Background

The most common first symptom of ovarian cancer (OC) is the accumulation of serous fluid in the abdominal cavity. Morphological verification is necessary to resolve the issue of the nature of the process and the purpose of treatment. Cytological examination (CE) of ascitic fluid is a subjective method based on the knowledge and experience of a morphologist. The use of a comprehensive assessment of the CE with subsequent immunocytochemical (ICH) revision is a trend of modern diagnostics, and the use of test systems for the diagnosis of ICH, focused on one patient, will increase the availability of this type of study in the primary polyclinic. The aim of the work is to evaluate the diagnostic informativeness of using the SER 1 test system in the biochip format to determine the expression of EpCAM protein in ascitic fluid cells in the detection of OC.

Methods

70 samples of ascitic fluid obtained from patients with suspected OC who sought planned or emergency medical care at the surgical hospital of Nizhny Novgorod City Hospital No. 35 in 2021 were analyzed. All samples of ascitic fluid were examined cytologically. Using the SER1 test system (RUSSELL LLC, Russia), an ICH study was conducted, the results of which were visualized using a Zeiss Primo Star microscope (Carl Zeiss, Germany). The findings were classified in accordance with the International Cytological Classification of Effusion Fluids (TIS RSFC).

Results

During CE, data were obtained: non-diagnostic material (ND) - 11.4%, absence of malignant cells (NFM) - 44.3%, presence of cells with atypia of unclear significance (AUS) - 10%, suspicion of cancer (SFM) - 20%, malignant nature of cells (MAL) - 14.3%. An additional ICC study of EpCAM protein expression on SER 1 test systems changed the results within the categories: NFM - 58.6%, AUS - 0%, SFM - 2.8%, MAL - 27.2%.

Conclusions

A comprehensive assessment of the CE of effusion fluids, supplemented by ICH staining, increases the detectability of malignant tumor cells by 1.9 times, reducing the number of conclusions in the AUS,SFM categories. The use of the SER1 test system introduces ICH research into the practice of primary hospitals that do not belong to the oncology profile and contributes to the earlier diagnosis of OC.

Legal entity responsible for the study

The authors.

Funding

Russell Llc, Russian Federation.

Disclosure

All authors have declared no conflicts of interest.

Background

No residual disease after debulking surgery is the most critical independent prognostic factor for advanced ovarian cancer (AOC). There is an unmet clinical need for selecting primary or interval debulking surgery in AOC patients using existing prediction models such as CA-125, CT, PET-CT, or laparoscopy.

Methods

In this multiphase cohort study, 348 pre-treatment plasma and postsurgical tissue consecutive samples, and 272 patients were collected from four clinical centers. Circulating sEVs miRNAs profile associated with residual disease was revealed by RNA sequencing in AOC patients. MiRNAs expression was measured via TaqMan quantitative real-time PCR. The prediction model was established via the least absolute shrinkage and selection operator (LASSO), and logistic regression analysis based on the discovery-validation set. Plasma and tissue sEVs were captured by the magnetic bead sorting system (MACS) using cell-type-specific proteins as markers (EpCAM, FAP, CD45, CD235a, CD31).

Results

After analyzing a comprehensive plasma sEVs miRNAs profile in AOC, we identified and optimized a risk prediction model consisting of plasma sEVs-derived 4-miRNA (miR-320a-3p, miR-378a-3p, miR-1307-3p, let-7d-3p) and CA-125 (AUC:0.903; sensitivity:0.897; specificity:0.910; PPV:0.926; NPV:0.871). The quantitative evaluation of Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) suggested that the additional predictive power of the combined model was significantly improved contrasted with CA-125 or 4-miRNA alone (model vs CA-125, NRI=0.471, P<0.001; IDI=0.538, P<0.001; model vs 4-miRNA panel, NRI=0.122, P=0.001; IDI=0.185, P=0.003). Tumor cells-derived sEVs captured on EpCAM+ magnetic beads were the major vehicles affecting circulating sEVs 4-miRNA expressions. Moreover, the model index scores were significant differences between AOC and other confusable diseases (e.g., advanced colorectal cancer).

Conclusions

A reliable and stable model of circulating tumor-derived sEVs 4-miRNA plus CA-125 was established for preoperatively anticipating the high-risk AOC patients of residual disease to optimize clinical therapy.

Legal entity responsible for the study

J. Tang.

Funding

This work was supported by Grants from the General Project of Natural Science Foundation of Hunan Province (No. 2020JJ4051); Promotion Project of Health Suitability Program in Health Department of Hunan Province (No. WZ2020-15); Science and Technology Innovation Program of Hunan Province (No. 2020SK51101); Hunan Cancer Hospital Climbing Fund (No. ZX2020004); Capacity Building Project of Central Subsidy Medical and Health Institutions (No. 20201127-1001); Key Specialty Construction Project in Hunan Province (No. 20210826-1004); General Project in Health Department of Hunan Province (No. 202205015388).

Disclosure

The author has declared no conflicts of interest.

Background

The new ESGO-ESTRO-ESP 2020 risk classification system (molecular classification unknown) has allocated fewer patients to the high-risk group compared to the previous risk stratification system in 2016. The study aims to clinically validate the new system in predicting the outcome compared to the previous one.

Methods

We retrospectively analyzed the data of 684 patients treated between 2009 and 2013 for carcinoma endometrium in a tertiary care oncology center. The three years overall survival (OS) and disease-free survival (DFS) estimates were generated independently using the Kaplan Meier method for the new and previous classification system. Akaike information criterion and concordance index was calculated between both staging systems to identify better predictive model.

