Analysis of serum S100A12, soluble advanced glycation end products receptor, and gut microbiome in elderly patients with colorectal cancer

Abstract

Background: Colorectal cancer (CRC) ranks among the most prevalent malignancies in elderly populations, and chemotherapy resistance remains a critical clinical challenge. Emerging evidence highlights the interplay between chronic inflammation, gut microbiome dysbiosis, and CRC progression. Proinflammatory cytokines [e.g., interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α)] and mediators like S100 calcium-binding protein A12 (S100A12)/soluble receptor for advanced glycation end products (sRAGE) are implicated in tumorigenesis, while gut microbial imbalances may exacerbate inflammatory microenvironments conducive to chemotherapy resistance. However, the triad relationship between S100A12/sRAGE, gut microbiota profiles, and chemotherapy efficacy in elderly patients with CRC remains unexplored, limiting biomarker-driven therapeutic strategies.

Aim: To analyze the correlation between serum levels of S100A12, sRAGE, gut microbiome dysbiosis, and systemic inflammation in elderly patients with CRC and to assess their predictive value for chemotherapy efficacy.

Methods: A retrospective analysis was conducted on the clinical data of 120 elderly patients with advanced-stage CRC who visited our hospital from August 2023 to May 2024. These patients were enrolled in the study group. Additionally, 120 healthy individuals undergoing routine health check-ups during the same period were selected as the control group. Serum S100A12, sRAGE, IL-6, and TNF-α levels were measured by ELISA, and fresh stool samples were collected before chemotherapy to analyze gut microbiome composition in the study group. Follow-up observations were conducted after chemotherapy. Pearson correlation analysis was used to explore the relationship between serum S100A12, sRAGE levels, and gut microbiome dysbiosis in patients with CRC. The predictive diagnostic value of pre-chemotherapy serum S100A12 and sRAGE levels for chemotherapy efficacy was assessed using receiver operating characteristic curves.

Results: Pre-chemotherapy serum S100A12, sRAGE, IL-6, and TNF-α levels were significantly elevated in patients with CRC vs controls (all P < 0.05). These biomarkers progressively increased with microbiota dysbiosis severity (severe vs mild dysbiosis: S100A12: 340.26 ± 52.39 μg/L vs 302.53 ± 56.97 μg/L; sRAGE: 525.64 ± 37.32 ng/L vs 441.38 ± 48.73 ng/L, P < 0.05) and correlated strongly with IL-6 (r = 0.712) and TNF-α (r = 0.698). Post-chemotherapy, biomarker levels decreased (P < 0.05), coinciding with beneficial microbiota recovery (Bifidobacterium 176%, Lactobacillus 153%) and pathogenic taxa reduction (Escherichia coli 62%). The combined S100A12/sRAGE model predicted chemotherapy resistance with an area under the curve of 0.914 (sensitivity = 86.07%, specificity = 88.89%), outperforming individual biomarkers.

Conclusion: Elevated serum S100A12 and sRAGE in elderly patients with CRC reflected gut microbiome dysbiosis and systemic inflammation, driven by IL-6/TNF-α signaling. Their post-chemotherapy decline parallels microbiota restoration, supporting a microbiome-inflammation-biomarker axis. The combined biomarker model offers robust clinical utility for chemotherapy efficacy prediction and personalized therapeutic strategies.

Keywords: Chemotherapy efficacy; Colorectal cancer; Correlation; Elderly; Gut microbiome dysbiosis; Predictive value; Serum S100 calcium-binding protein A12; Soluble receptor for advanced glycation end products.

Figure 1

Comparison of serum S100 calcium-binding protein A12 and soluble receptor for advanced glycation end products levels before chemotherapy between the study and control groups. ^aP < 0.05. S100A12: S100 calcium-binding protein A12; sRAGE: Soluble receptor for advanced glycation end products; Control group: Healthy individuals; Study group: Elderly patients with colorectal cancer.

Figure 2

Comparison of serum S100 calcium-binding protein A12 and soluble receptor for advanced glycation end products levels before and after chemotherapy in patients with colorectal cancer. ^aP < 0.05. S100A12: S100 calcium-binding protein A12; sRAGE: Soluble receptor for advanced glycation end products.

Figure 3

Comparison of serum S100 calcium-binding protein A12 and soluble receptor for advanced glycation end products levels before chemotherapy in patients with colorectal cancer with different chemotherapy responses. ^aP < 0.05. S100A12: S100 calcium-binding protein A12; sRAGE: Soluble receptor for advanced glycation end products.

Figure 4

Receiver operating characteristic curve for the predictive diagnostic value of pre-chemotherapy serum S100 calcium-binding protein A12 and soluble receptor for advanced glycation end products levels for chemotherapy ineffectiveness in colorectal cancer. The receiver operating characteristic curve highlighted the superior predictive accuracy of the combined S100 calcium-binding protein A12/soluble receptor for advanced glycation end products model (green line) compared to individual biomarkers. The diagonal reference line (dashed line) represents random chance (area under the curve = 0.5). S100A12: S100 calcium-binding protein A12; sRAGE: Soluble receptor for advanced glycation end products.