A risk model based on 10 ferroptosis regulators and markers established by LASSO-regularized linear Cox regression has a good prognostic value for ovarian cancer patients.

Ovarian cancer is the deadliest gynecologic cancer due to its high rate of recurrence and limited early diagnosis. For certain patients, particularly those with recurring disorders, standard treatment alone is insufficient in the majority of cases. Ferroptosis, an iron- and ROS (reactive oxygen species)-reliant cell death, plays a vital role in the occurrence of ovarian cancer. Herein, subjects from TCGA-OV were calculated for immune scores using the ESTIMATE algorithm and assigned into high- (N = 185) or low-immune (N = 193) score groups; 259 ferroptosis regulators and markers were analyzed for expression, and 64 were significantly differentially expressed between two groups. These 64 differentially expressed genes were applied for LASSO-regularized linear Cox regression for establishing ferroptosis regulators and a markers-based risk model, and a 10-gene signature was established. The ROC curve indicated that the risk score-based curve showed satisfactory predictive efficiency. Univariate and multivariate Cox risk regression analyses showed that age and risk score were risk factors for ovarian cancer patients' overall survival; patients in the high-risk score group obtained lower immune scores. The Nomogram analysis indicated that the model has a good prognostic performance. GO functional enrichment annotation confirmed again the involvement of these 10 genes in ferroptosis and immune activities. TIMER online analysis showed that risk factors and immune cells were significantly correlated. In conclusion, the risk model based on 10 ferroptosis regulators and markers has a good prognostic value for ovarian cancer patients.

lncRNA AC005224.4/miR-140-3p/SNAI2 regulating axis facilitates the invasion and metastasis of ovarian cancer through epithelial-mesenchymal transition.

BACKGROUND: Ovarian cancer is one of the most widespread malignant diseases of the female reproductive system worldwide. The plurality of ovarian cancer is diagnosed with metastasis in the abdominal cavity. Epithelial-mesenchymal transition (EMT) exerts a vital role in tumor cell metastasis. However, it remains unclear whether long non-coding RNA (lncRNA) are implicated in EMT and influence ovarian cancer cell invasion and metastasis. This study was designed to investigate the impacts of lncRNA AC005224.4 on ovarian cancer. METHODS: LncRNA AC005224.4, miR-140-3p, and snail family transcriptional repressor 2 ( SNAI2 ) expression levels in ovarian cancer and normal ovarian tissues were determined using real-time quantitative polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8) and Transwell (migration and invasion) assays were conducted to measure SKOV3 and CAOV-3 cell proliferation and metastasis. E-cadherin, N-cadherin, Snail, and Vimentin contents were detected using Western blot. Nude mouse xenograft assay was utilized to validate AC005224.4 effects in vivo . Dual-luciferase reporter gene assay confirmed the targeted relationship between miR-140-3p and AC005224.4 or SNAI2 . RESULTS: AC005224.4 and SNAI2 upregulation and miR-140-3p downregulation were observed in ovarian cancer tissues and cells. Silencing of AC005224.4 observably moderated SKOV3 and CAOV-3 cell proliferation, migration, invasion, and EMT process in vitro and impaired the tumorigenesis in vivo . miR-140-3p was a target of AC005224.4 and its reduced expression level was mediated by AC005224.4. miR-140-3p mimics decreased the proliferation, migration, and invasion of ovarian cancer cells. SNAI2 was identified as a novel target of miR-140-3p and its expression level was promoted by either AC005224.4 overexpression or miR-140-3p knockdown. Overexpression of SNAI2 also facilitated ovarian cancer cell viability and metastasis. CONCLUSION: AC005224.4 was confirmed as an oncogene via sponging miR-140-3p and promoted SNAI2 expression, contributing to better understanding of ovarian cancer pathogenesis and shedding light on exploiting the novel lncRNA-directed therapy against ovarian cancer.

Adjuvant chemotherapy versus adjuvant concurrent chemoradiotherapy after radical surgery for early-stage cervical cancer: a randomized, non-inferiority, multicenter trial.

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.

MicroRNA-665 promotes the proliferation of ovarian cancer cells by targeting SRCIN1.

