Frontiers in genetics · 2026
Tumor-immune microenvironment and nutritional status biomarkers predict recurrence after total colectomy for locally advanced colon cancer: development and internal validation of a nomogram.
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Zhang Yong-Qing, Huang Ming, Jia Xiao-Yan, Zou Ya-Fen, Chen Dan
Аннотация
BACKGROUND: Post-colectomy recurrence affects 25%-45% of patients with locally advanced colon cancer despite adjuvant chemotherapy. The tumor-immune microenvironment (TIME)-encompassing mismatch repair (MMR) status, tumor-infiltrating lymphocyte (TIL) density, PD-L1 expression, and systemic indices such as the neutrophil-to-lymphocyte ratio (NLR)-critically determines recurrence risk and immunotherapy response. Perioperative nutritional status (preoperative albumin; NRS 2002) further modulates immune competence. No validated clinical tool has integrated these multi-dimensional biomarkers for post-colectomy risk stratification.
METHODS: This retrospective dual-centre cohort enrolled 341 patients (stage II-III colon cancer; total colectomy, 2020-2024). Tumour-immune biomarkers (MMR/MSI status, PD-L1 CPS, TIL density, NLR, PLR) and nutritional indicators (albumin, NRS 2002) were assessed preoperatively. Primary endpoint: 3-year disease-free survival (DFS). A nomogram was constructed from multivariable Cox regression and internally validated by 1,000-resample bootstrapping; performance was assessed by AUC, calibration, and decision curve analysis.
RESULTS: Among 341 patients (median follow-up 36.0 months), 94 (27.6%) recurred; 3-year DFS was 72.4%. Independent predictors of inferior DFS: pMMR/MSS status (aHR = 2.84), advanced stage (aHR = 2.52), high lymph node ratio (aHR = 2.13), low TIL density (aHR = 2.21), elevated CEA (aHR = 1.88), and high NLR (aHR = 1.78; all p ≤ 0.008). Preoperative albumin (aHR = 0.94 per 1 g/L increase, p = 0.003) and NRS 2002 >=4 (aHR = 1.58, p = 0.035) also remained independently associated with DFS. Adjuvant ICI use was associated with improved DFS (aHR = 0.48, p = 0.005). The nomogram achieved AUC = 0.841 (optimism-corrected: 0.824), good calibration (Hosmer-Lemeshow p = 0.557), and net clinical benefit across threshold probabilities 0.10-0.80.
CONCLUSION: A nomogram integrating MMR status, TIL density, PD-L1 CPS, NLR, CEA, tumour stage, lymph node ratio, and perioperative nutritional indicators robustly predicts 3-year recurrence after total colectomy for locally advanced colon cancer (AUC = 0.841), substantially outperforming clinical-only models. These hypothesis-generating findings require prospective randomised validation before clinical implementation.
METHODS: This retrospective dual-centre cohort enrolled 341 patients (stage II-III colon cancer; total colectomy, 2020-2024). Tumour-immune biomarkers (MMR/MSI status, PD-L1 CPS, TIL density, NLR, PLR) and nutritional indicators (albumin, NRS 2002) were assessed preoperatively. Primary endpoint: 3-year disease-free survival (DFS). A nomogram was constructed from multivariable Cox regression and internally validated by 1,000-resample bootstrapping; performance was assessed by AUC, calibration, and decision curve analysis.
RESULTS: Among 341 patients (median follow-up 36.0 months), 94 (27.6%) recurred; 3-year DFS was 72.4%. Independent predictors of inferior DFS: pMMR/MSS status (aHR = 2.84), advanced stage (aHR = 2.52), high lymph node ratio (aHR = 2.13), low TIL density (aHR = 2.21), elevated CEA (aHR = 1.88), and high NLR (aHR = 1.78; all p ≤ 0.008). Preoperative albumin (aHR = 0.94 per 1 g/L increase, p = 0.003) and NRS 2002 >=4 (aHR = 1.58, p = 0.035) also remained independently associated with DFS. Adjuvant ICI use was associated with improved DFS (aHR = 0.48, p = 0.005). The nomogram achieved AUC = 0.841 (optimism-corrected: 0.824), good calibration (Hosmer-Lemeshow p = 0.557), and net clinical benefit across threshold probabilities 0.10-0.80.
CONCLUSION: A nomogram integrating MMR status, TIL density, PD-L1 CPS, NLR, CEA, tumour stage, lymph node ratio, and perioperative nutritional indicators robustly predicts 3-year recurrence after total colectomy for locally advanced colon cancer (AUC = 0.841), substantially outperforming clinical-only models. These hypothesis-generating findings require prospective randomised validation before clinical implementation.