Circulating miRNA panels for specific and early detection in bladder cancer

Abstract

Bladder cancer is the 9th leading cause of cancer death worldwide. The major problem in bladder cancer is primarily the high recurrence rate after drug treatment and resection. Although conventional screening methods, such as cystoscopy, urinary cytology and ultrasound sonography, have become widely used in clinical settings, the diagnostic performance of these modalities is unsatisfactory due to low accuracy or high invasiveness. Because circulating micro RNA (miRNA) profiles have recently been reported as an attractive tool for liquid biopsy in cancer screening, here, we performed global miRNA profiling of 392 serum samples of bladder cancer patients with 100 non‐cancer samples and 480 samples of other types of cancer as controls. We randomly classified the bladder cancer and control samples into 2 cohorts, a training set (N = 486) and a validation set (N = 486). By comparing both controls, we identified specific miRNA, such as miR‐6087, for diagnosing bladder cancer in the training and validation sets. Furthermore, we found that a combination of 7 miRNA (7‐miRNA panel: miR‐6087, miR‐6724‐5p, miR‐3960, miR‐1343‐5p, miR‐1185‐1‐3p, miR‐6831‐5p and miR‐4695‐5p) could discriminate bladder cancer from non‐cancer and other types of tumors with the highest accuracy (AUC: .97; sensitivity: 95%; specificity: 87%). The diagnostic accuracy was high, regardless of the stage and grade of bladder cancer. Our data demonstrated that the 7‐miRNA panel could be a biomarker for the specific and early detection of bladder cancer.

A miRNA-based diagnostic model predicts resectable lung cancer in humans with high accuracy

“…Once a miRNA was judged to be present, the average signal of the negative control was subtracted from the miRNA signal. Three internal control miRNAs (miR-4463, miR-2861, and miR-1493-p) were used to normalize the microarray signals as described previously [44][45][46][47][48] . The expression levels of these miRNAs in the present dataset were checked by geNorm log2 ranking analysis, and the results showed that these miRNAs were in the top 100 in serum samples from both NCCH and YMC (data shown in Supplementary Table 4), suggesting that these miRNAs are also suitable for normalization in this study.…”

Predictive biomarkers for drug response in bladder cancer

“…In cancer, detection of cancer‐specific genetic alterations in blood could allow early diagnosis of surgically‐resectable cancers . A panel of circulating miRNA in blood was able to discriminate early‐stage bladder cancer from non‐cancer and other types of tumors with the area under the curve of 0.97 . Notably, targetable genetic alterations were successfully detected by sequencing cell‐free DNA in blood from patients with metastatic urothelial cancer, which would allow drug selection targeting the genetic drivers identified in cancer cells without tissue sampling in addition to monitoring of the disease extension .…”

“…66 A panel of circulating miRNA in blood was able to discriminate early-stage bladder cancer from non-cancer and other types of tumors with the area under the curve of 0.97. 67 Notably, targetable genetic alterations were successfully detected by sequencing cell-free DNA in blood from patients with metastatic urothelial cancer, which would allow drug selection targeting the genetic drivers identified in cancer cells without tissue sampling in addition to monitoring of the disease extension. [68][69][70] Circulating tumor cells could also be found in more than half of patients with MIBC, indicating blood sampling combined with deep sequencing would enable molecular subtyping of MIBC without resection of tumors.…”

MiRNAs in Radiotherapy Resistance of Nasopharyngeal Carcinoma

“…They bind to target mRNA molecules through partial or complete complementary sequences or to specific proteins to form miRNA-induced silencing complex and inhibit the translation of target mRNAs [8]. Many previous studies have found that miRNAs regulate the expression of key genes in cell cycle, apoptosis and migration, and affect the proliferation, invasion and metastasis of various tumor cells including nasopharyngeal carcinoma [9][10][11][12][13][14]. Some Ivyspring International Publisher scholars have compared microarray data of miRNA expression profiles in radiotherapy-sensitive and radiation-resistant nasopharyngeal carcinoma cells, identified differentially expressed miRNAs and mRNAs, and constructed a post-transcriptional regulatory network of more than 300 miRNA target gene pairs [11,15].…”

“…Many previous studies have found that miRNAs regulate the expression of key genes in cell cycle, apoptosis and migration, and affect the proliferation, invasion and metastasis of various tumor cells including nasopharyngeal carcinoma [9][10][11][12][13][14]. Some Ivyspring International Publisher scholars have compared microarray data of miRNA expression profiles in radiotherapy-sensitive and radiation-resistant nasopharyngeal carcinoma cells, identified differentially expressed miRNAs and mRNAs, and constructed a post-transcriptional regulatory network of more than 300 miRNA target gene pairs [11,15]. Similar studies have been reported by other scholars to show that miRNAs ectopically expressed in nasopharyngeal carcinoma cells affects the expression of their target genes or proteins, thereby affecting the relevant signaling pathways and thereby participating in radiotherapy for nasopharyngeal carcinoma [16].…”