Editorial: Identifying novel biomarkers in bladder cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Ecke TH
PROVIDER: S-EPMC10353301 | biostudies-literature | 2023
REPOSITORIES: biostudies-literature
Publications
Editorial: Identifying novel biomarkers in bladder cancer.
Ecke Thorsten H TH Lotan Yair Y Massfelder Thierry T
Frontiers in oncology 20230704
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Project description:Background: Breast cancer is a heterogeneous neoplasm. Distinct subtypes of breast cancer have been defined, suggesting the existence of molecular differences contributing to their clinical outcomes. However, the molecular differences between HER2 positive and negative breast cancer tumors remain unclear. Objective: The aim of this study was to identify a gene expression profile for breast tumors based on HER2 status. Material and methods: The HER2 status was determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in 54 breast tumor samples. Using Affymetrix microarray data from these breast tumors, we established the expression profiling of breast cancer based on HER2 IHC and FISH results. To validate microarray experiment data, real-time quantitative reverse transcription-PCR was performed. Results: We found significant differences between the HER2-positive and HER2-negative breast tumor samples, which included overexpression of HER2, as well as other genes located on 17q12, and genes functionally related to migration. Conclusion: Our study shows the potential of integrated genomics profiling to shed light on the molecular knowledge of HER2-positive breast tumors. The tumor samples under study correspond to 54 primary breast carcinomas. They included 15 cases with a HER2 IHC3+ score with HER2 gene amplification, 13 cases with IHC2+ score with amplification and 13 without HER2 gene amplification, and 13 cases IHC0/1+ score without HER2 gene amplification. 12 samples of breast normal tissues from breast cancer patients were also included as a reference. Neither overexpression nor amplification of HER2 was observed.
2011-12-22 | E-GEOD-29431 | biostudies-arrayexpress
Project description:Background: Breast cancer is a heterogeneous neoplasm. Distinct subtypes of breast cancer have been defined, suggesting the existence of molecular differences contributing to their clinical outcomes. However, the molecular differences between HER2 positive and negative breast cancer tumors remain unclear. Objective: The aim of this study was to identify a gene expression profile for breast tumors based on HER2 status. Material and methods: The HER2 status was determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in 54 breast tumor samples. Using Affymetrix microarray data from these breast tumors, we established the expression profiling of breast cancer based on HER2 IHC and FISH results. To validate microarray experiment data, real-time quantitative reverse transcription-PCR was performed. Results: We found significant differences between the HER2-positive and HER2-negative breast tumor samples, which included overexpression of HER2, as well as other genes located on 17q12, and genes functionally related to migration. Conclusion: Our study shows the potential of integrated genomics profiling to shed light on the molecular knowledge of HER2-positive breast tumors.
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Project description:Extracellular RNA (exRNA) is an emerging paradigm as endocrine signals in cellular communication, biomarker development, therapeutic applications and systemic physiology. This project is to test the hypothesis that salivary extracellular RNA (exRNA) can be developed for the clinical detection of human diseases. Our laboratory first reported the existence of a transcriptome and microRNA profile in cell free saliva followed by its scientific characterizations and clinical utilities including biomarker development for molecular oncology applications. Most recently we have performed RNA-sequencing in cell free saliva and reported three major types of RNA in saliva (mRNA, miRNA and snoRNA). This study is to test the hypothesis that salivary exRNA can be developed to detect gastric cancer by performing a biomarker development study to definitively validate salivary exRNA biomarkers for the detection of gastric cancer.
2018-10-27 | GSE121870 | GEO
Project description:In the case of bladder cancer, carcinoma in situ (CIS) is known to have poor diagnosis. However, there are not enough studies that examine the biomarkers relevant to CIS development. Omics experiments generate data with tens of thousands of descriptive variables, e.g., gene expression levels. Often, many of these descriptive variables are identified as somehow relevant, resulting in hundreds or thousands of relevant variables for building models or for further data analysis. We analyze one such dataset describing patients with bladder cancer, mostly non-muscle-invasive (NMIBC), and propose a novel approach to feature selection. This approach returns high-quality features for prediction and yet allows interpretability as well as a certain level of insight into the analyzed data. As a result, we obtain a small set of seven of the most-useful biomarkers for diagnostics. They can also be used to build tests that avoid the costly and time-consuming existing methods. We summarize the current biological knowledge of the chosen biomarkers and contrast it with our findings.
