RAIDS atlas of significant genetic and protein biomarkers in cervical cancer.
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ABSTRACT:
SUBMITTER: Scholl S
PROVIDER: S-EPMC10482580 | biostudies-literature | 2023 Sep
REPOSITORIES: biostudies-literature
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RAIDS atlas of significant genetic and protein biomarkers in cervical cancer.
Scholl Suzy S Roufai Diana Bello DB Chérif Linda Larbi LL Kamal Maud M
Journal of gynecologic oncology 20230901 5
Loss of function in epigenetic acting genes together with driver alterations in the PIK3CA pathway have been shown significantly associated with poor outcome in cervical squamous cell cancer. More recently, a CoxBoost analysis identified 16 gene alterations and 30 high level activated proteins to be of high interest, due to their association with either good or bad outcome, in the context of treatment received by chemoradiation. The objectives here were to review and confirm the significance of ...[more]
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Project description:BackgroundCervical cancer (CC) is -second to breast cancer- a dominant cause of gynecological cancer-related deaths worldwide. CC tumor biopsies and blood samples are of easy access and vital for the development of future precision medicine strategies.DesignBIO-RAIDs is a prospective multicenter European study, presently recruiting patients in 6 EU countries. Tumor and liquid biopsies from patients with previously non-treated cervical cancer (stages IB2-IV) are collected at defined time points. Patients receive standard primary treatment according to the stage of their disease. 700 patients are planned to be enrolled. The main objectives are the discovery of -dominant molecular alterations, -signalling pathway activation, and -tumor micro-environment patterns that may predict response or resistance to treatment. An exhaustive molecular analysis is performed using 1° Next generation sequencing, 2° Reverse phase protein arrays and 3° Immuno-histochemistry.DiscussionThe clinical study BIO-RAIDs is activated in all planned countries, 170 patients have been recruited till now. This study will make an important contribution towards precision medicine treatments in cervical cancer. The results will support the development of clinical practice guidelines for cervical cancer patients to improve their prognosis and their quality of life.Trial registrationClinicaltrials.gov: NCT02428842 , registered 10 February 2015.
| S-EPMC4632364 | biostudies-literature
Project description:Cervical cancer is the leading cause of death with gynecological malignancies. We aimed to explore the molecular mechanism of carcinogenesis and biomarkers for cervical cancer by integrated bioinformatic analysis. We employed RNA-sequencing details of 254 cervical squamous cell carcinomas and 3 normal samples from The Cancer Genome Atlas. To explore the distinct pathways, messenger RNA expression was submitted to a Gene Set Enrichment Analysis. Kyoto Encyclopedia of Genes and Genomes and protein-protein interaction network analysis of differentially expressed genes were performed. Then, we conducted pathway enrichment analysis for modules acquired in protein-protein interaction analysis and obtained a list of pathways in every module. After intersecting the results from the 3 approaches, we evaluated the survival rates of both mutual pathways and genes in the pathway, and 5 survival-related genes were obtained. Finally, Cox hazards ratio analysis of these 5 genes was performed. DNA replication pathway ( P < .001; 12 genes included) was suggested to have the strongest association with the prognosis of cervical squamous cancer. In total, 5 of the 12 genes, namely, minichromosome maintenance 2, minichromosome maintenance 4, minichromosome maintenance 5, proliferating cell nuclear antigen, and ribonuclease H2 subunit A were significantly correlated with survival. Minichromosome maintenance 5 was shown as an independent prognostic biomarker for patients with cervical cancer. This study identified a distinct pathway (DNA replication). Five genes which may be prognostic biomarkers and minichromosome maintenance 5 were identified as independent prognostic biomarkers for patients with cervical cancer.
| S-EPMC5900817 | biostudies-literature
Project description:ObjectivesCervicovaginal fluid (CVF) can be considered as a potential source of biomarkers for diseases of the lower female reproductive tract. The fluid can easily be collected, thereby offering new opportunities such as the development of self tests. Our objective was to identify a CVF protein biomarker for cervical cancer or its precancerous state.MethodsA differential proteomics study was set up using CVF samples from healthy and precancerous women. Label-free spectral counting was applied to quantify protein abundances.ResultsThe proteome analysis revealed 16 candidate biomarkers of which alpha-actinin-4 (p = 0.001) and pyruvate kinase isozyme M1/M2 (p = 0.014) were most promising. Verification of alpha-actinin-4 by ELISA (n = 28) showed that this candidate biomarker discriminated between samples from healthy and both low-risk and high-risk HPV-infected women (p = 0.009). Additional analysis of longitudinal samples (n = 29) showed that alpha-actinin-4 levels correlated with virus persistence and clearing, with a discrimination of approximately 18 pg/ml.ConclusionsOur results show that CVF is an excellent source of protein biomarkers for detection of lower female genital tract pathologies and that alpha-actinin-4 derived from CVF is a promising candidate biomarker for the precancerous state of cervical cancer. Further studies regarding sensitivity and specificity of this biomarker will demonstrate its utility for improving current screening programs and/or its use for a cervical cancer self-diagnosis test.
