Routine blood count ratios reveal inflammation fingerprints in colorectal cancer, with monocytes standing out in early disease

A simple calculation performed on an ordinary complete blood count — the cheap, universally ordered test that millions of people receive every year — may carry a surprising amount of information about colorectal cancer, according to one of the most comprehensive head-to-head comparisons of inflammation-derived blood ratios published to date. In a study appearing in the British Journal of Cancer, researchers in South Korea analysed five such indices in more than 2,300 colorectal cancer patients and nearly 78,300 healthy screening participants, then replicated their findings in an independent cohort of over 1,000 additional patients. Their conclusion is nuanced but striking: all five inflammation measures were reproducibly linked to both the presence of colorectal cancer and the odds of survival, yet one of them — the monocyte-to-lymphocyte ratio — stood apart as the only index that retained diagnostic and prognostic significance even in Stage I disease, the earliest and most curable stage.

The five indices examined are all built from the same raw ingredients: the absolute counts of neutrophils, lymphocytes, monocytes and platelets that pathologists already report on every complete blood count. The neutrophil-to-lymphocyte ratio (NLR) captures the balance between innate pro-inflammatory neutrophil activity and the lymphocyte-mediated adaptive immunity that normally patrols against tumours. The platelet-to-lymphocyte ratio (PLR) reflects platelet-driven prothrombotic and pro-angiogenic signalling relative to anti-tumour immunity. The monocyte-to-lymphocyte ratio (MLR) specifically gauges monocytic and myeloid-derived suppressor cell activation against lymphocyte surveillance. The two composite measures, the systemic inflammation response index (SIRI) and the systemic immune-inflammation index (SII), integrate multiple cell compartments into broader phenotypes of systemic inflammation. Because chronic systemic inflammation is recognised as an active driver of cancer progression and treatment resistance rather than a mere by-product, these ratios have attracted intense interest as potential low-cost prognostic tools.

What distinguishes the new analysis is its scale and methodological rigour. The research team drew colorectal cancer patients from Seoul National University Hospital, all of whom underwent curative-intent surgery between 2004 and 2008, excluding anyone who had received neoadjuvant chemoradiation, had prior colonic disease or had undergone previous colonic resection. The final cohort comprised 2,305 patients distributed across Stage I (626 patients, 27.1 percent), Stage II (759, 32.9 percent) and Stage III (920, 39.9 percent). Healthy controls came from 78,281 adults screened at the hospital’s Gangnam Center, each of whom had completed both complete blood count testing and colonoscopy, with anyone showing colonic pathology, inflammatory bowel disease or haematologic disorders excluded. Propensity score matching on age, sex, body mass index, smoking and alcohol consumption was used to place cancer patients and controls on comparable footing before diagnostic comparisons, and Cox proportional hazards regression, restricted cubic splines and Harrell’s concordance index quantified prognostic value and non-linear dose-response relationships.

The diagnostic results were consistent across all five indices. After propensity score matching and full adjustment, every ratio was significantly elevated in colorectal cancer patients compared with matched controls. On their native scales the effect sizes varied enormously — the monocyte-to-lymphocyte ratio produced a raw odds ratio of about 25, while the platelet-based indices yielded odds ratios barely above 1 — but the researchers showed that this disparity is largely an artefact of numerical scale rather than biology. When each index was standardised to a z-score and expressed per one-standard-deviation increment, the adjusted odds ratios converged to a similar range: 1.195 for NLR, 1.136 for PLR, 1.294 for MLR, 1.208 for SIRI and 1.179 for SII. On this common scale, the monocyte-to-lymphocyte ratio remained the strongest discriminator, and in Stage I disease it was one of only two indices — alongside NLR — whose standardised diagnostic association stayed statistically significant.

The prognostic findings followed a similar pattern. In fully adjusted survival models, all five indices were independently associated with overall survival, both as continuous variables and as binary high-versus-low categories defined by data-derived cutoffs (NLR 4.08, PLR 398.63, MLR 0.41, SIRI 2.59 and SII 1,923.75). Elevated PLR carried the largest binary hazard ratio at 3.956, followed by SII at 3.015 and SIRI at 2.528. Quartile analyses revealed persistent dose-response trends for NLR, MLR, SIRI and SII, with patients in the highest quartile facing adjusted hazard ratios of 1.541 to 2.129 relative to the lowest quartile. Restricted cubic spline modelling then uncovered two distinct risk geometries: NLR, PLR and SII showed approximately linear relationships with mortality, whereas MLR and SIRI exhibited non-linear, threshold-shaped curves in which risk rose steeply at lower values and then plateaued, suggesting that patients cross into a high-risk category beyond a critical point largely independent of further increases.

