Protein-coding genes, long non-coding RNAs combined with microRNAs as a novel clinical multi-dimension transcriptome signature to predict prognosis in ovarian cancer.

Ovarian cancer is prevalent in women which is usually diagnosed at an advanced stage with a high mortality rate. The aim of this study is to investigate protein-coding gene, long non-coding RNA, and microRNA associated with the prognosis of patients with ovarian serous carcinoma by mining data from TCGA (The Cancer Genome Atlas) public database. The clinical data of ovarian serous carcinoma patients was downloaded from TCGA database in September, 2016. The mean age and survival time of 407 patients with ovarian serous carcinoma were 59.71 ± 11.54 years and 32.98 ± 26.66 months. Cox's proportional hazards regression analysis was conducted to analyze genes that were significantly associated with the survival of ovarian serous carcinoma patients in the training group. Using the random survival forest algorithm, Kaplan-Meier and ROC analysis, we kept prognostic genes to construct the multi-dimensional transcriptome signature with max area under ROC curve (AUC) (0.69 in the training group and 0.62 in the test group). The selected signature composed by VAT1L, CALR, LINC01456, RP11-484L8.1, MIR196A1 and MIR148A, separated the training group patients into high-risk or low-risk subgroup with significantly different survival time (median survival: 35.3 months vs. 64.9 months, P < 0.001). The signature was validated in the test group showing similar prognostic values (median survival: 41.6 months in high-risk vs. 57.4 months in low-risk group, P=0.018). Chi-square test and multivariable Cox regression analysis showed that the signature was an independent prognostic factor for patients with ovarian serous carcinoma. Finally, we validated the expression of the genes experimentally.

Inhibitory effects of an antisense PCDGF vector on proliferation and invasion of highly malignant ovarian cancer cells and the related mechanism / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the inhibitory effects of an antisense PC cell derived growth factor (PCDGF) vector on proliferation and invasion of highly malignant ovarian cancer cell lines Sw626 and A2780 cells, and preliminarily explore the related mechanisms.</p><p><b>METHODS</b>MTT assay and Boyden chamber in vitro invasion assay were employed to detect the changes of proliferation and invasion ability in the Sw626 and A2780 cells transfected with anti-sense PCDGF. The expression levels of cyclin D1 and CDK4 proteins before and after transfection were detected by Western blotting. The effects on the expression and activity of MMP-2 were evaluated by quantitative RT-PCR and zymography, respectively.</p><p><b>RESULTS</b>Comparing with the blank group, the proliferation inhibition rate of the Sw626 and A2780 cells transfected with anti-sense PCDGF was 72.9% and 70.9%, respectively, and the invasion ability was inhibited by 62.9% and 59.0%, respectively. The levels of cyclin D1 and CDK4 protein expression in antisense PCDGF transfected cells were 0.38 +/- 0.08 and 0.37 +/- 0.13, respectively, all significantly lower than 0.84 +/- 0.11 and 0.64 +/- 0.11, respectively, in the blank group (P < 0.01). The MMP-2 mRNA expression level in antisense PCDGF transfected cell group was 0.66 +/- 0.11, not significantly decreased in comparison with 0.89 +/- 0.09 in the blank group (P > 0.05), but the activity of MMP-2 was inhibited significantly.</p><p><b>CONCLUSION</b>The antisense PCDGF vector may inhibit markedly the proliferation and invasion of highly malignant ovarian cancer cells, and partially reverses their malignant phenotype. It seems to be related with down-regulating the expression of cyclin D1 and CDK4 and inhibiting the activity of MMP-2. Our findings indicate that PCDGF may become a new target for antisense gene therapy of ovarian cancer.</p>

Microsatellite instability and loss of heterozygosity of human leucocyte antigen class I gene in cervical carcinoma / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the frequency of microsatellite instability (MSI) and loss of heterozygosity (LOH) at human leucocyte antigen(HLA) class I loci in cervical carcinoma and the detailed deletion mapping in this region.</p><p><b>METHODS</b>LOH and MSI of HLA class I genes were analyzed in 30 paired blood and tumor samples by PCR based single-stranded length polymorphism (PCR-SSLP).</p><p><b>RESULTS</b>Of the 30 cases, 23(76.7%) showed LOH at one or more loci. Higher frequencies of LOH were found at four loci: C3_2_11 (50%), C1_4_4 (37%), C1_2_5 (36.7%), D6S276 (48.3%). MSI was found in 20 out of 30 cases (66.7%).</p><p><b>CONCLUSION</b>The data suggest that the LOH and MSI of HLA class I gene might participate in the carcinogenesis of cervical carcinoma. Meanwhile, the minimal deletion region might be defined between C1_2_5 and C3_2_11, thus providing the evidence for cloning the tumor suppressor genes associated with cervical carcinoma.</p>