SIRT1 Expression in Human Gastrointestinal Tumors and Its Clinical Significance

Objective

This study aimed to investigate the expression levels of SIRT1 protein in gastric (GC), colon (CC), and rectal cancer (RC) tissues and patient plasma, analyze its correlation with clinicopathological features and prognosis, and preliminarily explore its relationship with the tumor immune microenvironment.

Methods

Plasma samples were collected from 198 gastrointestinal cancer patients (66 each of GC, CC, and RC) and 66 healthy volunteers. Additionally, cancerous and adjacent normal tissues were obtained from 45 of these patients (15 pairs for each cancer type). SIRT1 concentration in plasma was detected using Enzyme-Linked Immunosorbent Assay (ELISA). SIRT1 protein expression in tissues was examined using Immunohistochemistry (IHC) and Western Blotting. Bioinformatic analysis was performed using TCGA and GEPIA databases. The correlation between SIRT1 and immune cell infiltration was analyzed via the TIMER database. Statistical analyses were conducted using SPSS software.

Results

Plasma SIRT1 concentration was significantly higher in the GC group compared to healthy controls (p = 0.045), while it was significantly lower in the CC and RC groups (p = 0.007 and p = 0.009, respectively). In tissues, SIRT1 expression was up-regulated in GC but down-regulated in colorectal cancer (CC and RC) tissues (p < 0.05). SIRT1 expression levels were significantly correlated with clinicopathological features including tumor differentiation degree, depth of invasion, TNM stage, distant metastasis (in colorectal cancer), and lymph node metastasis (in RC) (p < 0.05). Survival analysis revealed that high SIRT1 expression was associated with poorer overall survival (OS) in GC patients (p = 0.032), while low expression was associated with poorer OS in RC patients (p = 0.027). Plasma SIRT1 levels showed significant correlations with various tumor markers (e.g., CEA, CA199, CA125, CA724). Furthermore, SIRT1 expression was positively correlated with the infiltration levels of immune cells such as CD4+ T cells, CD8+ T cells, macrophages, and neutrophils.

Conclusion

SIRT1 expression in gastrointestinal tumors is tissue-specific (upregulated in GC, downregulated in colorectal cancer). Its expression level is closely associated with malignant progression and patient prognosis, and it may be involved in the modulation of the tumor immune microenvironment. SIRT1 shows promise as a potential diagnostic biomarker and therapeutic target for gastrointestinal cancers.