Exploring a Desirable Quadr-mRNAs Panel for Non-invasive and Ultrasensitive Bladder Cancer Diagnosis: In-silico and Clinical Studies

Abstract

Background: Most patients with non-muscle invasive bladder cancer (NMIBC) have a high direction for recurrence and disease progression, which remains a significant unresolved challenge in bladder cancer patients. Therefore, a constant search is necessary for identifying appropriate and reliable biomarkers for early diagnosis of NMIBC. The current study has aimed to search for valuable diagnostic biomarkers in the tissue and urine specimens of NMIBC patients. Methods: The changes of twelve candidate mRNAs in a screening phase (40 tissue samples of NMIBC patients and their corresponding 40 urine specimens) and a subsequent independent validation phase (40 urine specimens) were estimated using real-time polymerase chain reaction (RT-qPCR). The receiver operating characteristic (ROC) analysis was executed to determine the potential diagnostic values of mRNAs. Results: The mRNA levels of seven candidate genes were markedly higher in tissue specimens relative to their neighboring tissues. Among them, four mRNAs, including ERBB2, CCND1, MKI67, and MAGEA6, were differentially expressed in urine samples of NMIBC patients relative to control subjects. Further, the expression of these four mRNAs was validated in the validation step. Combining these biomarkers showed better diagnostic performance than single biomarkers in the urine sample for non-invasive NMIBC detection. The combination of these mRNAs and cytology enhanced the sensitivity of cytology from 37% to 87%. Conclusion: Our findings suggested that a four-mRNA panel may be promising in the non-invasive diagnosis of NMIBC, which deserves further investigation.