Cell‐free lncRNA expression signatures in urine serve as novel non‐invasive biomarkers for diagnosis and recurrence prediction of bladder cancer

Abstract

Cell‐free long non‐coding RNAs (lncRNAs) are stably present in urine and can serve as non‐invasive biomarkers for cancer. We aimed to identify signatures of lncRNAs in urine for diagnosis and prognosis of bladder cancer (BC). Screening of lncRNAs by microarray analysis was performed using urine samples of 10 BC patients and 10 controls. Expressions of candidate lncRNAs were evaluated in the training and validation set including 230 BC patients and 230 controls by quantitative reverse transcription polymerase chain reaction (qRT‐PCR). A two‐lncRNA panel (uc004cox.4 and GAS5) was constructed and provided high diagnostic accuracy of BC with an area under the curve (AUC) of 0.885 (95% CI, 0.836‐0.924). The AUCs of the lncRNA panel for Ta, T1 and T2‐T4 were 0.843, 0.867 and 0.923, respectively, significantly higher than those of urine cytology (all P < .05). Kaplan‐Meier analysis revealed that higher level of uc004cox.4 was associated with poor recurrence‐free survival (RFS) of non‐muscle invasive BC (NMIBC) (P = .008). Additionally, Cox regression analysis indicated that uc004cox.4 was an independent prognostic factor for RFS of NMIBC (P = .018). Taken together, our findings indicated that urinary lncRNA signatures possessed potential clinical value for BC diagnosis. Moreover, uc004cox.4 could provide prognostic information for NMIBC.

A Panel of Urinary Long Non-coding RNAs Differentiate Bladder Cancer from Urocystitis

“…Recently, several reports have highlighted the role of long non-coding RNAs (lncRNAs) as urine-based biomarkers for diagnosis of bladder cancer [1,[10][11][12][13][14][15][16][17][18][19][20][21][22]. Long non-coding RNAs are transcripts longer than 200 nucleotides that are not translated into protein [23].…”

“…Another study [14] showed that overexpression of several lncRNAs, such as HOTAIR, HOX-AS-2, MALAT1, HYMAI, LINC00477, LOC100506688 and OTX2-AS1, has been found in urine exosomes of high-grade MIBC patients. Several other studies [10,12] also proposed various panels of lncRNAs as liquid biopsy biomarkers to discriminate bladder cancer patients from healthy controls.…”

“…At time of diagnosis, non-muscle invasive bladder cancer (NMIBC) represents the majority of cases, accounting for 70% [1][2][3][4][5][6][7][8][9]. Early diagnosis and treatment of cancerous or precancerous lesions is thought to be important for reducing the risk of relapse and improving the prognosis of NMIBC [10].…”

Uncovering the potential of CD44v/SYNE1/miR34a axis in salivary fluids of oral cancer patients

“…Although this approach is extremely promising, the stability of RNA and miRNAs in the bodily fluids has been questioned time and again attributed to the numerous RNases compelling it to degrade quickly. Conversely, several reports showed stability and consistency of these cfRNAs and cfmiRNAs, thus supporting their potential to be used as a biomarker for various malignancies . In spite of there being several salivary and serum proteomic, metabolomics, genomic, and transcriptomic biomarkers that have been widely used and explored over the past decades, however, biomarker exclusively specific for OSCC is yet to be determined.…”

“…Conversely, several reports showed stability and consistency of these cfRNAs and cfmiRNAs, thus supporting their potential to be used as a biomarker for various malignancies. [15][16][17][18] In spite of there being several salivary and serum proteomic, metabolomics, genomic, and transcriptomic biomarkers 19 that have been widely used and explored over the past decades, however, biomarker exclusively specific for OSCC is yet to be determined. Hence, the unearthing of serum and salivary biomarkers is a dynamic and evolving field in the regime of oral squamous cell carcinoma.…”