Proteomic Profiling of Cervical Cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Hui Qiu
PROVIDER: PXD066743 | iProX | Wed Jul 30 00:00:00 BST 2025
REPOSITORIES: iProX
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Project description:Studies have demonstrated the correlation between kallikrein-related peptidase 5 (KLK5) and cervical cancer prognosis, but studies on the correlation between KLK5 and radiation resistance are rare. Therefore, we aimed to investigate the role of high KLK5 expression in improving radiation resistance in cervical cancer and the underlying mechanisms. Samples from 29 patients with cervical cancer who received definitive radiotherapy without surgical treatment and other antineoplastic treatments (2014–2016) were analyzed. The patients were divided into the radiotherapy-sensitive (RS) group (18 patients without local recurrence and distant metastasis within 3 years after initial treatment) and the radiotherapy-resistant (RR) group (11 patients with uncontrolled conditions with radiotherapy, local recurrence, or distant metastasis within 3 years after initial treatment). We used high-throughput gene sequencing to detect radiosensitivity-related factors. We found that the expression of KLK5 in the RR group was higher than that in the RS group, and this result was associated with poor outcomes after radiotherapy as patients developed distant metastasis and showed recurrence at 2–3 years of follow-up. Besides, a high KLK5 expression enhances radiation resistance, indicating that, with further research, KLK5 may be used to develop novel molecular target-specific modulators for anti-cervical cancer therapy, acting as a prognostic agent in personalized precision medicine for cancer.
2024-11-24 | GSE189721 | GEO
Project description:Preterm birth is a leading cause of neonatal mortality and lacks an effective therapy. Ascending microbial infections from the lower genital tract lead to infection of the placenta, amniotic fluid and fetus causing preterm birth or stillbirth. Directly in the path of an ascending infection is the cervical mucus plug (CMP), a dense mucoid structure in the cervical canal with potential antimicrobial properties. In this study, we aimed to define the components of CMP responsible for antimicrobial activity against a common lower genital tract organism associated with preterm birth and stillbirths, namely Group B Streptococcus (GBS). Using a quantitative proteomic approach, we identified antimicrobial factors in CMPs that were collected from healthy human pregnancies. This study aims to provide new insight into how the human CMP may limit ascending bacterial infection.
2018-02-09 | PXD008600 | Pride
Project description:Purpose: We aimed to investigate the distinct transcriptional landscape in the poor responders to concurrent chemoradiotherapy (CCRT) and to gain mechanistic insights on treatment resistance in cervical cancer. Methods: RNA sequencing was performed using archived pre-treatment tissue biopsies of patients with locally advanced cervical cancer treated with concurrent platinum-based CCRT. Transcriptome data of patients with no durable benefit (NDB; progression-free period < 3 years) and durable clinical benefit (DCB; progression-free period > 5 years) after were compared. NDB score was estimated for each patient using the differentially expressed genes between NDB and DCB patients. Three independent cohorts, including The Cancer Genome Atlas cervical cancer (TCGA-CESC) cohort, were utilized for validation of NDB score. Potential response to PD-1 blockade was estimated with Tumor Immune Dysfunction and Exclusion (TIDE) score and T-cell-inflamed gene expression profile (GEP). Results: Patients with NDB exhibited a distinct transcriptional profile compared to those with DCB such as higher signatures of extracellular matrix organization and epithelial-to-mesenchymal transition. The fraction of cancer-associated fibroblasts (CAFs) within the tumor was significantly higher in NDB than DCB patients. Higher NDB score was significantly associated with poor survival in the TCGA-CESC cohort (n = 274; P = 0.015), but only in patients that received curative aim radiotherapy (P = 0.002) and not in patients who received other treatments (P = 0.57). The transcriptomic characteristics of patients with NDB were recapitulated in patients with high NDB score in TCGA-CESC. Patients with high NDB score displayed significantly higher TIDE prediction score and lower T-cell-inflamed GEP score compared to patients with low NDB scores. Conclusion: Cervical cancer patients with poor treatment outcome following CCRT exhibited a distinct gene signature that was able to predict treatment outcomes. For poor responders, immune checkpoint inhibitors may be less effective and CAF-targeting treatments may be a promising approach.
