Human circular RNA hsa_circ_0000231 clinical diagnostic effectiveness as a new tumor marker in gastric cancer.

BACKGROUND: Owing to the subtlety of initial symptoms associated with gastric cancer (GC), the majority of patients are diagnosed at later stages. Given the absence of reliable diagnostic markers, it is imperative to identify novel markers that exhibit high sensitivity and specificity. Circular RNA, a non-coding RNA, plays an important role in tumorigenesis and development and is well expressed in body fluids. AIMS: In this study, we aimed to identify hsa_circ_0000231 as a new biomarker for the diagnosis of GC and to assess its clinical diagnostic value in serum. METHODS AND RESULTS: The stability and correctness of hsa_circ_0000231 was determined by agarose gel electrophoresis, Rnase R assay and Sanger sequencing. Real-time quantitative polymerase chain reaction (qRT-PCR) was designed to discover the expression level of hsa_circ_0000231 and whether it has dynamic serum monitoring capability. The correlation between hsa_circ_0000231 and clinicopathological parameters was analyzed by collecting clinical and pathological data from GC patients. In addition, diagnostic efficacy was assessed by constructing receiver operating characteristic curves (ROC). Hsa_circ_0000231 exhibits a stable and consistently expressed structure. In GC serum, cells, and tissues, it demonstrates reduced expression levels. Elevated expression levels observed postoperatively suggest its potential for dynamic monitoring. Additionally its expression level correlates with TNM staging and neuro/vascular differentiation. The area under ROC curve (AUC) for hsa_circ_0000231 is 0.781, indicating its superior diagnostic value compared to CEA, CA19-9, and CA72-4. The combination of these four indicators enhances diagnostic accuracy, with an AUC of 0.833. CONCLUSIONS: The stable expression of hsa_circ_0000231 in the serum of gastric cancer patients holds promise as a novel biomarker for both the diagnosis and dynamic monitoring of GC.

Cholangiocarcinoma combined with biliary obstruction: an exosomal circRNA signature for diagnosis and early recurrence monitoring.

Cholangiocarcinoma (CCA) is a highly malignant biliary tract cancer with currently suboptimal diagnostic and prognostic approaches. We present a novel system to monitor CCA using exosomal circular RNA (circRNA) via serum and biliary liquid biopsies. A pilot cohort consisting of patients with CCA-induced biliary obstruction (CCA-BO, n = 5) and benign biliary obstruction (BBO, n = 5) was used to identify CCA-derived exosomal circRNAs through microarray analysis. This was followed by a discovery cohort (n = 20) to further reveal a CCA-specific circRNA complex (hsa-circ-0000367, hsa-circ-0021647, and hsa-circ-0000288) in both bile and serum exosomes. In vitro and in vivo studies revealed the three circRNAs as promoters of CCA invasiveness. Diagnostic and prognostic models were established and verified by two independent cohorts (training cohort, n = 184; validation cohort, n = 105). An interpreter-free diagnostic model disclosed the diagnostic power of biliary exosomal circRNA signature (Bile-DS, AUROC = 0.947, RR = 6.05) and serum exosomal circRNA signature (Serum-DS, AUROC = 0.861, RR = 4.04) compared with conventional CA19-9 (AUROC = 0.759, RR = 2.08). A prognostic model of CCA undergoing curative-intent surgery was established by calculating early recurrence score, verified with bile samples (Bile-ERS, C-index=0.783) and serum samples (Serum-ERS, C-index = 0.782). These models, combined with other prognostic factors revealed by COX-PH model, enabled the establishment of nomograms for recurrence monitoring of CCA. Our study demonstrates that the exosomal triple-circRNA panel identified in both bile and serum samples serves as a novel diagnostic and prognostic tool for the clinical management of CCA.

Exosome-transported circ_0061407 and circ_0008103 play a tumour-repressive role and show diagnostic value in non-small-cell lung cancer.

