Integrative molecular characterization of Chinese prostate cancer specimens / 亚洲男科学杂志(英文版)

Prostate cancer (PCa) exhibits epidemiological and molecular heterogeneity. Despite extensive studies of its phenotypic and genetic properties in Western populations, its molecular basis is not clear in Chinese patients. To determine critical molecular characteristics and explore correlations between genomic markers and clinical parameters in Chinese populations, we applied an integrative genetic/transcriptomic assay that combines targeted next-generation sequencing and quantitative real-time PCR (qRT-PCR) on samples from 46 Chinese patients with PCa. Lysine (K)-specific methyltransferase 2D (KMT2D), zinc finger homeobox 3 (ZFHX3), A-kinase anchoring protein 9 (AKAP9), and GLI family zinc finger 1 (GLI1) were frequently mutated in our cohort. Moreover, a clinicopathological analysis showed that RB transcriptional corepressor 1 (RB1) deletion was common in patients with a high risk of disease progression. Remarkably, four genomic events, MYC proto-oncogene (MYC) amplification, RB1 deletion, APC regulator of WNT signaling pathway (APC) mutation or deletion, and cyclin-dependent kinase 12 (CDK12) mutation, were correlated with poor disease-free survival. In addition, a close link between KMT2D expression and the androgen receptor (AR) signaling pathway was observed both in our cohort and in The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) data. In summary, our results demonstrate the feasibility and benefits of integrative molecular characterization of PCa samples in disease pathology research and personalized medicine.

Changyanqing decoction produces anti-inflammatory effect by inhibiting the activation of nuclear factor-kappaB / 南方医科大学学报

<p><b>OBJECTIVE</b>To detect the changes in intestinal mucosal permeation in rats with methotrexate-induced small intestinal damage and investigate the protective effects of Changyanqing decoction.</p><p><b>METHODS</b>Rat enteritis model was established by methotrexate (MTX) and sodium chloride. The rats were randomly divided into normal control group, model group, N-acetylcysteine (NAC) group and Changyanqing decoction group, and Changyanqing decoction (100 mg/kg) or saline was administered daily in the corresponding groups by gastric irrigation for 6 days. The disease activity index (DAI), colonic mucosal damage index (CMDI) and histological score (HS) of the rats were observed and evaluated. The levels of mRNA expressions of TNF-alpha and IL-1beta were detected by semi-quantitative RT-PCR. The expression of IL-10 was detected by enzyme linked immunosorbent assay, and IkappaB expression was determined with Western blotting.</p><p><b>RESULTS</b>Compared with the normal control group, the model group showed significantly increased DAI, CMDI and HS. The DAI, CMDI, and HS in rats treated with Changyanqing decoction were significantly decreased in comparison with those in the model group (P<0.01). The expressions of TNF-alpha and IL-1beta were significantly higher in MTX-treated group than in the control group. The expression of TNF-alpha and IL-1beta mRNA in the Changyanqing group and NAC group were significantly lower, but IL-10 significantly higher than those of the MTX group. In MTX group, obvious NF-kappaB activation was observed, whose expression was significantly stronger in the cell nuclei, and the IkappaB in the cytoplasm was markedly degraded.</p><p><b>CONCLUSION</b>Changyanqing decoction offers protection on intestinal mucosa by inhibiting NF-kappaB activation to reduce TNF-alpha and IL-1beta mRNA expressions and increase IL-10 expression.</p>

