Development and validation of a nomogram for predicting specific mortality risk: A study of competing risk model based on real endometrial cancer patients.

OBJECTIVE: This study aimed to construct a competing risk prediction model for predicting specific mortality risks in endometrial cancer patients from the SEER database based on their demographic characteristics and tumor information. METHODS: We collected relevant clinical data on patients with histologically confirmed endometrial cancer in the SEER database between 2010 and 2015. Univariate and multivariate competing risk models were used to analyze the risk factors for endometrial cancer-specific death, and a predictive nomogram was constructed. C-index and receiver operating characteristic curve (ROC) at different time points were used to verify the accuracy of the constructed nomogram. RESULTS: There were 26 109 eligible endometrial cancer patients in the training cohort and 11 189 in the validation cohort. Univariate and multivariate analyses revealed that Age, Marriage, Grade, Behav, FIGO, Size, Surgery, SurgOth, Radiation, ParaAortic_Nodes, Peritonea, N positive, DX_liver, and DX_lung were independent prognostic factors for specific mortality in endometrial cancer patients. Based on these factors, a nomogram was constructed. Internal validation showed that the nomogram had a good discriminative ability (C-index = 0.883 [95% confidence interval [CI]: 0.881-0.884]), and the 1-, 3-, and 5-year AUC values were 0.901, 0.886 and 0.874, respectively. External validation indicated similar results (C-index = 0.883 [95%CI: 0.882-0.883]), and the 1-, 3-, and 5- AUC values were 0.908, 0.885 and 0.870, respectively. CONCLUSION: We constructed a competing risk model to predict the specific mortality risk among endometrial cancer patients. This model has favorable accuracy and reliability and can provide a reference for the development and update of endometrial cancer prognostic risk assessment tools.

Clinical Diagnostic Values of C1q/TNF-Related Protein-3 for Polycystic Ovary Syndrome Women with Insulin Resistance.

Polycystic ovary syndrome (PCOS) is the most common disease caused by complex endocrine and metabolic abnormalities in women. Insulin resistance is considered an important pathophysiological factor in the pathogenesis of PCOS. Here we investigated the clinical values of C1q/TNF-related protein-3 (CTRP3) as predictive factor for insulin resistance. Our study included 200 patients with PCOS, among which 108 had insulin resistance. Serum CTRP3 levels were measured using enzyme-linked immunosorbent assay. Predictive values of CTRP3 for insulin resistance was analyzed using receiver operating characteristic (ROC) analysis. Correlations of CTRP3 to insulin levels, obesity measurements and blood lipid levels were determined using Spearman's correlation analysis. Our data suggested that PCOS patients with insulin resistance had a higher obesity, lower high-density lipoprotein cholesterol, higher total cholesterol, higher insulin levels and lower CTRP3 levels. CTRP3 had a high sensitivity (72.22%) and specificity (72.83%). CTRP3 significantly correlated to insulin levels, body mass index, waist-to-hip ratio, high-density lipoprotein, and total cholesterol levels. The predictive value of CTRP3 in PCOS patients with insulin resistance was supported by our data. Our findings suggest that CTRP3 is involved in the pathogenesis and insulin resistance of PCOS, which indicates its value as an indicator for the PCOS diagnosis.

Circ_0001247 functions as a miR-1270 sponge to accelerate cervical cancer progression by up-regulating ZEB2 expression level.

BACKGROUND: There is increasing evidence that circular RNA (circRNA) disorders have an impact on the progression of various malignancies. The expression characteristics, function and underlying mechanism of circ_0001247 in cervical cancer (CC) have not been confirmed. METHODS: GSE147483 datasets of circRNAs expression in CC cell line and normal cervical cell line were retrieved from GEO database, and the circRNA with significant difference was selected; circ_0001247, miR-1270, and Zinc finger E-box binding homeobox 2 (ZEB2) expressions in CC tissues and cell lines were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) assay; cell counting kit-8 (CCK-8) assay and BrdU assay were applied to monitor the proliferative ability of CC cells; Transwell assay was conducted to examine the migration and invasion of CC cells, and flow cytometry was used to evaluate the apoptosis; Western blot assay was adopted to detect ZEB2 protein expressions; dual-luciferase report gene assay was used to verify the targeting relationship between circ_0001247 and miR-1270, and miR-1270 and the 3'UTR of ZEB2. RESULTS: Analysis of GSE147483 suggested that circ_0001247 could probably be an oncogenic circRNA in CC. Compared with that in adjacent tissues and normal cervical epithelial cells, circ_0001247 expression in CC tissues and cell lines was significantly increased; knocking down circ_0001247 expression could inhibit the proliferation and metastasis of CC cells, and promote apoptosis, while circ_0001247 overexpression worked oppositely; circ_0001247 sponged miR-1270 in CC cells; miR-1270 diminished the promoting effect of circ_0001247 by inactivating the ZEB2. CONCLUSION: Circ_0001247 promotes progression of CC by sponging miR-1270 to upregulate ZEB2 expression level.