The most clinically provocative result concerned early-stage disease. Within the 626 Stage I patients, where the tumour burden is smallest and the inflammatory footprint would be expected to be faintest, the monocyte-to-lymphocyte ratio persisted as an independent prognostic marker even after adjustment for age, sex, body mass index and invasion characteristics, with a continuous-variable hazard ratio of 20.486 — a figure the authors caution carries a very wide confidence interval of 1.362 to 308.144, arguing for prospective evaluation rather than immediate changes to management. Expressed per standard deviation, the Stage I hazard ratio was a more interpretable 1.274. Crucially, this finding replicated in the external cohort of 1,031 patients from Korea’s National Cancer Center, where the monocyte-to-lymphocyte ratio again retained both diagnostic significance in Stage I disease (odds ratio 23.059) and prognostic significance (hazard ratio 17.342). The authors interpret this as evidence that the systemic inflammatory signature of early colorectal cancer is dominated by the monocytic and myeloid axis — possibly reflecting reduced immunosurveillance capability — rather than by neutrophil- or platelet-driven signals that become more prominent as tumour burden grows.

Yet the study is equally notable for what it declines to claim. By deriving population reference intervals from the enormous healthy screening cohort — following clinical laboratory standards for outlier handling and percentile estimation — the researchers positioned colorectal cancer values within the healthy distribution. The reference intervals were 0.82 to 3.94 for NLR, 72.2 to 249.6 for PLR, 0.101 to 0.379 for MLR, 168.0 to 1,034.8 for SII and 0.204 to 1.827 for SIRI. Although cancer patients were enriched above the healthy upper limit — 15.5 percent exceeded it for MLR and 13.5 percent for SIRI, compared with a reference expectation of 2.5 percent — the substantial majority of patients, between 84.5 and 93.1 percent depending on the index, remained within the population reference interval. The authors are explicit that these complete blood count-derived measures therefore cannot function as stand-alone colorectal cancer screening tests, and that a screening claim would require evaluation in a representative population with head-to-head comparison against established approaches such as faecal testing and colonoscopy.

A cross-population comparison using the US National Health and Nutrition Examination Survey added a further layer of caution. Among 19,536 eligible American adults with no cancer history, the Korean reference intervals transferred acceptably for NLR and SII, with only 6.6 and 7.1 percent of NHANES participants falling outside them, but transferability deteriorated sharply for the monocyte-containing indices: 13.7 percent of NHANES participants fell outside the Korean MLR interval and 15.1 percent outside the SIRI interval. Component blood counts revealed substantially higher neutrophil and monocyte counts in the US sample, suggesting the differences arise from the underlying analytical measurements rather than from a universal oncological threshold. The authors frame this as an assessment of reference-interval transferability rather than external validation, emphasising that percentile interpretation requires a population- and laboratory-compatible reference distribution.

The incremental prognostic value of the indices, measured by how much each improved discrimination when added to a baseline model of age, sex, body mass index and cancer stage, was honest about its own modesty. The baseline model achieved a mean concordance index of 0.699, and adding individual biomarkers yielded gains of only 0.002 to 0.008 in the original cohort — small absolute improvements, though statistically consistent across all five markers. In the replication cohort, the monocyte-to-lymphocyte ratio added the largest gain at 0.0137. The authors argue this is the appropriate evaluative criterion for low-cost, universally available biomarkers: not whether they supplant pathological stage as the dominant prognostic determinant, but whether they provide genuine risk stratification within stage, which these indices demonstrably do. With colorectal cancer ranking as the second leading cause of cancer-related mortality worldwide — roughly 1.9 million new cases annually, projected to reach 3.2 million by 2040 — the study supports these routine blood ratios as reproducible, scale-aware adjuncts for research risk stratification, while leaving their ultimate clinical value to prospective validation and to future studies testing whether modulating the inflammatory signals they capture can actually improve outcomes.

Subject of Research: Complete blood count-derived inflammation indices in colorectal cancer

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

Article References: Choe, E. K., Kim, M. J., Lee, D. W., Park, S. C., Sohn, D. K., Oh, J. H., Ryoo, S.-B., Jeong, S.-Y., Park, K. J., & Park, J. W. (2026). Complete blood count-derived inflammation indices in colorectal cancer: head-to-head case-control and prognostic analyses with population reference intervals and external replication. British Journal of Cancer. https://doi.org/10.1038/s41416-026-03647-z

Image Credits: AI Generated

DOI: 10.1038/s41416-026-03647-z

Keywords: colorectal cancer, complete blood count, systemic inflammation, monocyte-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, prognostic biomarkers, reference intervals, NHANES, early-stage cancer, British Journal of Cancer, Complete, blood