Purpose: The prognosis for colorectal cancer (CRC) patients is drastically impacted by the presence of lymph node or liver metastases at diagnosis or resection. On this basis it is sought to identify novel proteins as biomarkers and determinants of CRC metastasis. Experimental Design: Proteomic analyses are undertaken using primary tissues from ten Chinese CRC patients presenting with or without liver metastases and immunohistochemistry used to validate selected proteins in an independent patient cohort. Results: Comparing CRC against paired normal adjacent tissues identifies 1559 differentially expressed proteins (DEPs) with 974 upregulated and 585 downregulated proteins, respectively. The highest number of DEPs is selectively associated with metastatic tumors (519 upregulated and 267 downregulated proteins, respectively) with a smaller number of unique DEPs identified only in non-metastatic CRC cases (116 upregulated and 29 downregulated proteins, respectively). The remaining DEPs are commonly expressed in both non-metastatic and metastatic tumors. The upregulation of three representative DEPs (S100A11, S100P, and RBM25) is confirmed using immunohistochemistry against 154 CRC tissues embedded in a tissue microarray. Conclusions and Clinical Relevance: The data reveal both previously identified CRC biomarkers along with novel candidates which provide a ready resource of DEPs in CRC for further investigation.

Spliceosomes are large RNA-protein molecular complexes which mediate splicing of pre-mRNA in eukaryotic cells. Their function is frequently altered in cancer, providing opportunities for novel therapeutic approaches. The ubiquitin specific protease 39 (USP39) is a highly conserved deubiquitylation family member that plays an essential role in pre-mRNA splicing where it serves to assemble the mature spliceosome complex. Previous studies have reported that USP39 acts in an oncogenic manner where it contributes to cancer progression and predicts poor prognosis in various human tumor types. Here we report that USP39 is differentially upregulated in human esophageal squamous cell carcinoma (ESCC) and its expression is significantly associated with clinicopathological characteristics including differentiation status and TNM stage. We found the USP39 upregulation was maintained in ESCC cell lines where it functioned to promote cancer cell growth in vitro and in xenografts. RNA-seq analyses identified that mTOR pathway activation was affected by shRNA-mediated silencing of USP39. Subsequent biochemical analyses demonstrated that USP39 regulates the activity of mTORC2 by selectively enhancing the splicing and maturation of Rictor mRNA, although not other key mTORC components. Together, our report proposes USP39 as a biomarker and oncogenic factor in ESCC, with a potential for targeting the USP39/mTOR2/Rictor axis as a therapeutic strategy. Furthermore, our study adds ESCC to the list of cancers where USP39 contributes to tumorigenesis and progression.

No abstract

Vaginal and cervical canal bacteria are associated with women’s health and pregnancy outcomes. Here, we compared their composition and characteristics in 37 reproductive-aged Chinese women including 24 pregnant women with cervical incompetence (vaginal and cervical canal bacteria formed Groups A and B, respectively) and 13 healthy pregnant women (vaginal and cervical canal bacteria formed Groups C and D, respectively) using high-throughput sequencing of the V4 region of 16S rRNA gene. The results of alpha and beta diversity analysis, respectively, indicated no statistical differences between Groups A and B (p = 0.32, 0.06), nor Groups B and D (p = 0.69, 0.74); however, differences were found between Groups C and D (p = 0.02, 0.01) and between Groups A and C (p = 0.04, 0.02). PLS-DA analysis showed that the individuals from each group were irregularly distributed according to their clade. Lactobacillus, Bifidobacterium and Ureaplasma were the dominant genera in all groups. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSts) analysis identified 31 Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologs associated with the bacterial communities from the four groups, including membrane transport, folding, sorting and degradation, xenobiotics biodegradation and metabolism, and nucleotide metabolism. We further determined relationships between pregnancy outcomes (Apgar scores) and certain bacterial species. A significant positive correlation was found between Apgar scores and Actinomyces neuii and Anoxybacillus flavithermus in the vagina and cervical canal of pregnant women with cervical incompetence while Bacteroides plebeius, Bifidobacterium pseudopodium and Staphylococcus petrasii in the cervical canal displayed negative correlations with Apgar scores. Moreover, Clostridium fimetarium, Methanobacterium congolense, Pseudomonas chlororaphis, and Psychrobacter nivimaris in the vagina were negatively correlated with Apgar scores. These bacteria may serve as potential biomarkers, however, additional research is warranted to verify their role in clinical outcomes.

No abstract

Mitochondrial DNA (mtDNA) mutations play crucial roles in the pathogenesis and progression of human malignancies. However, studies reporting associations between mitochondrial DNA mutations and risks of esophageal squamous cell carcinomas (ESCC) have seldom been reported. In this study, we sequenced 22 cancer tissues and the corresponding adjacent non-cancerous tissues collected from 11 ESCC patients. The mtDNA sequence length ranged from 16,568-16,579 bp. The results indicated that there are several sensitive sites in the 22 mtDNAs, especially in the control region (CR) and protein-coding genes (PCGs). The 22 mtDNA sequences were classified into haplogroups B, D, G, M, and Z; haplogroup D and haplogroup M were shared within a wider distribution, but haplotype G was found only in two samples and all the patients showed the southern of East Asia or Northern East Asian haplogroups, the number and ratio of patients showed the southern of East Asia or Southeast Asia characters are equal. Our findings suggest that mtDNA haplogroups D and M might be potential risks for ESCC. In addition, our results suggest that mtDNA haplogroups and some sensitive sites confer genetic susceptibility to ESCC and they can serve as potential biomarkers for clinical diagnosis.