ArticleFrontiers in oncology2026
Independent and sex-stratified association between microsatellite instability and peripheral hemoglobin in colorectal cancer.
Article in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Microsatellite instability (MSI) informs colorectal cancer (CRC) prognosis and treatment. Although anemia is common in CRC, whether peripheral hemoglobin (HB) differs according to MSI status independently of sex, tumor location, stage, and selected nutritional covariates remains unclear. This exploratory study evaluated the association between MSI status and HB and described sex-stratified discrimination within the study cohort. Methods: This retrospective study included 400 patients with stage II-III CRC. MSI-H status was inferred from four-protein mismatch repair immunohistochemistry. Multivariable logistic regression assessed HB as a continuous predictor after adjustment for sex, age, tumor location, TNM stage, albumin, body mass index, log-transformed C-reactive protein, hypertension, and diabetes. Sex-stratified receiver operating characteristic analyses evaluated HB alone and an expanded model, with 1, 000 bootstrap resamples for internal validation. Results: The cohort included 95 MSI-H and 305 microsatellite-stable patients. HB was lower in MSI-H patients of both sexes (both P < 0.001). Higher HB remained inversely associated with MSI-H status after adjustment (OR per 1-g/L increase = 0.977, 95% CI: 0.966-0.988; P < 0.001). The cohort-derived HB cutoffs were 125.0 g/L for males (AUC = 0.654) and 98.0 g/L for females (AUC = 0.693). Expanded-model apparent AUCs were 0.740 and 0.762, while bootstrap-corrected AUCs were 0.678 and 0.700, respectively. Conclusions: Lower HB was independently associated with MSI-H status, but its discrimination was modest and the expanded models showed optimism. HB may warrant further evaluation as an adjunctive signal, but it cannot replace tumor-based MMR/MSI testing. Prospective external validation is required.
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