Complete blood count-derived inflammation indices in colorectal cancer: head-to-head case-control and prognostic analyses with population reference intervals and external replication

Background Systemic inflammation drives cancer progression. We investigated the clinical utility of five routine complete blood count (CBC)-derived inflammatory biomarkers, neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), monocyte–lymphocyte ratio (MLR), systemic inflammation response index (SIRI), and systemic immune-inflammation index (SII), in colorectal cancer (CRC) patients. Methods We performed head-to-head case-control and prognostic analyses of five indices in 2305 CRC patients and 78,281 health‑screening controls, with replication in 1031 CRC patients. Analyses included propensity score matching, Cox regression, restricted cubic splines, and Harrell’s concordance index. Population reference intervals were derived, and cross‑population transferability was assessed using the National Health and Nutrition Examination Survey (NHANES). Results All indices were elevated in CRC patients and independently associated with survival. MLR retained diagnostic and prognostic significance in Stage I disease and was replicated. Dose–response trends were observed across quartiles, with non‑linear threshold effects for MLR and SIRI. Incremental prognostic gains beyond stage were modest. Reference intervals showed substantial overlap between CRC and healthy populations, limiting screening utility. NHANES comparison revealed non‑uniform transferability. Conclusion CBC‑derived indices demonstrated reproducible diagnostic and prognostic relevance, with MLR particularly informative in early‑stage CRC. Reference intervals contextualise abnormality but should not be interpreted as CRC screening or treatment thresholds.