Recent studies have discovered several microRNAs (miRNAs/miRs) as biomarkers for the prediction of ovarian cancer by detecting miRNA profiles in serum samples from healthy volunteers and patients with ovarian cancer. However, whether and how these miRNAs are involved in tumorigenesis is not known. In the present study, the expression of miR-665, a recently discovered biomarker for ovarian cancer, was upregulated in tumor tissues from patients with ovarian cancer compared with normal tissues. Inhibition of miR-665 inhibited cell proliferation ability and inactivated MAPK/ERK signaling of ovarian cancer cells. Using bioinformatics analysis, Src kinase signaling inhibitor 1 (SRCIN1) was predicted as a potential target gene of miR-665. Reverse transcription-quantitative PCR and western blotting showed that SRCIN1 expression was repressed by miR-665 in ovarian cancer cells. In addition, a dual luciferase activity assay showed that SRCIN1 was a target gene of miR-665. Silencing of SRCIN1 could reverse the cell growth arrest, which was induced by the miR-665 inhibitor. Moreover, miR-665 levels were negatively correlated with SRCIN1 mRNA levels in tumor tissues from patients with ovarian cancer. In conclusion, the present data suggested that miR-665 functioned as an oncogene in ovarian cancer by directly repressing the expression of SRCIN1.

Clinical significance of melanoma cell adhesion molecule CD146 and VEGFA expression in epithelial ovarian cancer.

Ovarian cancer is the fifth most common type of cancer in females; however, its asymptomatic progression and the lack of an efficient screening strategy leads to late diagnosis. The present study aimed to investigate the expression levels of cluster of differentiation (CD)146 and vascular endothelial growth factor A (VEGFA) in epithelial ovarian cancer, and their clinical significance. A total of 52 ovarian samples were tested, of which 22 were from patients with epithelial ovarian cancer and 30 were from non-cancer patients. The relative gene expression of CD146 and VEGFA was quantified using reverse transcription-quantitative polymerase chain reaction analysis. Western blotting was used to determine the protein expression levels. The relative gene expression levels of CD146 and VEGFA in tumor tissues were significantly increased compared with the control (4.92±0.44 vs. 1.05±0.06 and 3.08±0.17 vs. 1.06±0.07, P<0.01). The protein expression levels of CD146 and VEGFA in tumor tissue were also significantly increased compared with the control (0.70±0.02 vs. 0.41±0.07 and 0.54±0.01 vs. 0.26±0.01, P<0.01). There was a positive correlation between the expression levels of CD146 and VEGFA genes (r=0.78) and between the two proteins (r=0.69). Dot density frequency analysis indicated that CD146 and VEGFA were specifically present in tumor tissues. In conclusion, CD146 and VEGFA are co-overexpressed in ovarian cancer; their potential as tumor biomarkers or therapeutic targets for the treatment of ovarian cancer requires further investigation.

The peripheral blood neutrophil-to-lymphocyte ratio is a prognostic predictor for survival of EGFR-mutant nonsmall cell lung cancer patients treated with EGFR-TKIs.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the standard first-line treatment for EGFR-mutant nonsmall cell lung cancer (NSCLC) patients. However, studies have reported that not all NSCLC patients harboring kinase domain mutations in epidermal growth factor receptor (EGFR) show significant clinical benefits from EGFR-targeted tyrosine kinase inhibitors (TKIs). Therefore, it is necessary to establish feasible biomarkers to predict the prognosis of EGFR-mutant NSCLC patients treated with EGFR-TKIs. This study aimed to determine biomarkers using inflammatory parameters from complete blood counts to predict the prognosis of EGFR-mutant NSCLC patients treated with EGFR-TKIs.We retrospectively investigated 127 stage IIIB/IV NSCLC patients with activating EGFR mutations who were treated with EGFR-TKIs. We used receiver operating characteristic (ROC) curves to determine the optimal cut-off for the inflammatory markers as prognostic factors. Additionally, univariate and multivariate analyses were used to identify prognostic factors for progression-free survival (PFS) and overall survival (OS) of EGFR-mutant NSCLC patients treated with EGFR-TKIs.The receiver operating characteristic analysis indicated that the lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) cut-off values were 3.37 and 2.90, respectively. The univariate analysis showed that a high LMR (>3.37) and low NLR (≤2.90) were significantly correlated with long-term PFS and OS (LMR, P = .007; NLR, P < .001). The multivariate Cox regression analysis revealed that only low NLR was an independent prognostic factor for long-term PFS and OS (PFS, HR = 0.573, 95% CI: 0.340-0.964, P = .036; OS, HR = 0.491, 95% CI: 0.262-0.920, P = .026).The data show that a low NLR was a good prognostic factor in EGFR-mutant NSCLC patients receiving EGFR-TKIs treatment. Moreover, the NLR measurement has better prognostic value than LMR.