Long non-coding RNAs involved in gynecological cancer.

Long non-coding RNAs (lncRNAs) are defined as transcripts longer than 200 nucleotides with little or no protein-coding capacity. Previously, they were considered transcription byproducts without biological functions. Further studies have shown that lncRNAs are involved in multiple biological and pathological processes, including regulation of epigenetic, transcriptional, and posttranscriptional events. Long non-coding RNA expression patterns in various malignant tumors differ from those of benign tumors and normal tissue, and such alterations may promote or suppress tumorigenesis and cancer progression. The expression profiles of lncRNAs are abnormal in gynecological cancers, such as ovarian cancer, cervical cancer, and endometrial cancer, suggesting an important role for lncRNAs in tumorigenesis/progression of these cancers. Here, we summarized the research progress on identifying the biological functions of lncRNAs in tumorigenesis, progression, and metastasis in gynecological cancers. We provide references for exploring the clinical applications of lncRNAs as early diagnostic biomarkers or ideal therapeutic targets in gynecological cancers.

Circular RNA circ_0011385 promotes cervical cancer progression through competitively binding to miR-149-5p and up-regulating SOX4 expression.

Circular RNAs (circRNAs), emerging as a new type of non-coding RNAs, play important roles in cancers. Instead, the functions and mechanisms of circ_0011385 in cervical cancer (CC) are still inconclusive. Microarray data GSE102686 was downloaded from Gene Expression Omnibus (GEO) database, and were utilized to screen out circRNAs differently expressed in CC tissues. Circ_0011385, miR-149-5p, SRY-box transcription factor 4 (SOX4) mRNA expressions in CC tissues and cells were probed by quantitative real-time PCR (qRT-PCR). CC cell lines with circ_0011385 knockdown were constructed, and he multiplication, migration, invasion, and apoptosis of CC cells were evaluated by cell counting kit-8 (CCK-8) method, transwell assay, and flow cytometry. In addition, the targeting relationships between miR-149-5p and circ_0011385 or SOX4 mRNA 3'UTR were probed by dual-luciferase reporter gene assay and RNA pull-down assay. The regulatory function of circ_0011385 and miR-149-5p on SOX4 expression was studied with western blot. Expressions of circ_0011385 and SOX4 mRNA were raised in CC tissues and cells, while miR-149-5p expression was decreased. Knocking down circ_0011385 restrained the multiplication, migration, and invasion of CC cells and induced the apoptosis. Circ_0011385 directly targeted miR-149-5p, and SOX4 was the target of miR-149-5p, which could be positively regulated by circ_0011385. Circ_0011385 elevates SOX4 expression by targeting miR-149-5p, thus participating in promoting the malignant biological behaviors of CC cells.

Aberrant expression of pim-3 promotes proliferation and migration of ovarian cancer cells.

Pim kinase-3(Pim-3), a member of serine/threonine protein kinases, has been implicated in multiple human cancers and involved in Myc-induced tumorigenesis. However, little is known regarding its expression and biological function in human ovarian cancer. In this study we showed that the clinical significance and biological functions of Pim-3 in ovarian cancer and found that higher Pim-3 mRNA level are detected in ovarian cancer tissues than those in normal ovarian tissues. There are significant correlations between higher Pim-3 expression levels with the FIGO stage, histopathological subtypes, and distant metastasis in ovarian cancer patients. Lentivirus-mediated gene overexpression of Pim-3 significantly promotes the proliferation and migration of SKOV3 cell lines. Furthermore, MACC1 and Pim-3 expression were significantly correlated in human ovarian cancer cells, and overexpression of Pim-3 in ovary cancer cells increased MACC1 mRNA and protein expression. The data indicate that Pim-3 acts as a putative oncogene in ovary cancer and could be a viable diagnostic and therapeutic target for ovarian cancer.