Results

After re-classification, 43% of patients in the high-risk group based on the 2016 system are shifted to the high-intermediate group and 93% of patients migrated from the high-intermediate to intermediate-risk group (Table). The 3-year OS for low risk, intermediate risk, high intermediate risk, high risk, and advanced patients according to the 2016 risk stratification system was 98.3%,95.7%,98%,90.1%, and 64.2% respectively and was 98.3%, 96.6%,92.9%,88.9% and 61.3% respectively according to the 2020 system. The 3-year DFS was 97.9%,79.3%,88.9%,77.3% and 57.2% according to the 2016 system and 97.9%,83%,85.3%,72.2% and 53.8% respectively with the 2020 system. The survival rate decreased from low to advanced risk groups and the newer high-risk group has a lower survival rate than the previous one. The Akaike Information Criterion was lower (0.685 versus 0.702) and Concordance Index values were better (1566.661 versus1545.505) for ESGO 2020 system for DFS, indicating that the newer edition gives a better predictive model Table: 22P

ESGO 2016 and ESGO-2020 cross-tabulation

Conclusions

The new 2020 risk stratification appears better predictive of survival events.

Legal entity responsible for the study

Institutional Review Board, Regional Cancer Centre, Thiruvananthapuram.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Recent studies have indicated that N6-methyladenosine (m6A) methylation modification and regulators play a critical role in human cancers. However, the possible functions of m6A and its regulators on cervical cancer (CC) tumorigenesis are still unclear. This study explored the function and mechanism of METTL3 (methyltransferase-like 3) and its downstream target oncogenes in CC.

Methods

First, we investigated the expression of m6A regulator gene (METTL3) mRNA and proteins by qRT-PCR and western blot assays in cervical cancer cell lines. In addition, we performed a series of functional studies to investigate the oncogenic role of METTL3 and its downstream target oncogenes in CC cells. m6A-methylated RNA immunoprecipitation sequencing (MeRIP-seq) was used to screen the target genes of METTL3. m6A level of mRNA was measured by an m6A-RNA methylation quantification kit.

Results

The level of m6A RNA methylation was significantly increased in CC cells. METTL3 is a major catalytic enzyme involved in the abundant m6A RNA modification and plays an important role in carcinogenesis. We observed that METTL3 expression was frequently up-regulated in CC cell lines. Functional studies with METTL3 knockdown in CC cells dramatically inhibited cellular proliferation, migratory potential and colony formation abilities. Mechanistically, MeRIP-seq illustrated that Yin-Yang 1 (YY1) as a target of METTL3. Recent studies reported that YY1 is highly expressed in different types of cancer, whereby it is associated with cell proliferation, metastasis, survival, metabolic reprogramming, and poor patient survival. The TCGA data analysis revealed that YY1 mRNA and protein were highly expressed cervical cancer tissues. In addition, Pearson correlation analysis showed that highly expressed METTL3 was positively correlated with YY1 expression. Thus, the METTL3/m6A/YY1 axis promotes cervical carcinogenesis.

Conclusions

Taken together, our findings demonstrated the oncogenic role of METTL3 in cervical cancer by regulating YY1 expression in an m6A-dependent manner and provide a new insight into the pathogenesis of CC. Hence, METTL3/m6A/YY1 axis represents a potential target for CC therapy.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

While traditional pelvic exenterations (PE) represent a potentially curative treatment for recurrent tumours localized centrally in the pelvis, new surgical techniques have been developed recently to enable a complete resection even in tumours invading into the pelvic side wall. Extended pelvic exenterations (EPE) include resection of internal, external, or common iliac vessels, pelvic side-wall muscles, large pelvic nerves, or pelvic bones. EPE are currently performed only in a few institutions and data on treatment morbidity are not available. The aim of the study was to compare health-related quality of life (QoL) and oncological outcome after PE and EPE.

Methods

Data from 72 patients with cervical (36), vulvar (19), endometrial (14) and low-grade ovarian (5) cancer who underwent PE (42) or EPE (32) for persistent (20%) or recurrent (80%) disease between 2014 to 2019 at a single tertiary centre were analysed. Quality of life was evaluated in surviving patients using EORTC QLQ-C30, EORTC CX-24, and QOLPEX questionnaire developed specifically for patients after extensive pelvic procedures.

Results

Median overall and disease-specific survival reached in the whole cohort 45 and 49 months, without significant differences between PE and EPE groups (P >0.999). We did not observe any difference in post-surgical complication types or frequency between the groups. Thirty-one survivors participated in the QoL assessment (20 PE, 11 EPE) and no significant differences were found in global health status (P=0.951) or in any of the functional scales. The groups were not differing in therapy satisfaction (P=0.502), and both expressed similar willingness to potentially undergo treatment again (P=0.317) (Table). Table: 47P

EORTC QLQ 30, EORTC QLQ-CX24 – Main results

Conclusions

EPE are associated with similar post-treatment QoL and survival as traditional PE. These procedures represent potentially curative treatment option for patients with persistent or recurrent pelvic cancer invading into pelvic wall structures without further compromising QoL.

Legal entity responsible for the study

The authors.

Funding

Charles University in Prague (UNCE 204065 and PROGRES Q28/LF1).

Disclosure

All authors have declared no conflicts of interest.