QS219 - Preoperative and intraoperative local and systemic immuno-inflammatory markers as predictors of colorectal cancer recurrence after surgery

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Purpose/Background: Colorectal cancer (CRC) is a major public health concern, with recurrence after surgery being a leading cause of morbidity and mortality. Clinical staging and pathological assessment are commonly used to assess tumor biology and recurrence risk, but data on biomarkers for recurrence are limited. Studies, including our own, have shown that the gut microenvironment—especially the microbiome—may influence immune and inflammatory responses and potentially affect CRC recurrence. Our objective is to identify preoperative or intraoperative biomarkers to predict colorectal cancer recurrence.

Methods/Interventions: We conducted a prospective cohort study in patients with CRC undergoing surgery with curative intent. Fecal samples were collected before surgery, and intraoperative healthy colorectal mucosal samples were obtained from the freshly retrieved surgical specimen. Samples were frozen at -80°C. A complete blood count was available preoperatively for all patients. A multiplex panel was used to quantify nine inflammatory cytokines in mucosal samples: IFN-γ, IL-10, IL-1β, IL-5, TNF-α, IL-17A/F, MCP-1, MIP-1α, and MIP-2. Calprotectin, lipocalin-2 (an antimicrobial peptide), and several bacterial pro-carcinogenic genes (polyketide synthetase, Bacteroides fragilis toxin, and FadA) were quantified in fecal samples. Patients were followed postoperatively, and overall survival (OS) and disease-free survival (DFS) were computed using univariate and multivariate analyses, adjusting for age, sex, body mass index, and cancer stage.

Results/Outcomes: Seventy-two patients with CRC—44 males and 28 females—were recruited and followed after surgery for a median period of 34 months. Fifteen patients (21%) experienced local or distant recurrence. In preoperative fecal samples, higher levels of calprotectin and lipocalin-2 were associated with lower DFS on multivariate analysis (P=0.03 and 0.04, respectively). In preoperative blood samples, higher monocyte and lymphocyte counts were also associated with lower DFS (P=0.001 and 0.03, respectively). In intraoperative mucosal samples, TNF-α was associated with lower DFS on multivariate analysis (P=0.03). No markers were associated with OS. We then combined these 5 markers (calprotectin, lipocalin-2, TNF-α, monocytes, and lymphocytes) associated with lower DFS to calculate a composite score. Using a receiver operating characteristic (ROC) curve, a cutoff value of 1278 with the highest sensitivity and specificity was identified and used to predict postoperative recurrence with high accuracy (Figure 1).

Conclusion/Discussion: In this project, we identified new links between local and systemic inflammatory markers and disease-free survival (DFS) in CRC surgery patients. Our previous work showed that the gut microbiome can lead to low-grade inflammation, weakening gut barrier function and promoting cancer cell spread during surgery and postoperative metastasis. Consistent with these findings, our data suggests that monitoring low-grade inflammation in fecal, blood, and tissue samples may help predict CRC patients at higher risk of poor outcomes. Prospective validation is underway in our Biobank of Digestive Diseases to confirm these markers' role in predicting recurrence. These results pave the way for personalized treatments, identifying patients who may potentially benefit from neoadjuvant and adjuvant therapies.