Journal

BMC Research Notes

Papers (24)

Genetic analysis of uterine lavage fluids to identify women at high risk of endometrial cancer

Abstract Objectives Endometrial cancer (EC) is the most common malignancy of the female genital tract in developed countries, yet preventive screening remains unavailable, and diagnostic approaches are largely limited to symptomatic women. Despite advancements in precision oncology, the biology of precancerous lesions is less understood compared to advanced disease. To address this gap, we conducted a prospective case-control study analysing uterine lavage fluid from women undergoing diagnostic evaluation. The study included 257 participants: 80 diagnosed with endometrial intraepithelial neoplasia (EIN), 89 with early-stage EC, and 88 healthy controls. Using targeted next-generation sequencing, we examined genetic alterations in 22 selected genes associated with EC development. Results Our findings did not confirm a direct association between specific genetic mutations in uterine lavage fluid and the presence of EIN or early-stage EC (p = 0.501). Mutations were detected in both cases and controls, with a higher overall mutation burden observed in controls, suggesting potential background genomic alterations unrelated to EC development. In conclusion, while molecular profiling of uterine lavage fluid remains a promising concept for non-invasive diagnosis, our results highlight significant challenges in specificity. Further studies with larger cohorts and additional biomarkers are necessary to clarify its diagnostic relevance and clinical applicability.

Proteomics of Ishikawa endometrial cancer cells: impact of liposomal backbone

The Ishikawa cell line is the most widely used model system for investigating implantation and endometrial cancer. Understanding the biology of this cell line is essential for developing effective interventional strategies. To gain a deeper understanding of its cellular protein profile, we extracted cellular proteins from Ishikawa cells and analyzed the peptides using mass spectrometry. Our goal was to create a proteomic resource specifically tailored for Ishikawa cells. This data set is of particular significance in the realm of targeted drug delivery. Liposomes are synthetic spherical vesicles composed of hydrophobic bilayer phospholipids and have received immense recognition as highly effective carriers for the delivery of pharmaceutical drugs and essential nutrients to the endometrium. Phosphatidylcholine and phosphatidylethanolamine are often combined to create functional liposomal systems. To discern any potential interfering effects originating from the liposome backbone, our investigation involved direct effects of phospholipid liposomes on endometrial epithelial cells. The data set includes peptide spectra derived from the intracellular proteomes of Ishikawa endometrial cancer cell isolates and their phospholipid-treated counterparts. Representing a proteome-wide profile, this dataset aims to contribute to a broader understanding of the physiology of endometrial epithelial cells. Proteomic analysis identified key proteins involved in the intricate regulation of cellular metabolism, cell cycle progression, and signaling. Between-group analysis revealed no differentially expressed proteins after adjusting for multiple testing using the applied thresholds (p-value  1). Data are available via ProteomeXchange with identifier PXD050871.

Analysis of miR-497/195 cluster identifies new therapeutic targets in cervical cancer

Abstract Objective miR-497/195, located at 17p13.1, is a highly conserved miRNA cluster whose abnormal expression is a key regulator of carcinogenesis. We performed a comprehensive analysis of the miR-497/195 cluster to determine its prognostic utility and role in cervical cancer (CC) using publicly available datasets. Results In silico analysis and validation revealed that this cluster is downregulated in CC. A total of 60 target genes of miR-497/195 cluster were identified as differentially expressed between normal and CC samples. ShinyGO, STRING, CytoHubba, Timer 2.0, HPA, and HCMBD were used for functional enrichment, PPIN network construction, hub gene identification, immune infiltration correlation, histopathological expression, and determination of the metastatic potential of miR-497/195 cluster and their target genes. PPIN analysis identified CCNE1, CCNE2, ANLN, RACGAP1, KIF23, CHEK1, CDC25A, E2F7, CDK1, and CEP55 as the top 10 hub genes (HGs). Furthermore, the upregulation of RECK, ATD5, and BCL2, downregulation of OSBPL3, RCAN3, and HIST1H3H effected overall survival of CC patients. We identified 6 targets (TFAP2A, CLSPN, RASEF, HIST1H3H, AKT3, and ITPR1) of miR-497/195 cluster to influence metastasis. In addition, 8 druggable genes and 38 potential drugs were also identified. Our study identified miR-497/195 cluster target genes and pathways that could be used for prognostic and therapeutic applications in CC.

Analysis of the first inpatient expenditure for cervical cancer patients before and during the COVID-19 pandemic in a provincial maternal and children care hospital in China

COVID-19 has led to economic difficulties for many cancer patients. This study aimed to identify the trend and the major cost items of inpatient expenditure for the admittance to hospital for cervical cancer patients in Hunan Province Maternal and Children Care Hospital from 2017 to 2021. This study assessed the composition of inpatient expenditure using the gray correlation method and the variation in the hospitalization expense structure using the degree of structural variation. A total of 909 patients were identified. The median age of the patients was 49±10.25 years. Insurance payments for cancer patients accounted for 33.51% before the COVID-19 pandemic (2017-2019) but increased to 80.29% during the pandemic (2020-2021). Diagnosis costs accounted for the largest proportion of medical expenditure every year and showed an increasing trend during the study period. Although the consumables cost accounted for the lowest proportion of total costs each year, they showed a fluctuating growth trend with an average annual growth rate of 23.54%, which was the only fluctuation cost of the six constituents. Drug cost had the only positive value for the structural variation of total medical expenditure over the five years. The proportion of hospitalization expenses paid by insurance after COVID-19 is higher than that paid before COVID-19. Attention should be paid to the rising costs of drugs after the COVID-19 pandemic and reasonable control should be maintained for the diagnosis costs to reduce the total expenditure on cervical cancer patients after COVID-19.

