Molecular profiling analysis for colorectal cancer patients with Pi-Xu or Shi-Re syndrome

BACKGROUND: Traditional Chinese medicine (TCM) syndromes (ZHENG in Chinese) constitute the basis of understanding the disorders of patients and guiding the use of the Chinese herbs. Colorectal cancer is divided into various subtypes mainly according to the ZHENG identification. OBJECTIVE: We aimed to determine the molecular basis underlying Pi-Xu (spleen deficiency) and Shi-Re (dampness-heat) ZHENG that are commonly found in colorectal cancer patients. METHODS: About 80 colorectal cancer patients, including 47 Pi-Xu ZHENG and 33 Shi-Re ZHENG were enrolled. Blood and tissue samples of these patients were available for protein and mRNA expression. The protein expression was determined by Immunohistochemistry (IHC) staining and mRNA profiling was detected by expression microarray. Furthermore, mRNA fold change was evaluated by qRT-PCR. RESULTS: The colorectal cancer patients with Shi-Re ZHENG had a poor prognosis, compared with Pi-Xu ZHENG (95% CI: 0.05–0.33; p < 0.0001). Moreover, there was a significant difference in protein expression levels (especially for mutant TP53, PCNA, PD-L1 and Ki-67) among Pi-Xu and Shi-Re ZHENG (p < 0.01). Meanwhile, mRNA expression (especially for wild type TP53, KDM6A, PCNA, PD-L1, Ki-67, CCL-2, IL-1a and COX-2) was also remarkably different between Pi-Xu and Shi-Re groups (p < 0.01). CONCLUSION: Our results suggest that Shi-Re ZHENG conditions may contribute to poor overall survival in patients with colorectal cancer. Compared with Pi-Xu ZHENG, high expression of mutant TP53, PCNA, PD-L1, Ki-67, CCL-2, IL-1a and COX-2 may serve as potential biomarkers for diagnosis and prognosis of colorectal cancer patients displayed Shi-Re ZHENG.