Circulating Insulin-Like Growth Factor-1 Level and Ovarian Cancer Risk

Zhang

et al. 2017

Cell Physiol Biochem

Background/Aims: Ovarian cancer is often diagnosed at later stages with poor prognosis. Recent studies have associated the expression of deubiquitylase USP7 with the survival of ovarian cancers. Being a cysteine protease, USP7 could become a target for pharmacological intervention. Therefore, in this study, we assessed the influence of its inhibitor P5091 on ovarian cancer cells. Methods: Ovarian cancer cells were treated with P5091, and cell proliferation was measured with MTT assay; cell morphology was inspected under a phase-contrast microscope; cell cycle and cell death were examined by flow cytometry. To gain mechanistic insights into its effects, immunoblotting was performed to detect USP7, HDM2, p53, p21, apoptosis and autophagy related proteins. Results: P5091 effectively suppressed the growth of ovarian cancer cells, caused cell cycle blockage, and induced necrosis and apoptosis with more severe phenotypes observed in HeyA8 cells with wild-type p53 than in OVCAR-8 cells with mutant p53. P5091 also prompted autophagy, with more efficient p62 degradation in HeyA8. Conclusion: P5091 shows efficacy in suppressing ovarian cancers harbouring wild-type and mutant p53. Its effects seemed to be enhanced by wild-type p53. The potency of this USP7 inhibitor also correlated with autophagy to some extent. Therefore, the pharmacological targeting of USP7 may serve as a potential therapeutic strategy and warrants further investigation.

Section: Discussionmentioning

confidence: 99%

The USP7 Inhibitor P5091 Induces Cell Death in Ovarian Cancers with Different P53 Status

Zhang

et al. 2017

Cell Physiol Biochem

“…2,3 Moreover observational studies in non-acromegalic populations have reported that IGF-1 levels are positively associated with risk of colorectal, 4-6 prostate 5,7 and breast cancer, 5,8 but inversely with risk of ovarian cancer. 9 Data on circulating IGF-1 levels in relation to other cancers are limited and inconclusive. 1,5 Considering that circulating IGF-1 levels can be altered by diet (particularly by reduced milk and protein intake [10][11][12][13][14] and medical therapy, establishing the causal association between circulating IGF-1 levels and cancer risk are important from a public health and clinical perspective.…”

Section: Introductionmentioning

confidence: 99%

Insulin‐like growth factor‐1 and site‐specific cancers: A Mendelian randomization study

et al. 2020

Insulin‐like growth factor‐1 (IGF‐1) is involved in several processes relevant to carcinogenesis. We used 416 single‐nucleotide polymorphisms robustly associated with serum IGF‐1 levels to assess the potential causal associations between this hormone and site‐specific cancers through Mendelian randomization. Summary‐level genetic association estimates for prostate, breast, ovarian, and lung cancer were obtained from large‐scale consortia including individuals of European‐descent. Furthermore, we estimated genetic associations with 14 site‐specific cancers in European‐descent individuals in UK Biobank. Supplementary analyses were conducted for six site‐specific cancers using summary‐level data from the BioBank Japan Project. Genetically predicted serum IGF‐1 levels were associated with colorectal cancer. The odds ratio (OR) per standard deviation increase of IGF‐1 levels was 1.11 (95% confidence interval [CI] 1.01‐1.22; P = .03) in UK Biobank and 1.22 (95% CI 1.09‐1.36; P = 3.9 × 10−4) in the BioBank Japan Project. For prostate cancer, the corresponding OR was 1.10 (95% CI 1.01‐1.21; P = .04) in UK Biobank, 1.03 (95% CI 0.97‐1.09; P = .41) in the prostate cancer consortium, and 1.08 (95% CI 0.95‐1.22; P = .24) in the BioBank Japan Project. For breast cancer, the corresponding OR was 0.99 (95% CI 0.92‐1.07; P = .85) in UK Biobank and 1.08 (95% CI 1.02‐1.13; P = 4.4 × 10−3) in the Breast Cancer Association Consortium. There was no statistically significant association between genetically predicted IGF‐1 levels and 14 other cancers. This study found some support for a causal association between elevated serum IGF‐1 levels and increased risk of colorectal cancer. There was inconclusive or no evidence of a causal association of IGF‐1 levels with prostate, breast, and other cancers.

“…After primary therapy including debulking surgery and platinum-based adjuvant chemotherapy, approximately half of the patients will relapse within 1 year, and the five-year overall survival rate is less than 50% [3-5]. Therefore, effective bio-markers for individualized prediction of therapy outcomes and prognosis are urgently warranted.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Ovarian Cancer: A Systematic Review and Meta-Analysis of Observational Studies

Huang

Zhou

Zeng

et al. 2017

Cell Physiol Biochem

Background and Aims: Published data on the prognostic role of neutrophil-to-lymphocyte ratio (NLR) in ovarian cancer are controversial. We conducted this meta-analysis to obtain a more accurate assessment of prognostic significance of NLR in ovarian cancer. Materials and Methods: We conducted a systematic literature search using the electronic databases PubMed, Web of Science, and Embase up to May 2016. Hazard ratio (HR) and odd ratio (OR) with 95% confidence interval (95% CI) were calculated. Subgroup analyses were carried out to explore the source of heterogeneity. Statistical analysis was performed using Stata 10.0. Results: A total of 12 studies, consisting of 3,854 patients, which met our criterion were selected in this meta-analysis. Our pooled results showed that high pre-treatment NLR level was significantly associated with poorer overall survival (OS) (HR: 1.69, 95% CI 1.29-2.22) and shorter progression free survival (PFS) (HR 1.63, 95% CI 1.27–2.09). Additionally, increased NLR was also significantly correlated with advanced FIGO stage (OR 2.32, 95% CI1.79-3.00), higher serum level of CA-125 (OR 3.33, 95% CI 2.43-4.58), more extensive ascites (OR 3.54, 95% CI 2.31-5.42) as well as less chemotheraputic response (OR 0.53, 95% CI 0.40-0.70). The findings from most of subgroup meta-analyses were consistent with those from the overall meta-analyses. Conclusions: Elevated pre-treatment NLR could served as a predicative factor of poor prognosis for ovarian cancer patients.