Microsatellite Instability Analysis (MSA) for Bladder Cancer: Past History and Future Directions

Abstract

Microsatellite instability (MSI), the spontaneous loss or gain of nucleotides from repetitive DNA tracts, is a diagnostic phenotype for gastrointestinal, endometrial, colorectal, and bladder cancers; yet a landscape of instability events across a wider variety of cancer types is beginning to be discovered. The epigenetic inactivation of the MLH1 gene is often associated with sporadic MSI cancers. Recent next-generation sequencing (NGS)-based analyses have comprehensively characterized MSI-positive (MSI+) cancers, and several approaches to the detection of the MSI phenotype of tumors using NGS have been developed. Bladder cancer (here we refer to transitional carcinoma of the bladder) is a major cause of morbidity and mortality in the Western world. Cystoscopy, a gold standard for the detection of bladder cancer, is invasive and sometimes carries unwanted complications, while its cost is relatively high. Urine cytology is of limited value due to its low sensitivity, particularly to low-grade tumors. Therefore, over the last two decades, several new “molecular assays” for the diagnosis of urothelial cancer have been developed. Here, we provide an update on the development of a microsatellite instability assay (MSA) and the development of MSA associated with bladder cancers, focusing on findings obtained from urine analysis from bladder cancer patients as compared with individuals without bladder cancer. In our review, based on over 18 publications with approximately 900 sample cohorts, we provide the sensitivity (87% to 90%) and specificity (94% to 98%) of MSA. We also provide a comparative analysis between MSA and other assays, as well as discussing the details of four different FDA-approved assays. We conclude that MSA is a potentially powerful test for bladder cancer detection and may improve the quality of life of bladder cancer patients.

Apoptosis related genes mediated molecular subtypes depict the hallmarks of the tumor microenvironment and guide immunotherapy in bladder cancer

“…TMB is greatly influenced by the equipment of different laboratories, and the level of TMB in BLCA was not significant [ 49 ]. In contrast, MSI or MMR occurs in only 2–3% of BLCA patients [ 50 ]. Through our research, we have confirmed the influence of ARGscore on the prognosis and immunotherapy of BLCA patients who received ICIs treatment.…”

CDKN3 Overcomes Bladder Cancer Cisplatin Resistance via LDHA-Dependent Glycolysis Reprogramming

“… 4 The onset of BLCA occurs due to the lack of cancer-specific Clinical symptoms, almost 25% incidence of patients with muscularis infiltration when diagnosed. 5 , 6 The surgery, chemotherapy, radiotherapy and immunotherapy are extensively applied for BLCA patients. Presently, cisplatin-based neoadjuvant chemotherapy is the major regimen for BLCA treatment, including GC (gemcitabine and cisplatin) or M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin).…”

Detection of Urinary Molecular Marker Test in Urothelial Cell Carcinoma: A Review of Methods and Accuracy

“…This process plays a crucial role in the different stages of human carcinogenesis. Microsatellite markers are presently detected through the examination of PCR products from important microsatellite markers (MSI-PCR) [ 29 ]. It has been reported that numerous groups have generated techniques for analyzing MSI using extensive parallel DNA-sequencing technologies in recent years [ 30 ].…”

“…Besides offering solid precision, both qualitative and quantitative, this recent approach is also based on a high number of samples. As well as identifying valuable biomarkers and new therapeutic targets for MSI-positive carcinogenesis, next-generation sequencing (NGS) has become a useful tool [ 29 ]. These are the latest advances in the study of MSI + (MSI positive) carcinogenesis [ 29 , 44 , 45 , 46 ].…”

“…As well as identifying valuable biomarkers and new therapeutic targets for MSI-positive carcinogenesis, next-generation sequencing (NGS) has become a useful tool [ 29 ]. These are the latest advances in the study of MSI + (MSI positive) carcinogenesis [ 29 , 44 , 45 , 46 ]. As a result of the initial studies on Lynch syndrome, numerous studies of MSI for a diversity of human carcinogens have led to three key conclusions.…”