Search

Fluoropyrimidine-based chemotherapy is an essential component of systemic chemotherapy for colorectal cancer (CRC). The immune response is implicated in chemotherapy-induced cytotoxicity. Here, we reported an immune risk (Imm-R) model for prognostic prediction in patients receiving fluoropyrimidine-based chemotherapy. Gene expression profiles and corresponding clinical information were collected from four data sets and divided into training set (n = 183) and validation set (validation set1: n = 34; validation set2: n = 99). The composition of 22 tumor-infiltrating immune cells (TIICs) populations was characterized with the CIBERSORT deconvolution algorithm. A prognostic Imm-R model for predicting overall survival was established by performing least absolute shrinkage and selection operator (LASSO) penalized COX regression analysis. T follicular helper cells and M0 macrophages were associated with better survival, while eosinophils were associated with worse survival. TIICs signature was constructed based on the above three immune cell types. Furthermore, a Imm-R model was created by integrating TIICs signature with immune-related genes (IRGs), which effectively in distinguishing CRC patients with poorer prognosis. The Imm-R model was associated with activation of the TGF-beta signaling and suppression of DNA damage. Results of this research provide new insights into the role of immunity for in fluoropyrimidine-based chemotherapy as well as a useful tools to predict the outcome of CRC patients receiving fluoropyrimidine-based chemotherapy. [ABSTRACT FROM AUTHOR]

To explore the spectrum of p53 gene mutations of sporadic colorectal carcinoma in Guangxi, a Zhuang autonomous region in southern China, we examined exons 2&nvsim; 11 and exon-intron junctions of p53 gene from 48 patients with sporadic colorectal carcinoma by using single strand conformation polymorphism (SSCP) and DNA direct sequencing. As a result, p53 gene mutations were found in 31.25 percent (15/48) of our patients. A total of 13 types of p53 gene mutations were found, namely, c.370T > G, c.524G > A, c.528C > G, c.529_546del18, c.536A > G, c.736A > G, c.743G > A, c.770_771del2, c.772G > T, c.814G > A, c.949delC, c.782+1G > A, and c.919+1G > C. Only a double heterozygote for c.370T > G and c.529_546del18 was found. All the other mutations were heterozygous. No homozygote was found. 524G > A was the most common mutation, accounting for 18.75 percent (3/16). c.370T > G could not be found in the whole somatic mutation section of IARC TP 53 mutation database (2004 version). c.528C > G, c.949delC, c.782+1G > A, and c.919+1G > C could not be found in colorectal carcinomas reported in the somatic mutation section of IARC TP 53 mutation database (2004 version). The frequency (45.83 percent) of p53 gene mutations in &nvge;60 years old patients was higher than that (16.67 percent) in < 60 year old patients (P < 0.05). The frequency (47.83 percent) of p53 gene mutations in rectal carcinoma was higher than that (16 percent) in colonic carcinoma (P < 0.025). [ABSTRACT FROM AUTHOR]