[Bioinformatics study of sperm proteomics in oligoasthenozoospermia].

OBJECTIVE: To identify differentially expressed proteins in the sperm of oligoasthenozoospermia (OAZ) patients and provide some theoretical evidence for the study of OAZ. METHODS: We collected semen samples from 30 OAZ patients and another 30 normal healthy males. Using the tandem mass tag (TMT) and proteomic technology, we identified differentially expressed proteins in the sperm of the OAZ patients and normal subjects, followed by gene ontology (GO) analysis and bioinformatics analysis of the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways. RESULTS: A total of 1 199 differentially expressed sperm proteins were obtained from the semen samples of the subjects by proteomic technology, of which 663 were up-regulated and 536 down-regulated. GO analysis preliminarily indicated that the differential proteins played a leading role in the composition and function of the ribosome, while KEGG pathway analysis showed that the differential proteins were involved in 244 signaling pathways. CONCLUSIONS: Differentially expressed proteins in the sperm of OAZ patients involve complex biological processes, molecular functions and signaling pathways, and proteomic screening and bioinformatics analysis are helpful for the study of the pathogenesis of oligoasthenozoospermia.

[Differentially expressed proteins in the penile tissue of rats with compound stress-induced ED after intervention with Yimusake Tablets: A bioinformatics analysis].

OBJECTIVE: To search for specific protein makers and target proteins for intervention with Yimusake Tablets (YT) in the penile tissue of rats with ED induced by compound cold stress and explore the molecular mechanisms underlying the development and progression of ED. METHODS: Eighty adult male rats were screened and divided into three groups, normal control (n = 10), ED model control (n = 15) and YT intervention (n = 15). The model of compound cold stress-induced ED was established in the latter two groups, and meanwhile the animals in the YT intervention group were treated with oral YT for 2 weeks. After that, proteins were extracted from the penile tissues of the rats for screening and identification by iTRAQ labeling combined with LC-MS-MS proteomics, and the IPA bioinformatics software was used for analysis of differentially expressed proteins. RESULTS: A total of 48 differentially expressed proteins were identified from the penile tissue of the ED model controls, of which 18 were associated with endothelial function, 5 with smooth muscle activity and 4 with inflammation, involving the biological processes of glucose metabolism and alcohol catabolism and the signaling pathways of glucose metabolism, calcium and RXR activation. In comparison, 29 differentially expressed proteins were identified from the rats in the YT intervention group, of which 5 were associated with endothelial function, 1 with smooth muscle activity and 4 with inflammation, involving the biological processes of glucose metabolism, vasodilation and acute-phase response and the signaling pathways glucose metabolism, RXR activation and acute-phase response. Seven ED-associated candidate biomarkers were obtained from the differentially expressed proteins in the ED model control and YT intervention group, including Collagen alpha-1(III) chain（COL3α1）, Collagen alpha-1(I) chain（COL1α1）, Collagen alpha-2(I) chain（COL1α2）, Glyceraldehyde-3-phosphate dehydrogenase（GAPDH）, T-kininogen 1（MAP1）,Biglycan（BGN）, and Myosin-11（MYH11）. CONCLUSIONS: Changes of vascular endothelial and smooth muscle functions in the penile tissue are likely to be the key mechanisms underlying the development and progression of compound stress-induced ED, which is also associated with inflammation as well as the interaction of the identified differentially expressed proteins and their participation in the relevant signaling pathways. The 7 proteins obtained can be used as the markers of compound stress-induced ED in the rat penile tissue, of which MAP1, GAPDH, BGN and MYH11 may serve as target proteins for YT intervention.

Upregulation of protein tyrosine phosphatase type IVA member 3 (PTP4A3/PRL-3) is associated with tumor differentiation and a poor prognosis in human hepatocellular carcinoma.

BACKGROUND: Protein tyrosine phosphatase type IVA member 3 (PTP4A3/PRL-3), a metastasis-associated phosphatase, plays multiple roles in cancer metastasis. We investigated PTP4A3/PRL-3 expression and its correlation with the clinicopathological features and prognosis in hepatocellular carcinoma (HCC). METHODS: Gene expression profiles of PTP4A3/PRL-3 were obtained in poorly differentiated HCC tissues. The results were validated independently by TaqMan gene expression assays and immunohistochemical analysis. RESULTS: According to the microarray profiles, PTP4A3/PRL-3 was upregulated in patients with poorly differentiated disease compared to patients with well-differentiated disease with hepatic backgrounds associated with hepatitis B or C. Validation analysis showed that the PTP4A3/PRL-3 mRNA and protein levels were significantly associated with poor differentiation (P<0.0001), high serum α-fetoprotein (P<0.01), high serum protein induced by vitamin K absence/antagonist-II (PIVKA-II), and hepatic vascular invasion (P<0.05). The expression of PTP4A3/PRL-3 protein was also correlated with advanced cancer stages (P<0.01); this resulted in a significantly poorer prognosis in both overall (P=0.0024) and recurrence-free survival (P=0.0227). According Cox regression univariate analysis, the positive expression of PTP4A3/PRL-3 was a poor risk prognostic factor (OS, P=0.0031; recurrence-free survival, P=0.0245). Cox regression multivariate analysis indicated that high PTP4A3/PRL-3 expression was an independent, unfavorable prognostic factor for overall survival (hazard ratio 0.542; P=0.048). CONCLUSIONS: PTP4A3/PRL-3 might be closely associated with HCC progression, invasion, and metastasis. Its high expression had a negative impact on the prognosis of HCC patients. This strongly suggests that PTP4A3/PRL-3 should be considered as a prognostic factor. Further analysis should be pursued to evaluate it as a novel prognostic target.

Villin 1 is a predictive factor for the recurrence of high serum alpha-fetoprotein-associated hepatocellular carcinoma after hepatectomy.

The prognostic assessment of patients with hepatocellular carcinoma (HCC) after resection is an important clinical issue. The present study investigated those genes associated with high serum alpha-fetoprotein (AFP), and their clinical significance, including prognosis and recurrence after hepatectomy. Based on gene expression analysis of 110 training HCC cases, 20 genes whose mRNA expression levels were significantly upregulated and 50 genes that were downregulated correlated with high serum AFP-associated HCC patients. Gene expression profiles of Villin1 (Vil1) were obtained in high serum AFP-associated HCC tumor tissues. In the present analysis, only VIL1 was significantly correlated with the recurrence of HCC. The results were validated independently using Taqman gene expression assays and immunostaining analysis. Results showed that the upregulation of VIL1 mRNA was also correlated with high serum PIVKAII, vascular invasion (P < 0.05), poor differentiation, an advanced cancer stage (P < 0.01) and recurrence-free survival (P = 0.017). The upregulation of VIL1 mRNA was observed more frequently in the early recurrence patients as compared to the late recurrence patients. Cox regression univariate and multivariate analyses indicated that high serum AFP levels (overall survival, HR 1.675, P = 0.002; FRS, HR 1.359, P = 0.039) and Vil1 protein expression (overall survival, HR 0.253, P = 0.009; FRS, HR 0.401, P = 0.041) were independent, unfavorable prognostic factors for overall and recurrence-free survival of patients. We demonstrated that the VIL1 gene is a potential candidate molecular marker for high serum AFP-associated HCC and a predictive candidate for the postoperative recurrence and poorer prognosis of HCC.