High-risk Stage III colon cancer patients identified by a novel five-gene mutational signature are characterized by upregulation of IL-23A and gut bacterial translocation of the tumor microenvironment.

The heterogeneities of colorectal cancer (CRC) lead to staging inadequately of patients' prognosis. Here, we performed a prognostic analysis based on the tumor mutational profile and explored the characteristics of the high-risk tumors. We sequenced 338 colorectal carcinomas as the training dataset, constructed a novel five-gene (SMAD4, MUC16, COL6A3, FLG and LRP1B) prognostic signature, and validated it in an independent dataset from The Cancer Genome Atlas (TCGA). Kaplan-Meier and Cox regression analyses confirmed that the five-gene signature is an independent predictor of recurrence and prognosis in patients with Stage III colon cancer. The mutant signature translated to an increased risk of death (hazard ratio = 2.45, 95% confidence interval = 1.15-5.22, p = 0.016 in our dataset; hazard ratio = 4.78, 95% confidence interval = 1.33-17.16, p = 0.008 in TCGA dataset). RNA and bacterial 16S rRNA sequencing of high-risk tumors indicated that mutations of the five-gene signature may lead to intestinal barrier integrity, translocation of gut bacteria and deregulation of immune response and extracellular related genes. The high-risk tumors overexpressed IL23A and IL1RN genes and enriched with cancer-related bacteria (Bacteroides fragilis,Peptostreptococcus, Parvimonas, Alloprevotella and Gemella) compared to the low-risk tumors. The signature identified the high-risk group characterized by gut bacterial translocation and upregulation of interleukins of the tumor microenvironment, which was worth further researching.

Molecular characterization of the CD79a and CD79b and its role against Aeromonas hydrophila infection in Chinese sucker (Myxocyprinus asiaticus).

CD79a and CD79b heterodimers are the important signaling components of B cell receptor (BCR) complex which plays a crucial role in B cell development and antibody production. In the present study, CD79a and CD79b homologues from Chinese sucker (Myxocyprinus asiaticus), namely MaCD79a and MaCD79b, were identified and their expression at early developmental stages and under constitutive and stimulated conditions were investigated. The cDNA sequences for MaCD79a and MaCD79b contained open reading frame of 678 and 636 bp in length for 225 and 211 amino acid residues, respectively. The conserved features and important functional residues were found by sequence analysis. RT-PCR analysis revealed that transcripts of MaCD79s were detected in eggs and hatchling at 1-3 and 5-11 days post hatching (dph), but not detected at 13-17 and 19-27 dph, and constantly detected from 30 dph. Tissue distribution analysis showed that MaCD79s was most highly expressed in immune tissues, such as the spleen, head kidney, and kidney; the relatively low levels were detected in the heart, gill, and liver. Results of in situ hybridization also confirmed that MaCD79s is mainly expressed in systematic immune organs. Meanwhile, similar to IgM, MaCD79s-expressing cells in mucosal immune organ including the digestive track and gill were observed. Additionally, significant upregulation of MaCD79s was seen in the head kidney and spleen of Chinese sucker injected with Aeromonas hydrophila by quantitative real-time PCR. Taken together, our findings provided further information regarding fish CD79s gene and its role in adaptive immunity, which will contribute to the preservation and aquaculture of Chinese sucker.