Specific transcriptional signature dataset of extracellular signal-regulated kinase 5 in leiomyosarcoma derived cell lines

Soft-tissue sarcomas, particularly leiomyosarcomas, are aggressive tumors characterized by limited therapeutic options due to an insufficient understanding of their molecular drivers. To identify novel therapeutic targets, we investigated the role of Extracellular signal-regulated kinase-5 (ERK5), a critical signaling protein in soft-tissue sarcoma biology. The primary objective was to define the transcriptomic profile specifically associated with ERK5, enhancing the understanding of molecular mechanisms underlying leiomyosarcoma. Two uterine leiomyosarcoma cell lines, SK-UT-1 and AA, underwent ERK5 genetic knockdown via lentiviral transduction with shRNA followed by puromycin selection. Knockdown efficiency was confirmed through RT-qPCR and Western blotting. RNA sequencing was performed using the DNBSEQ platform. Raw reads underwent quality filtering and were aligned to the human genome (GRCh38.p13) with Bowtie2. Gene expression was quantified by RSEM, and differential expression analysis was conducted with DESeq2 (|log2FC|≥ 1, q-value ≤ 0.05). As a result, we identified 1218 and 227 differentially expressed genes for AA and SK-UT-1 respectively, and 81 in common for both cell lines. The raw and RNAseq data and sequences are available at the NCBI GEO repository under GSE297879. Sequence comparison could reveal new therapeutic targets based on the ERK5 signalling pathway, which is critical in experimental models of soft-tissue sarcoma.

The participation in cervical cancer screening is not altered by the Hawthorne effect among patients of doctors participating in the randomized clinical trial PaCUDAHL

The PaCUDAHL randomized clinical trial evaluated an HPV self-sampling device provided by the family doctor to female patients not participating in the usual opportunistic cervical screening program from 2016 to 2019. Reliable data on the Hawthorne (observer) effect (HE) in clinical trials were lacking. This nested study aimed to verify whether there was a significant difference between participating and non-participating general practitioners (GPs) in the trial, and to measure whether there was an HE in the female patients of participating GPs. We carried out an analytical retrospective cohort study involving 332 GPs and their 70,983 female patients, aged 25-65, registered with the Health Insurance Fund of Flanders, using claims database for the three-year periods 2012-2015 and 2016-2019. Statistical analyses were performed using a linear generalized hierarchical mixed model with geographic level as a random effect. The patients of the 24 participating GPs did not have a cervical cancer screening rate different from that of the non-participating GPs, either before recruitment (p = 0.24) or during the PaCUDAHL trial period (p = 0.15). There were significant increases in cervical cancer screening rates over four years regardless of the group considered (p < 0.0001). In conclusion there was no observer effect but a significant cohort effect.

Analysis of inflammation parameter value lymphocyte monocyte ratio (LMR), platelet lymphocyte ratio (PLR), and systemic inflammation response index (SIRI) to differentiate malignant and benign ovarian tumors

Ovarian cancer is the leading cause of death from gynecological cancers. In the early stages, it is generally asymptomatic, leading to delays in the early diagnosis of ovarian cancer. Inflammation, which is the body's response to tissue damage, plays a crucial role in the pathogenesis of cancer. Inflammatory responses result in cellular changes, damaged tissue repair, and affected area proliferation. This research aims to determine the differences in LMR (Lymphocyte-to-Monocyte Ratio), PLR (Platelet-to-Lymphocyte Ratio), and SIRI (Systemic Immune-Inflammation Index), which were the parameters of inflammation between ovarian malignant tumors and benign ovarian tumors. This retrospective cohort study analyzed medical records of 327 patients treated at Dr. Hasan Sadikin General Hospital, Bandung, between 2020 and 2022, including 166 cases of malignant ovarian tumors and 161 benign ovarian tumors. Inflammatory markers were calculated from routine blood counts. The mean LMR was significantly lower in the malignant group than the benign group (3.32 vs. 3.83, P = 0.004). Conversely, PLR and SIRI values were significantly higher in malignant tumors (PLR: 355 vs. 213, P = 0.001; SIRI: 3.50 vs. 2.97, P = 0.042). These findings suggest that LMR, PLR, and SIRI may serve as supportive inflammatory biomarkers in distinguishing malignant from benign ovarian tumors.

Publisher

Springer Science and Business Media LLC

ISSN

1756-0500