| S-EPMC4162552 | biostudies-literature
Project description:We developed a discovery-validation mass-spectrometry based pipeline to identify a set of proteins that are regulated in serum of patients with cervical intraepithelial neoplasia (CIN) and squamous cell cervical cancer using isobaric Tags for Relative and Absolute Quantitation (iTRAQ®), label-free shotgun and targeted mass-spectrometric quantification. At the discovery stage we used a “pooling” strategy for the comparative analysis of immunodepleted serum from patients with early-(CES) and late-stage (CLS) cervical cancer versus healthy controls that revealed 15 up- and 26 down-regulated proteins. The analysis of non-depleted serum samples from patients with CIN, CES, CLS, and healthy controls showed significant changes in abundance of alpha-1-acid glycoprotein 1, alpha-1-antitrypsin, serotransferrin, haptoglobin, alpha-2-HS-glycoprotein and vitamin D-binding protein. To further validate our findings we developed a fast UPLC/MRM method for the simultaneous targeted quantification of these proteins in an independent set of serum from patients with cervical cancer or CIN and healthy controls as well as serum samples from patients with ovarian cancer. The panel of six proteins showed 72 % sensitivity and 82 % specificity for discrimination of patients with CIN from healthy controls, a stage of the disease where current protein-based biomarkers, e.g. squamous cell carcinoma antigen fail to show any discrimination.
2014-10-06 | PXD001055 | Pride
Project description:OBJECTIVE:To screen potential plasma protein biomarkers for the progression of cervical precancerous lesions into cervical carcinoma and analyze their functions. METHODS:Plasma samples obtained from healthy control subjects, patients with low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), cervical cancer (CC), and patients with CC after treatment were enriched for low-abundance proteins for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The MS data of the samples were analyzed using Discoverer 2.2 software, and the differential proteins (peptide coverage ≥20%, unique peptides≥2) were screened by comparison of LSIL, HSIL and CC groups against the control group followed by verification using target proteomics technology. Protein function enrichment and coexpression analyses were carried out to explore the role of the differentially expressed proteins as potential biomarkers and their pathological mechanisms. RESULTS:Compared with the control group, both LSIL group and HSIL group showed 9 differential proteins; 5 differentially expressed proteins were identified in CC group. The proteins ORM2 and HPR showed obvious differential expressions in LSIL and HSIL groups compared with the control group, and could serve as potential biomarkers for the progression of cervical carcinoma. The expression of F9 increased consistently with the lesion progression from LSIL to HSIL and CC, suggesting its value as a potential biomarker for the progression of cervical cancer. CFI and AFM protein levels were obviously decreased in treated patients with CC compared with the patients before treatment, indicating their predictive value for the therapeutic efficacy. Protein function enrichment analysis showed that all these differentially expressed proteins were associated with the complement system and the coagulation cascades pathway. CONCLUSIONS:We identified 5 new protein biomarkers (F9, CFI, AFM, HPR, and ORM2) for cervical precancerous lesions and for prognostic evaluation of CC, and combined detection of these biomarkers may help in the evaluation of the development and progression of CC and also in improving the diagnostic sensitivity and specificity of cervical lesions.
| S-EPMC6765587 | biostudies-literature
Project description:We developed a discovery-validation mass-spectrometry based pipeline to identify a set of proteins that are regulated in serum of patients with cervical intraepithelial neoplasia (CIN) and squamous cell cervical cancer using isobaric Tags for Relative and Absolute Quantitation (iTRAQ®), label-free shotgun and targeted mass-spectrometric quantification. At the discovery stage we used a â??poolingâ?? strategy for the comparative analysis of immunodepleted serum from patients with early-(CES) and late-stage (CLS) cervical cancer versus healthy controls that revealed 15 up- and 26 down-regulated proteins. The analysis of a new of non-depleted serum samples from patients with CIN, CES, CLS, and healthy controls showed significant changes in abundance of alpha-1-acid glycoprotein 1, alpha-1-antitrypsin, serotransferrin, haptoglobin, alpha-2-HS-glycoprotein and vitamin D-binding protein. To further validate our findings we developed a fast UPLC/MRM method for the simultaneous targeted quantification of these proteins in a new set of 48 CIN, 50 CES, 34 CLS and 48 healthy controls as well as 49 serum samples from patients with ovarian cancer. The panel of six proteins showed 62% sensitivity and 82 % specificity for discrimination of patients with CIN grade 2 or worse from healthy controls, a stage of the disease where current protein-based biomarkers fail to show any discrimination.