2021-03-02 | GSE168009 | GEO
Project description:Cervical cancer is still the leading cause of cancer mortality worldwide even after introduction of vaccine against Human papillomavirus (HPV), due to low vaccine coverage, especially in the developing world. Cervical cancer is primarily treated by Chemo/Radiotherapy, depending on the disease stage, with Carboplatin/Cisplatin-based drug regime. These drugs being non-specific, target rapidly dividing cells, including normal cells, so safer options are needed for lower off-target toxicity. Natural products offer an attractive option compared to synthetic drugs due to their well-established safety profile and capacity to target multiple oncogenic hallmarks of cancer like inflammation, angiogenesis, etc. In the current study, we investigated the effect of Bergenin (C-glycoside of 4-O-methylgallic acid), a natural polyphenol compound that is isolated from medicinal plants such as Bergenia crassifolia, Caesalpinia digyna, and Flueggea leucopyrus . Bergenin has been shown to have anti-inflammatory, anti-ulcerogenic, and wound healing properties but its anticancer potential has been realized only recently. We performed a proteomic analysis of cervical carcinoma cells treated with bergenin and found it to influence multiple hallmarks of cancers, including apoptosis, angiogenesis, and tumor suppressor proteins. It was also involved in many different cellular processes unrelated to cancer, as shown by our proteomic analysis. Further analysis showed bergenin to be a potent -angiogenic agent by reducing key angiogenic proteins like Galectin 3 and MMP-9 (Matrix Metalloprotease 9) in cervical carcinoma cells. Further understanding of this interaction was carried out using molecular docking analysis, which indicated MMP-9 has more affinity for bergenin as compared to Galectin-3. Cumulatively, our data provide novel insight into the anti-angiogenic mechanism of bergenin in cervical carcinoma cells by modulation of multiple angiogenic proteins like Galectin-3 and MMP-9 which warrant its further development as an anticancer agent in cervical cancer.
2024-03-04 | PXD043359 | Pride
Project description:Interferon-induced transmembrane proteins (IFITMs) are frequently overexpressed in cancer cells, including cervical carcinoma cells, and play a role in the progression of various cancer types. However, their mechanisms of action remain incompletely understood. In the present study, by employing a combination of surface membrane protein isolation and quantitative mass spectrometry, it was comprehensively described how the IFITM1 protein influences the composition of the cervical cancer cell surfaceome. Additionally, the effects of interferon-γ on protein expression and cell surface exposure were evaluated in the presence and absence of IFITM1. The IFITM1-regulated membrane and membrane-associated proteins identified are involved mainly in processes such as endocytosis and lysosomal transport, cell-cell and cell-extracellular matrix adhesion, antigen presentation and the immune response. To complement the proteomic data, gene expression was analyzed using reverse transcription-quantitative PCR to distinguish whether the observed changes in protein levels were attributable to transcriptional regulation or differential protein dynamics. Furthermore, the proteomic and gene expression data are supported by functional studies demonstrating the impact of the IFITM1 and IFITM3 proteins on the adhesive, migratory and invasive capabilities of cervical cancer cells, as well as their interactions with immune cells.
2025-05-26 | PXD053951 | Pride
Project description:Dynamics of Breast Cancer under Different Rates of Chemoradiotherapy.
Mkango SB1, Shaban N1, Mureithi E1, Ngoma T2.
Author information
1
Department of Mathematics, University of Dar es Salaam, P.O. Box 35062, Dar es Salaam, Tanzania.
2
Department of Clinical Oncology, Muhimbili University of Health and Allied Sciences, P.O. Box 65000, Dar es Salaam, Tanzania.
Abstract
A type of cancer which originates from the breast tissue is referred to as breast cancer. Globally, it is the most common cause of death in women. Treatments such as radiotherapy, chemotherapy, hormone therapy, immunotherapy, and gene therapy are the main strategies in the fight against breast cancer. The present study aims at investigating the effects of the combined radiotherapy and chemotherapy as a way to treat breast cancer, and different treatment approaches are incorporated into the model. Also, the model is fitted to data on patients with breast cancer in Tanzania. We determine new treatment strategies, and finally, we show that when sufficient amount of chemotherapy and radiotherapy with a low decay rate is used, the drug will be significantly more effective in combating the disease while health cells remain above the threshold.
Copyright © 2019 Sara B. Mkango et al.
2020-01-20 | MODEL1912120005 | BioModels
Project description:Cervical cancer is the one of the most prevalent types of cancers in women and is the second highest cause of death in women aged 20-39. The most common chemotherapy for cervical cancer involves the use of the drug cisplatin in conjunction with other therapeutics. However, the development of cisplatin resistance in patients can hinder the efficacy of these treatments. This highlights the need to explore different therapeutic approaches for cervical cancer treatment. We found that inhibitors targeting the enzyme Poly (ADP-ribose) Polymearse (PARP)-1 can attenuate cell growth of cervical adenocarcinoma and squamous cell carcinoma. Furthermore, combinatorial therapy of PARP inhibitors (PARPi) with cisplatin increases the cisplatin-mediated cell toxicity in cervical cancer cells. This is accompanied by a rewiring of the transcriptome in response to the cisplatin and PARPi together. Surprisingly, we observed that the Fos gene is upregulated in the dual treatment condition leading to the subsequent induction of its target genes. Importantly, increased the expression of Fos is sufficient to hinder cervical cancer growth. We conclude that by inducing Fos expression, PARPi treatment with cisplatin leads to inhibition of cervical cancer.
2022-08-02 | GSE176326 | GEO
Project description:We performed a comprehensive proteogenomic profiling of cervical cancer (CC) tumors obtained from 139 Chinese women. This study provides a valuable public resource including proteomic, phosphoproteome, acetylproteome for researchers and clinicians to delve deeper into molecular causes of CC, and to identify potential treatments and advance clinical practice.
2024-10-09 | PXD055203 | Pride