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BACKGROUND: Circulating microRNAs (miRNAs) prove to be potential non-invasive indicators of cancers. The purpose of this study is to profile serum miRNA expression in breast cancer (BC) patients to find potential biomarkers for BC diagnosis. METHODS: The miRNA expression patterns of serum samples from 216 BC patients and 214 normal control subjects were compared. A four-phase validation was conducted for biomarker identification. In the screening phase, the Exiqon miRNA qPCR panel was employed to select candidates, which were further analyzed by quantitative reverse transcriptase PCR in the following training, testing, and external validation phases. RESULTS: A 12-miRNA (let-7b-5p, miR-106a-5p, miR-19a-3p, miR-19b-3p, miR-20a-5p, miR-223-3p, miR-25-3p, miR-425-5p, miR-451a, miR-92a-3p, miR-93-5p, and miR-16-5p) panel in serum was constructed. The diagnostic performance of the panel was assessed using ROC curve analyses. The area under the curves (AUCs) were 0.952, 0.956, 0.941 and 0.950 for the four separate phases, respectively. Additionally, the expression features of the 12 miRNAs were further explored in 32 pairs of BC tumor and para-tumor tissues, and 32 pairs of serum exosomes samples from patients and healthy subjects. miR-16-5p, miR-106a-5p, miR-25-3p, miR-425-5p, and miR-93-5p were highly overexpressed and let-7b-5p was conversely downregulated in tumor tissues. Excluding miR-20a-5p and miR-223-3p, the 10 other miRNAs were all significantly upregulated in BC serum-derived exosomes. CONCLUSION: A signature consisting of 12 serum miRNAs was identified and showed potential for use in non-invasive diagnosis of BC. [ABSTRACT FROM AUTHOR]

Background: Circulating microRNAs (miRNAs) have become reliable sources of non‐invasive biomarkers for cancer diagnosis. Identification of promising miRNA biomarkers in plasma might benefit a lot to the detection of nasopharyngeal carcinoma (NPC). Methods: The Exiqon miRNA qPCR panel was used in the screening stage to identify candidate miRNAs, which were further verified by quantitative reverse transcription polymerase chain reaction (qRT‐PCR) in the following three stages among plasma samples from 200 NPC patients and 189 healthy donors (as normal controls [NCs]). The identified miRNAs were further explored in tissue specimens (48 NPC vs 32 NCs) and plasma exosomes (32 NPC vs 32 NCs). Survival analyses were ultimately conducted by Cox regression models and Kaplan‐Meier curves using log‐rank tests. Results: We identified a 7‐miRNA signature including let‐7b‐5p, miR‐140‐3p, miR‐144‐3p, miR‐17‐5p, miR‐20a‐5p, miR‐20b‐5p, and miR‐205‐5p in plasma for NPC diagnosis after four‐stage validation. The areas under the receiver operating characteristic curve (AUCs) for the signature were 0.879, 0.884, 0.921, and 0.807 for the training, testing, external validation stage, and the combined three stages, respectively. In NPC tissues, miR‐144‐3p, miR‐17‐5p, miR‐20a‐5p, and miR‐205‐5p were consistently up‐regulated while let‐7b‐5p and miR‐140‐3p were significantly down‐regulated compared to NCs. However, none of the seven identified miRNAs were dysregulated in plasma‐derived exosomes in NPC patients. As to survival analysis, none of the seven miRNAs seemed to be associated with NPC prognosis. Conclusion: We identified a 7‐miRNA signature in plasma as promising non‐invasive biomarkers for NPC detection. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is one of the most common cancers in females. Since early detection can bring prognosis benefit, discovery of novel noninvasive biomarkers for BC diagnosis is in urgent need. In this four‐phase study, we profiled miRNA expression in plasma samples from a total of 257 BC patients and 257 normal controls (NCs). Exiqon miRNA qPCR panel was used to select candidate miRNAs in the screening phase which were further analyzed using qRT‐PCR in the following training, testing and external validation phases. Finally, we identified five plasma miRNAs (let‐7b‐5p, miR‐122‐5p, miR‐146b‐5p, miR‐210‐3p and miR‐215‐5p) whose expression levels were significantly different between BC patients and NCs. A 5‐miRNA panel in plasma with high sensitivity and specificity was then constructed to detect BC. The areas under the receiver‐operating characteristic curves (AUCs) of the panel were 0.683, 0.966, 0.978 for the training, testing and external validation sets, respectively. Expression of the identified miRNAs was further analyzed among 32 pairs of BC tissue and the adjacent normal tissue samples as well as plasma‐derived exosome samples from 32 BC patients vs 32 NCs. Let‐7b‐5p was contrarily down‐regulated in BC tissue. In exosomes samples, only miR‐122‐5p was significantly up‐regulated as in plasma for BC patients. In conclusion, we identified a 5‐miRNA plasma panel (let‐7b‐5p, miR‐122‐5p, miR‐146b‐5p, miR‐210‐3p and miR‐215‐5p) that could serve as a promising biomarker for BC detection. [ABSTRACT FROM AUTHOR]

