AKT Isoforms Interplay in High-Grade Serous Ovarian Cancer Prognosis and Characterization

High-grade serous ovarian cancer (HGSOC) is among the deadliest gynecological malignancies. The acquired resistance to platinum-based therapies and the intrinsic heterogeneity of the disease contribute to the low survival rate. To improve patients’ outcomes, new combinatorial approaches able to target different tumor vulnerabilities and enhance the efficacy of the current therapies are required. AKT inhibitors are promising antineoplastic agents able to act in synergy with PARP inhibitors, but the spectrum of patients who can benefit from this combination is unclear, since the role of the three different isoforms of AKT is still unknown. Here, we study the expression of AKT isoforms on a retrospective cohort of archive tissue by RT-droplet digital PCR (ddPCR) analyzing their association with the clinicopathological features of patients. Based on AKT1/AKT2 and AKT1/AKT3 ratios, we define four AKT classes which were related to patients’ survival, tumor morphology and BRCA1 expression. Moreover, our results show that high AKT3 expression levels were frequently associated with tumors having classic features, a low number of mitoses and the presence of psammoma bodies. Overall, our study obtains new insights on AKT isoforms and their associations with the clinicopathological features of HGSOC patients. These evidences could help to better define the subsets of patients who can benefit from AKT and PARP inhibitors therapy in future clinical trials.

Pan-cancer Analysis Reveals the Small Nuclear Ribonucleoprotein Polypeptide C (SNRPC) Its Significance in Human Cancers

BackgroundSNRPC is cloned on human chromosome 6p21.31, which encodes a special protein component of U1 snRNP granules. Although SNRPC played an important role in the pre-mRNA splicing starting and adjustment, but in the tumor biological function is still unknown.MethodThrough the pan-cancer analysis of SNRPC, and our data sets, phosphorylation and functional network analysis based on TCGA (Cancer Genome Map) and GEO (Integrated Gene Expression Database), also from the western blot, qRT-PCR and CCK-8, cloning-forming experiment, scratch experiment to prove SNRPC biological function.ResultsSNRPC is related to the regulation of RNA, shear, and protease signals and has an important effect on ovarian cancer prognosis. Through a series of biological information data mining and basic experiments, we found that SNRPC plays an important role in the proliferation and migration of ovarian cancer. SNRPC expression is positively correlated with the immersion of CD4+T cells, macrophages, and neutrophils (p< 0.05), as obtained through the TIMER database (Tumor Immunological Assessment Resources) database. ConclusionOur pan-cancer research provides SNRPC in different tumors, especially the relatively comprehensive understanding of the carcinogenic potential of ovarian cancer.

Impact of Estrogen Receptor Expression on Prognosis of Ovarian Cancer According to Antibody Clone Used for Immunohistochemistry: A Meta-analysis

BackgroundThe prognostic value of the expression of estrogen receptor (ER) subtypes ER⍺ and ERβ in ovarian cancer has previously been evaluated by meta-analyses. However, the results are contradictory and controversial. MethodsWe conducted an updated meta-analysis with stringent inclusion criteria to ensure homogeneous studies to determine the effect of ER subtypes on ovarian cancer prognosis. Articles were retrieved by systematic search of PubMed and Web of Science for articles dated up to June 2021. Only studies with known hazard ratio (HR) and antibody clone for immunochemistry (IHC) were included. Pooled HRs with the corresponding 95% confidence intervals (CIs) were calculated for the effect of ER⍺ and ERβ expression on ovarian cancer patient progression-free survival (PFS) and overall survival (OS).ResultsA total of 17 studies were included, of which 11 and 13 studies examined the relationships between ER⍺ expression and PFS and OS, respectively, and 5 and 7 studies examined the relationships between ERβ expression and PFS and OS, respectively. Neither ER⍺ expression (random-effects model; HR=0.99, 95% CI=0.83-1.18) nor ERβ expression (fixed-effects model; HR=0.94, 95% CI=0.69-1.27) was associated with PFS. Random-effects models showed that ER⍺ expression (HR=0.81, 95% CI=0.64-1.02) and ERβ expression (HR=0.75, 95% CI=0.50-1.13) were only marginally and not significantly associated with better OS. Subgroup analysis revealed that ER⍺ expression determined using antibody clone 1D5 (HR=0.75, 95% CI=0.64-0.88) and ERβ expression determined using ERβ1-specific-antibody clone PPG5/10 or EMR02 (HR=0.65, 95% CI=0.50-0.86) were associated with significantly better OS, but ER expression determined using other antibodies was not.ConclusionsBoth ER⍺ expression and ERβ expression determined using certain antibody clones are significantly associated with OS of ovarian cancer patients, which suggests that both ER subtypes are prognostic biomarkers for ovarian cancer. The findings of this study provide new insight into the impact of ER expression on ovarian cancer prognosis.

