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Peer-reviewedCC BY 4.0Frontiers in Immunology

Explainable machine learning using pretreatment complete blood count parameters and demographic characteristics for gastric cancer risk stratification: a temporal validation study

  1. 1Department of Clinical Laboratory, Hanzhong Central Hospital, Hanzhong, Shaanxi, China.
  2. 2Department of Pathology, Hanzhong Central Hospital, Hanzhong, Shaanxi, China.
  3. 3Department of Surgical Oncology, Hanzhong Central Hospital, Hanzhong, Shaanxi, China.

Abstract

Background: Gastric cancer (GC) is often diagnosed at an advanced stage, while endoscopy is invasive and conventional serum tumour markers have limited sensitivity. A low-cost, widely available tool that can identify patients at higher risk and prioritise them for endoscopic evaluation could therefore strengthen early-detection pathways. The complete blood count (CBC) is routinely available and well suited to such first-contact risk stratification; however, existing CBC-based machine-learning models are often developed in cohorts that mix prevalent, postoperative, on-treatment and surveillance records, potentially confounding the haematological signal. We therefore developed and temporally validated an explainable CBC-based model to stratify the risk of newly diagnosed GC versus benign gastric disease in a rigorously verified, treatment-naïve cohort.

Methods: In this retrospective single-centre study, 2,044 patients (477 pathologically confirmed, newly diagnosed, treatment-naïve GC and 1,567 benign gastric-disease controls) were assembled through case-by-case chart review, patient-level identity de-duplication and application of the same prespecified comorbidity-screening criteria. The baseline CBC was obtained at admission before treatment. A parsimonious model incorporated six routinely available variables: age, sex, and neutrophil, lymphocyte, monocyte and platelet counts. Eight algorithms were trained using five-fold cross-validation in the training cohort (n = 1,309) and evaluated in a temporally separated validation cohort (n = 735). Random forest was designated as the reference explainable model and interpreted using SHAP. Model behaviour in tumour-marker-negative GC and robustness in sensitivity analyses were also assessed.

Results: Discrimination was similar across algorithms. In temporal validation, random forest achieved an AUC of 0.831 (95% CI 0.798–0.864), which was numerically similar to that of the highest-AUC model, XGBoost (AUC 0.832), with substantially overlapping 95% confidence intervals. Random forest had a low Brier score (0.133) and showed positive net benefit across the evaluated threshold-probability range. SHAP identified lymphocyte count, male sex and age as the leading predictors, with an identical feature ranking under XGBoost (Spearman ρ = 1.00). Adding derived inflammatory ratios did not improve discrimination (ΔAUC −0.010, p = 0.139). Among temporal-validation patients with triple-negative GC, defined as CEA-, CA19-9- and CA72-4-negative disease, the model classified 62.7% (95% CI 50.0–73.9) as high risk.

Conclusions: A six-variable model combining pretreatment CBC parameters with age and sex discriminated newly diagnosed GC from benign gastric disease in a temporally separated validation cohort and showed broadly acceptable graphical calibration and a low Brier score. The model classified a substantial proportion of tumour-marker-negative GC cases as high risk, supporting further evaluation as a low-cost pre-endoscopic triage aid. External multicentre validation is required.

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BibTeX
@article{qiao2026explainable,
  title = {{Explainable machine learning using pretreatment complete blood count parameters and demographic characteristics for gastric cancer risk stratification: a temporal validation study}},
  author = {Yongfeng Qiao and Qian Long and Jin Tang and Xin Wang and Shouli Wang},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1892111},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1892111/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Explainable machine learning using pretreatment complete blood count parameters and demographic characteristics for gastric cancer risk stratification: a temporal validation study
AU  - Yongfeng Qiao
AU  - Qian Long
AU  - Jin Tang
AU  - Xin Wang
AU  - Shouli Wang
PY  - 2026
DA  - 2026/10/15
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1892111
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1892111/full
AB  - Background: Gastric cancer (GC) is often diagnosed at an advanced stage, while endoscopy is invasive and conventional serum tumour markers have limited sensitivity. A low-cost, widely available tool that can identify patients at higher risk and prioritise them for endoscopic evaluation could therefore strengthen early-detection pathways. The complete blood count (CBC) is routinely available and well suited to such first-contact risk stratification; however, existing CBC-based machine-learning models are often developed in cohorts that mix prevalent, postoperative, on-treatment and surveillance records, potentially confounding the haematological signal. We therefore developed and temporally validated an explainable CBC-based model to stratify the risk of newly diagnosed GC versus benign gastric disease in a rigorously verified, treatment-naïve cohort.  Methods: In this retrospective single-centre study, 2,044 patients (477 pathologically confirmed, newly diagnosed, treatment-naïve GC and 1,567 benign gastric-disease controls) were assembled through case-by-case chart review, patient-level identity de-duplication and application of the same prespecified comorbidity-screening criteria. The baseline CBC was obtained at admission before treatment. A parsimonious model incorporated six routinely available variables: age, sex, and neutrophil, lymphocyte, monocyte and platelet counts. Eight algorithms were trained using five-fold cross-validation in the training cohort (n = 1,309) and evaluated in a temporally separated validation cohort (n = 735). Random forest was designated as the reference explainable model and interpreted using SHAP. Model behaviour in tumour-marker-negative GC and robustness in sensitivity analyses were also assessed.  Results: Discrimination was similar across algorithms. In temporal validation, random forest achieved an AUC of 0.831 (95% CI 0.798–0.864), which was numerically similar to that of the highest-AUC model, XGBoost (AUC 0.832), with substantially overlapping 95% confidence intervals. Random forest had a low Brier score (0.133) and showed positive net benefit across the evaluated threshold-probability range. SHAP identified lymphocyte count, male sex and age as the leading predictors, with an identical feature ranking under XGBoost (Spearman ρ = 1.00). Adding derived inflammatory ratios did not improve discrimination (ΔAUC −0.010, p = 0.139). Among temporal-validation patients with triple-negative GC, defined as CEA-, CA19-9- and CA72-4-negative disease, the model classified 62.7% (95% CI 50.0–73.9) as high risk.  Conclusions: A six-variable model combining pretreatment CBC parameters with age and sex discriminated newly diagnosed GC from benign gastric disease in a temporally separated validation cohort and showed broadly acceptable graphical calibration and a low Brier score. The model classified a substantial proportion of tumour-marker-negative GC cases as high risk, supporting further evaluation as a low-cost pre-endoscopic triage aid. External multicentre validation is required.
SN  - 1664-3224
ER  -