Value of prostate specific antigen in early diagnosis of prostatic cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the value of serum prostate specific antigen (PSA), free PSA (FPSA) and PSA density (PSAD) in early diagnosis of prostatic cancer.</p><p><b>METHODS</b>Sixty-eight patients with benign prostate hyperplasia (BPH), 28 with prostatic intraepithelial neoplasia (PIN) without canceration, and 32 with prostatic cancer, all diagnosed by prostatic biopsy, were enrolled in this study. Serum PSA and FPSA were measured and FPSA/PSA ratio and PSAD calculated for each patient, and the data analyzed to explore the association of these indices with prostatic cancer.</p><p><b>RESULTS</b>Serum PSA level and PSAD were markedly different between the cancer patients and non-cancer patients (P<0.001 and P<0.01, respectively). FPSA/PSA ratio also differed between them (P<0.05). The same results were also found between BPH and cancer patients. Significant difference was noted in serum PSA and PSAD between PIN and cancer patients (P<0.01), but not in FPSA/PSA ratio (P>0.05). No marked difference was observed in serum PSA, FPSA/PSA ratio and PSAD between BPH and PIN patients.</p><p><b>CONCLUSION</b>Serum PSA provides a very important clue for early diagnosis of prostatic cancer, and more accurate diagnosis can be obtained by considering also FPSA/PSA ratio. PSAD may also assist in the early diagnosis of prostatic cancer.</p>

Frequencies of CGT52TGT, GGC54GAC and GGA57GAA point mutations in MBL gene in Chinese Uyghur population / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the frequencies of three point mutations, CGT52TGT, GGC54GAC and GGA57GAA, in exon 1 of mannan-binding lectin (MBL) structural gene in Chinese Uyghur population.</p><p><b>METHODS</b>Blood samples were collected from a Uyghur population in Xinjiang Uyghur Autonomous Region, and the genomic DNA was extracted from the leucocytes and the target gene fragment amplified by PCR. The three point mutations in exon 1 of MBL gene were detected by fluorogenic probe hybridization technique with visual monitoring.</p><p><b>RESULTS</b>In 95 Uyghur individuals, 2 were identified as homozygous for codon 54 mutations, 28 were heterozygous for codon 54 mutation, and no CGT52TGT and GGA57GAA point mutations were found.</p><p><b>CONCLUSION</b>The frequencies of CGT52TGT, GGC54GAC and GGA57GAA mutant alleles in exon 1 of MBL structural gene are 0, 0.168 and 0 respectively in the Chinese Uyghur population.</p>

Investigation of single nucleotide polymorphisms, haplotypes and genotypes of mannan-binding lectin gene in Bai(Pai) nationality in China / 中国免疫学杂志

Objective:To investigate the single nucleotide polymorphisms(SNP), haplotypes and genotypes of mannan-binding lectin(MBL) gene in the Bai(Pai) nationality from YunNan province, China.Methods:The three SNP sites CGT52TGT, GGC54GAC and GGA57GAA(named alleles D, B and C respectively, wildtype named A) in exon1 of MBL gene of 70 DNA samples of Bai nationality whose three SNP sites, -550G/C, -221C/G and +4C/T(named alleles H/L, X/Y and P/Q respectively), in promoter region of MBL gene had been clear, haplotypes and genotypes of MBL genes were detected and analyzed by sequence specific primer-polymerase chain reaction.Results:It was found that in Bais population, the frequency of alleles B was 0.100, there only were five haplotypes, HYPA, LXPA, LYQA, LYPA and LYPB, whose frequencies were 0.250, 0.107, 0.407, 0.135 and 0.100 respectively, the frequencies of several genotypes were LYPA/LYPA 0.043, LXPA/LYQA 0.143, LYPA/LYPB 0.014, HYPA/LYQA 0.086, LYPA/ LYQA 0.157, HYPA/LYPA 0.014, LYPB/LYQA 0.143, HYPA/LYPB 0.043, LXPA/LXPA 0.014, HYPA/LXPA 0.043, LYQA/LYQA 0.143 and HYPA/HYPA 0.157.Conclusion:In the MBL genes in Bais population, there is the allele B, the polymorphism haplotypes are mostly LYQA and HYPA, and the genotypes, LYPA/LYQA, HYPA/HYPA, LXPA/LYQA, LYPB/LYQA and LYQA/LYQA.