Abstract
Irinotecan (CPT11) is one of the most effective drugs for treating colon cancer, but its severe side effects limit its application. Recently, a traditional Chinese herbal preparation, named PHY906, has been proved to be effective for improving therapeutic effect and reducing side effects of CPT11. The aim of the present study was to provide novel insight to understand the molecular mechanism underlying PHY906-CPT11 intervention of colon cancer. Based on the GSE25192 dataset, for different three treatments (PHY906, CPT11, and PHY906-CPT11), we screened out differentially expressed genes (DEGs) and constructed a co-expression network by weighted gene co-expression network analysis (WGCNA) to identify hub genes. The key genes of the three treatments were obtained by merging the DEGs and hub genes. For the PHY906-CPT11 treatment, a total of 18 key genes including Eif4e, Prr15, Anxa2, Ddx5, Tardbp, Skint5, Prss12 and Hnrnpa3, were identified. The results of functional enrichment analysis indicated that the key genes associated with PHY906-CPT11 treatment were mainly enriched in ‘superoxide anion generation’ and ‘complement and coagulation cascades’. Finally, we validated the key genes by Gene Expression Profiling Interactive Analysis (GEPIA) and RT-PCR analysis, the results indicated that EIF4E, PRR15, ANXA2, HNRNPA3, NCF1, C3AR1, PFDN2, RGS10, GNG11, and TMSB4X might play an important role in the treatment of colon cancer with PHY906-CPT11. In conclusion, a total of 18 key genes were identified in the present study. These genes showed strong correlation with PHY906-CPT11 treatment in colon cancer, which may help elucidate the underlying molecular mechanism of PHY906-CPT11 treatment in colon cancer.
Highlights
Colon cancer is a common malignant tumor and the second leading cause of mortality worldwide in 2018 [1]
131 differentially expressed gene (DEG) were identified between Phosphate Buffered Saline (PBS) and CPT11, and 268 DEGs were identified between PBS and PHY906-CPT11, which indicated that the CPT11 and the PHY906-CPT11 administration both induced significant alterations in gene expression levels of colon tumors when compared with PBS treatment
The results showed that the GBP2, EIF4E, PRR15, ANXA2, HNRNPA3, NCF1, C3AR1, PFDN2, RGS10, GNG11, and TMSB4X were significantly dysregulated in SW480 cells after treating with PHY906-CPT11, which was similar with the above results
Summary
Colon cancer is a common malignant tumor and the second leading cause of mortality worldwide in 2018 [1]. Colon cancer development is related to many factors, such as age, sex, race/ethnicity, genetic makeup, dietary factors, increased BMI, red meat intake, low physical activity, long-term cigarette smoking (30–40 years), low vegetables and fruit consumption [2]. Studies showed that intestinal flora plays an important role in the occurrence and development of colon cancer [3]. Intestinal flora imbalance will cause damage to the intestinal barrier and impaired innate immune function, leading to inflammation and infection. Several studies have shown that colon cancer is closely related to inflammatory bowel disease (IBD) [7], and the relative risk of colon cancers in IBD patients is approximately two- to three-times greater than that in the general population. A number of studies have reported the importance of single
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