2016-07-19 | MSV000079925 | MassIVE
Project description:We developed a discovery-validation mass-spectrometry based pipeline to identify a set of proteins that are regulated in serum of patients with cervical intraepithelial neoplasia (CIN) and squamous cell cervical cancer using isobaric Tags for Relative and Absolute Quantitation (iTRAQ®), label-free shotgun and targeted mass-spectrometric quantification. At the discovery stage we used a “pooling” strategy for the comparative analysis of immunodepleted serum from patients with early-(CES) and late-stage (CLS) cervical cancer versus healthy controls that revealed 15 up- and 26 down-regulated proteins. The analysis of a new of non-depleted serum samples from patients with CIN, CES, CLS, and healthy controls showed significant changes in abundance of alpha-1-acid glycoprotein 1, alpha-1-antitrypsin, serotransferrin, haptoglobin, alpha-2-HS-glycoprotein and vitamin D-binding protein. To further validate our findings we developed a fast UPLC/MRM method for the simultaneous targeted quantification of these proteins in a new set of 48 CIN, 50 CES, 34 CLS and 48 healthy controls as well as 49 serum samples from patients with ovarian cancer. The panel of six proteins showed 62% sensitivity and 82 % specificity for discrimination of patients with CIN grade 2 or worse from healthy controls, a stage of the disease where current protein-based biomarkers fail to show any discrimination.
2014-10-06 | PXD001034 | Pride
Project description:BackgroundProstate cancer progresses slowly when present in low risk forms but can be lethal when it progresses to metastatic disease. A non-invasive test that can detect significant prostate cancer is needed to guide patient management.MethodsCapillary electrophoresis/mass spectrometry has been employed to identify urinary peptides that may accurately detect significant prostate cancer. Urine samples from 823 patients with PSA (<15 ng/ml) were collected prior to biopsy. A case-control comparison was performed in a training set of 543 patients (nSig = 98; nnon-Sig = 445) and a validation set of 280 patients (nSig = 48, nnon-Sig = 232). Totally, 19 significant peptides were subsequently combined by a support vector machine algorithm.ResultsIndependent validation of the 19-biomarker model in 280 patients resulted in a 90% sensitivity and 59% specificity, with an AUC of 0.81, outperforming PSA (AUC = 0.58) and the ERSPC-3/4 risk calculator (AUC = 0.69) in the validation set.ConclusionsThis multi-parametric model holds promise to improve the current diagnosis of significant prostate cancer. This test as a guide to biopsy could help to decrease the number of biopsies and guide intervention. Nevertheless, further prospective validation in an external clinical cohort is required to assess the exact performance characteristics.
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Project description:Although cancer cell secretome profiling is a promising strategy used to identify potential body fluid-accessible cancer biomarkers, questions remain regarding the depth to which the cancer cell secretome can be mined and the efficiency with which researchers can select useful candidates from the growing list of identified proteins. Therefore, we analyzed the secretomes of 23 human cancer cell lines derived from 11 cancer types using one-dimensional SDS-PAGE and nano-LC-MS/MS performed on an LTQ-Orbitrap mass spectrometer to generate a more comprehensive cancer cell secretome. A total of 31,180 proteins was detected, accounting for 4,584 non-redundant proteins, with an average of 1,300 proteins identified per cell line. Using protein secretion-predictive algorithms, 55.8% of the proteins appeared to be released or shed from cells. The identified proteins were selected as potential marker candidates according to three strategies: (i) proteins apparently secreted by one cancer type but not by others (cancer type-specific marker candidates), (ii) proteins released by most cancer cell lines (pan-cancer marker candidates), and (iii) proteins putatively linked to cancer-relevant pathways. We then examined protein expression profiles in the Human Protein Atlas to identify biomarker candidates that were simultaneously detected in the secretomes and highly expressed in cancer tissues. This analysis yielded 6-137 marker candidates selective for each tumor type and 94 potential pan-cancer markers. Among these, we selectively validated monocyte differentiation antigen CD14 (for liver cancer), stromal cell-derived factor 1 (for lung cancer), and cathepsin L1 and interferon-induced 17-kDa protein (for nasopharyngeal carcinoma) as potential serological cancer markers. In summary, the proteins identified from the secretomes of 23 cancer cell lines and the Human Protein Atlas represent a focused reservoir of potential cancer biomarkers.
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