRCLM, potentially facilitating the formulation of individualized treatment strategies.