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Project description:BackgroundBladder cancer (BCa) remains a lethal malignancy that can be cured if detected early. DNA hypermethylation is a common epigenetic abnormality in cancer that may serve as a marker of disease activity.MethodsWe selected 10 novel candidate genes from the most frequently hypermethylated genes detected by DNA microarray and bisulfite pyrosequencing of bladder cancers and applied them to detect bladder cancer in urine sediments. We analyzed DNA methylation in the candidate genes by quantitative methylation-specific real-time PCR (qMSP) to detect bladder cancer in urine sediments from 128 bladder cancer patients and 110 age-matched control subjects.ResultsBased on a multigene predictive model, we discovered 6 methylation markers (MYO3A, CA10, SOX11, NKX6-2, PENK, and DBC1) as most promising for detecting bladder cancer. A panel of 4 genes (MYO3A, CA10, NKX6-2, and DBC1 or SOX11) had 81% sensitivity and 97% specificity, whereas a panel of 5 genes (MYO3A, CA10, NKX6-2, DBC1, and SOX11 or PENK) had 85% sensitivity and 95% specificity for detection of bladder cancer (area under curve = 0.939). By analyzing the data by cancer invasiveness, detection rate was 47 of 58 (81%) in non-muscle invasive tumors (pTa, Tis, and pT1) and 62 of 70 (90%) in muscle invasive tumors (T2, T3, and T4).ConclusionsThis biomarker panel analyzed by qMSP may help the early detection of bladder tumors in urine sediments with high accuracy.ImpactThe panel of biomarker deserves validation in a large well-controlled prospectively collected sample set.
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Project description:Bladder cancer is a molecularly heterogeneous disease characterized by multiple unmet needs in the realm of diagnosis, clinical staging, monitoring and therapy. There is an urgent need to develop precision medicine for advanced urothelial carcinoma. Given the difficulty of serial analyses of metastatic tumor tissue to identify resistance and new therapeutic targets, development of non-invasive monitoring using circulating molecular biomarkers is critically important. Although the development of circulating biomarkers for the management of bladder cancer is in its infancy and may currently suffer from lower sensitivity of detection, they have inherent advantages owing to non-invasiveness. Additionally, circulating molecular alterations may capture tumor heterogeneity without the sampling bias of tissue biopsy. This review describes the accumulating data to support further development of circulating biomarkers including circulating tumor cells, cell-free circulating tumor (ct)-DNA, RNA, micro-RNA and proteomics to improve the management of bladder cancer.
| S-EPMC5181678 | biostudies-literature
Project description:More than 380,000 new cases of bladder cancer are diagnosed worldwide, accounting for ∼150,200 deaths each year. To discover potential biomarkers of bladder cancer, we employed a strategy combining laser microdissection, isobaric tags for relative and absolute quantitation labeling, and liquid chromatography-tandem MS (LC-MS/MS) analysis to profile proteomic changes in fresh-frozen bladder tumor specimens. Cellular proteins from four pairs of surgically resected primary bladder cancer tumor and adjacent nontumorous tissue were extracted for use in two batches of isobaric tags for relative and absolute quantitation experiments, which identified a total of 3220 proteins. A DAVID (database for annotation, visualization and integrated discovery) analysis of dysregulated proteins revealed that the three top-ranking biological processes were extracellular matrix organization, extracellular structure organization, and oxidation-reduction. Biological processes including response to organic substances, response to metal ions, and response to inorganic substances were highlighted by up-expressed proteins in bladder cancer. Seven differentially expressed proteins were selected as potential bladder cancer biomarkers for further verification. Immunohistochemical analyses showed significantly elevated levels of three proteins-SLC3A2, STMN1, and TAGLN2-in tumor cells compared with noncancerous bladder epithelial cells, and suggested that TAGLN2 could be a useful tumor tissue marker for diagnosis (AUC = 0.999) and evaluating lymph node metastasis in bladder cancer patients. ELISA results revealed significantly increased urinary levels of both STMN1 and TAGLN2 in bladder cancer subgroups compared with control groups. In comparisons with age-matched hernia urine specimens, urinary TAGLN2 in bladder cancer samples showed the largest fold change (7.13-fold), with an area-under-the-curve value of 0.70 (p < 0.001, n = 205). Overall, TAGLN2 showed the most significant overexpression in individual bladder cancer tissues and urine specimens, and thus represents a potential biomarker for noninvasive screening for bladder cancer. Our findings highlight the value of bladder tissue proteome in providing valuable information for future validation studies of potential biomarkers in urothelial carcinoma.
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