Identification of Novel Biomarker of Human Urinary Bladder Cancer Using High-Density Oligonucleotide Microarray

INTRODUCTION: Urothelial bladder cancer (UBC) is a frequently occurring malignancy of the urinary tract. Treatment of UBC remains a challenge despite advances in surgical, radiotherapy and chemotherapeutic options. Gene expression profiling is an innovative way to identify relevant differentially ex...

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Bibliographic Details
Published in:Indian journal of clinical biochemistry 2022-05, Vol.32 (S1), p.S2
Main Authors: Bhatt, M.L.B, Singh, P.K, Srivastava, A.K, Rath, S.K, Goel, M.M, Dalela, D
Format: Article
Language:English
Subjects:
Analysis
Bladder cancer
Cancer
Care and treatment
Chemotherapy
DNA microarrays
Gene expression
Genes
Health aspects
Immunohistochemistry
RNA
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Summary:INTRODUCTION: Urothelial bladder cancer (UBC) is a frequently occurring malignancy of the urinary tract. Treatment of UBC remains a challenge despite advances in surgical, radiotherapy and chemotherapeutic options. Gene expression profiling is an innovative way to identify relevant differentially expressed candidate genes to be used as molecular bio-markers and novel therapeutic targets. MATERIALAND METHODS: Tissue specimens were obtained from 7 patients with pathologically confirmed non-muscle-invasive (n=2) and invasive (n=5) UBC. Total RNA was extracted from the bladder tumor tissues using TRIzol reagent. Human Bladder Total RNA was used as a universal reference for Affymetrix high-density oligonucleotide microarray analysis. The expression data for each sample was generated on Affymetrix Human Gene 1.1 ST arrays. Subsequently, we validated the expression profile of five differentially expressed cancer-testis (CT) genes (ZNF165, CEP55, PBK/TOPK, TTK and D40) using reverse transcriptase quantitative PCR and immunohistochemistry in another bladder tumour cohort (n = 76) and (n=65). RESULTS: We got 1105 differentially expressed genes which included 380 up-regulated genes and 725 downregulated genes respectively. We observed mRNA overexpression of all five CT genes in testis and UBC patients. CT genes mRNA expression were detected in range of 43%-59% of bladder tumors. Relative mean fold mRNA expression of all five CT genes were found to be significantly (p < 0.01) higher in muscle-invasive bladder cancer as compared to non-muscle-invasive bladder cancer patients. Moreover, Immunohistochemical expression of CT genes was detected in range of 56%70% of bladder tumors. CONCLUSION: We found that all the five CT genes were expressed in a large fraction of bladder tumors and consequently, this may pave the way for successful immunotherapy with high efficiency. The CT genes identified in our study, could serve as a valuable target for development of anticancer agents or cancer peptide vaccines for UBC. KEY WORDS : Urinary Bladder Cancer; Oligonucleotide microarray; Gene expression; Cancer-testis; Peptide vaccine
ISSN:0970-1915