Abstract: Dysregulated microRNAs (miRNAs) in the plasma of patients with lung squamous cell carcinoma (LSCC) might serve as biomarkers for LSCC diagnosis. The expression of miRNAs was performed using quantitative reverse transcription–polymerase chain reaction (qRT‐PCR) on the basis of Exiqon panels in the initial screening phase including three male LSCC pool samples and one normal control (NC) pool sample (per 10 samples were pooled as one pool sample). After the training (32 LSCC vs. 31 NCs), the testing (55 LSCC vs. 55 NCs), and the external validation (15 LSCC vs. 15 NCs) stages via qRT‐PCR, a four‐miRNA signature (miR‐181a‐5p, miR‐21‐5p, miR‐106a‐5p, and miR‐93‐5p) was identified for LSCC detection. Areas under the receiver operating characteristic (ROC) curve (AUC) of the four‐miRNA panel for the training, the testing, and the external validation phases were 0.795, 0.827, and 0.914, respectively. Then, the four miRNAs were explored in LSCC tissue samples (23 LSCC vs. 23 NCs), and their expression was significantly up‐regulated. However, none of the four miRNAs found significantly up‐regulated in plasma exosomes expect miR‐93‐5p with borderline significance (16 LSCC vs. 16 NCs). In summary, our study established a four‐miRNA peripheral plasma signature, which contributed to diagnosing male LSCC patients in China to a certain degree. [ABSTRACT FROM AUTHOR]

Circulating microRNAs (miRNAs) have been used as promising diagnostic biomarkers for esophageal squamous cell carcinoma (ESCC). We performed miRNA expression profiling using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panels from three ESCC pools and one normal control (NC) pool samples. Using qRT-PCR, identified serum miRNAs were further confirmed in training (32 ESCC vs. 32 NCs) and testing stages (108 ESCC vs. 96 NCs). Consequently, five serum miRNAs (miR-20b-5p, miR-28-3p, miR-192-5p, miR-223-3p, and miR-296-5p) were significantly overexpressed in ESCC compared with NCs. The diagnostic value of the 5-miRNA signature was validated by an external cohort (60 ESCC vs. 60 NCs). The areas under the receiver operating characteristic curve (ROC) of the 5-miRNA signature were 0.753, 0.763, and 0.966 for the training, testing, and the external validation stages, respectively. The expression levels of the miRNAs were also determined in tissues, arterial serum, and exosomes. MiR-20b-5p, miR-28-3p, and miR-192-5p were significantly upregulated in ESCC tissues, while miR-296-5p was overexpressed in ESCC serum exosomes. In conclusion, we identified a 5-miRNA signature in serum for the detection of ESCC. [ABSTRACT FROM AUTHOR]

Abstract Colorectal cancer (CRC) has been one of the most commonly diagnosed cancers in global. The differential expression profiles of microRNAs (miRNAs) in CRC plasma of patients have the potential to serve as a diagnostic biomarker. We conducted a four-stage study to identify the potential plasma miRNAs for CRC detection. In the initial screening phase, Exiqon panel (miRCURY-Ready-to-Use-PCR-Human-panel-I + II-V1.M) including 3 CRC pools and 1 normal controls (NCs) pool were applied to acquire miRNA profiles. In the training stage (30 CRC VS. 30 NCs) and testing stage (79 CRC VS. 76 NCs), quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to conduct candidate miRNA profiles. Then the identified miRNAs were verified in external validation stage (30 CRC VS. 26 NCs). Expression levels of identified miRNAs were assessed in tissue samples (24 pairs) and plasma exosomes (18 CRC VS. 18 NCs). Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic accuracy. Seven miRNAs (miR-103a-3p, miR-127-3p, miR-151a-5p, miR-17-5p, miR-181a-5p, miR-18a-5p and miR-18b-5p) were significantly overexpressed in CRC compared with NCs. Area under the ROC curve of the seven-miRNA signature was 0.762, 0.824 and 0.895 for the training, testing and the external validation stages, respectively. Additionally, miR-103a-3p, miR-127-3p, miR-17-5p and miR-18a-5p were discovered significantly up-regulated in CRC tissues; while miR-17-5p, miR-181a-5p, miR-18a-5p and miR-18b-5p were significantly elevated in CRC plasma exosomes. In conclusion, we established a seven-miRNA signature in the peripheral plasma for CRC detection. Highlights • We investigated plasma miRNA profiles of CRC in a four-stage process and present a seven-miRNA signature in discriminating CRC. • We found that miR-103a-3p, miR-127-3p, miR-17-5p and miR-18a-5p were significantly up-regulated in CRC tissues. • We found that miR-17-5p, miR-181a-5p, miR-18a-5p and miR-18b-5p were significantly elevated in CRC plasma exosomes. • We discovered that plasma miR-26a-5p was only up-regulated in colon cancer patients but not in rectal cancer. • We found none of the seven miRNAs demonstrated significant different expression in patients with stage III + IV compared to those with stage I + II. • We found that no difference of the above seven plasma miRNA between left-sided and right-sided CRC. [ABSTRACT FROM AUTHOR]