1466Vitamin D status before, during and after treatment and ovarian cancer survival

Background Previous work found higher serum 25-hydroxyvitamin D (25(OH)D) [circulating form of vitamin D] concentrations at diagnosis were associated with longer survival in patients with ovarian cancer (OvCa). There was no evidence for an association with 25(OH)D after primary treatment, but power was limited. Our aim was to reassess this association in a larger sample, including measures collected during treatment and using techniques to deseasonalise 25(OH)D. Methods Participants were diagnosed between 2002-2006 and 2012-2015 from the Australian Ovarian Cancer Study (AOCS) and the Ovarian Cancer, Prognosis and Lifestyle (OPAL) study, respectively. 25(OH)D concentrations were available for 676 at diagnosis (AOCS), 805 during treatment (AOCS:208; OPAL:597) and 861 after completion of primary treatment and before recurrence (AOCS:342; OPAL:519); 1006 AOCS samples were included in the previous analysis. Sociodemographic, diet and lifestyle data came from questionnaires self-completed at recruitment, and clinical/survival data from medical records, supplemented with National Death Index linkage. We will use Cox regression and non-parametric models to examine associations with survival. Results Median 25(OH)D concentrations were lowest during treatment, intermediate at diagnosis and highest after treatment (AOCS 51, 64, and 71 nmol/L, respectively). 5-year survival was 50% in AOCS and 59% in OPAL. Updated survival results will be presented. Conclusions If the association is confirmed in this updated analysis, then increasing vitamin D concentrations may provide a way to improve survival following OvCa. Key messages Higher circulating vitamin D concentrations may improve survival in OvCa.

MCUR1 is a prognostic biomarker for ovarian cancer patients

PURPOSE: To propose MCUR1 gene as a potential biomarker for ovarian cancer prognosis. METHODS: The ovarian cancer patient specimen from TCGA database were analyzed using survival analysis. The immune cell infiltration ratio and checkpoints had also been investigated for different expression group of MCUR1. The function of MCUR1 as a ovarian cancer prognosis biomarker was verified in clinic. RESULTS: The low expression of MCUR1 was associated with the poor prognosis of ovarian cancer patients. The expressions of majority of immune cells and 6 checkpoints in low expression group of MCUR1 were significantly lower than that in high expression group of MCUR1 (P< 0.05). The MCUR1 could be utilized as a prognostic biomarker for ovarian cancer patients in clinic. CONCLUSION: This study has proposed a potential prognostic biomarker for ovarian cancer patients, which offers a beneficial reference for future ovarian cancer administration.

Platelets, Thrombocytosis, and Ovarian Cancer Prognosis: Surveying the Landscape of the Literature

Platelets are critical components of a number of physiologic processes, including tissue remodeling after injury, wound healing, and maintenance of vascular integrity. Increasing evidence suggests that platelets may also play important roles in cancer. In ovarian cancer, thrombocytosis, both at the time of initial diagnosis and at recurrence, has been associated with poorer prognosis. This review describes current evidence for associations between thrombocytosis and ovarian cancer prognosis and discusses the clinical relevance of platelet count thresholds and timing of assessment. In addition, we discuss several mechanisms from in vitro, in vivo, and clinical studies that may underlie these associations and recommend potential approaches for novel therapeutic targets for this lethal disease.