Analysis and exploration of the association between serum tumor marker status and clinical pathological features, as well as efficacy, in colorectal cancer.

Colorectal cancer (CRC) remains a major global health challenge, necessitating improved prognostic and predictive tools. The aim of the present study was to investigate the associations between elevated serum tumor markers (TMs) and clinicopathological features in patients with colorectal cancer, to evaluate their prognostic ability in advanced-stage disease cases and to identify patients most likely to respond to treatment. This retrospective study analyzed data from 293 patients treated for colorectal adenocarcinoma between January 1, 2020, and June 30, 2023. Carcinoembryonic antigen and cancer antigen (CA)19-9, CA72-4 and CA125 positivity were evaluated to classify patients into negative, single elevation (higher expression than normal in 1 TM) and multiple elevation (≥2 TMs expressed at higher than normal levels) groups. Clinical characteristics were evaluated using χ tests, and a Kaplan-Meier survival analysis was conducted. The number of elevated TMs was associated with T stage (P=0.01), poor differentiation (P<0.001), later clinical stages (P<0.001), metastatic sites (P<0.001) and larger metastatic diameter (P<0.001). TM elevation was not associated with the N stage, primary site and microsatellite instability status (MSI) status, or the objective response rate and disease control rate after first-line treatment. Having multiple TM elevations was associated with poorer progression-free survival (PFS). With regard to non-MSI-H/deficient mismatch repair (dMMR) [immune checkpoint inhibitor (ICI) + tyrosine kinase inhibitor (TKI)] therapy, the single TM elevation dMMR patient group receiving third-line ICI + TKI benefited the most, regardless of tumor burden, especially those with a neutrophil-to-lymphocyte ratio (NLR) <3. In conclusion, multiple TM elevations were associated with the T stage, poor differentiation, later clinical staging, metastatic site, tumor burden and worse PFS. Non-MSI-H/dMMR patients with single TM elevations benefited most from ICI + TKI therapy, particularly those with an NLR <3.