BACKGROUND: Circular RNAs (circRNAs), one of the major contents of exosomes, have been shown to participate in the occurrence and progression of cancers. The role and the diagnostic potential of exosome-transported circRNAs in non-small-cell lung cancer (NSCLC) remain largely unknown. METHODS: The NSCLC-associated exosomal circ_0061407 and circ_0008103 were screened by circRNA microarray. The role of circ_0061407 and circ_0008103 in NSCLC was examined in vitro and in vivo. The encapsulation of the two circRNAs into exosomes and the transport to recipient cells were observed by confocal microscopy. The effects of exosome-transported circ_0061407 and circ_0008103 on recipient cells were investigated using a co-culture device. Bioinformatics analyses were performed to predict the mechanisms by which circ_0061407 and circ_0008103 affected NSCLC. The quantitative polymerase chain reaction was used to quantify the exosome-containing circ_0061407 and circ_0008103 in the serum samples of healthy, pneumonia, benign lung tumours, and NSCLC. The diagnostic efficacy was evaluated using receiver operating characteristic curves. RESULTS: The levels of circ_0061407 and circ_0008103 within exosomes were down-regulated in the serum of patients with NSCLC. The up-regulation of circ_0061407 and circ_0008103 inhibited the proliferation, migration/invasion, cloning formation of NSCLC cells in vitro and inhibited lung tumour growth in vivo. Circ_0061407 and circ_0008103 were observed to be packaged in exosomes and transported to recipient cells, where they inhibited the proliferation, migration/invasion, and cloning formation abilities of the recipient cells. Moreover, circ_0061407 and circ_0008103 might be involved in the progression of NSCLC by interacting with microRNAs and proteins. Additionally, lower serum exosomal circ_0061407 and circ_0008103 levels were associated with advanced pathological staging and distant metastasis. CONCLUSIONS: This study identified two novel exosome-transported circRNAs (circ_0061407 and circ_0008103) associated with NSCLC. These findings may provide additional insights into the development of NSCLC and potential diagnostic biomarkers for NSCLC.

Hsa_Circ_0002762 may be a New Marker for the Gastric Cancer Diagnosis and Prognosis.

BACKGROUND: The global incidence and mortality rate of gastric carcinoma (GC) persists at elevated levels, often manifesting no overt symptoms in its early stages. Hsa_circ_0002762 has been identified as an important modulator in cervical cancer. This study aims to explore its role in the context of GC. METHODS: A quantitative real-time polymerase chain reaction (qPCR) was implemented to assess the expression level of hsa_circ_0002762. The over-expression was confirmed through an examination of 28 cases of gastric cancer and their corresponding adjacent tissues. In addition, plasma samples from 78 healthy individuals, from 45 benign gastritis patients, and from 106 gastric cancer patients were collected, and the diagnostic efficacy was assessed by analyzing the receiver operating characteristic (ROC) curve. Simultaneously, postoperative specimens from 36 GC cases were collected, and a Kaplan-Meier survival analysis curve was used to evaluate the prognosis of GC. RESULTS: The study revealed an up-regulation in the expression of hsa_circ_0002762 in gastric cancer plasma and tissues. The area under the receiver operating characteristic (ROC) curve for serum hsa_circ_0002762 was 0.784 (95% CI: 0.719 - 0.851), indicating a higher diagnostic efficiency compared to CEA (0.687, 95% CI: 0.611 - 0.763) and CA199 (0.699, 95% CI: 0.625 - 0.744). Combining these three biomarkers demonstrated an increased sensitivity in the diagnostic effectiveness. Finally, postoperative dynamic monitoring revealed a practical utility in predicting the clinical prognosis using serum has_circ_0002762. CONCLUSIONS: The findings from our study suggest that hsa_circ_0002762 holds promise as a novel diagnostic and prognostic marker for individuals with GC.

CircRNAs in cancer therapy tolerance.

The rapidly expanding field of circular RNA (circ-RNA) research has opened new avenues in cancer diagnostics and treatment, highlighting the role of serum circRNAs as potential biomarkers for assessing tumor therapy resistance. This review comprehensively compiles existing knowledge regarding the biogenesis, function, and clinical relevance of circRNAs, emphasizing their stability, abundance, and cell type-specific expression profiles, which make them ideal candidates for noninvasive early biomarkers in cancer treatment. We explored the roles of circRNAs in oncogenesis and tumor progression and their complex interactions with patient responses to various cancer treatments, such as chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Through the analysis of data from recent studies and clinical trials, we underscore the prognostic significance of serum circRNAs in predicting therapeutic outcomes, their involvement in resistance mechanisms, and their capacity to inform personalized treatment approaches. Additionally, this review addresses the obstacles inherent in circRNA research, including the need for standardized protocols for circRNA extraction and quantification and the elucidation of the clinical significance of circRNAs. Furthermore, our investigation extends to future prospects, including embedding circRNA profiling into regular clinical workflows and pioneering circRNA-based therapeutic approaches. We underscore the transformative potential of serum circRNAs in enhancing cancer diagnosis, improving the accuracy of therapy tolerance predictions, and ultimately fostering the advent of precision oncology.

The application of plasma circRAD18 in the prediction of gestational diabetes mellitus (GDM) and its adverse effects.

BACKGROUND: In cancer biology, circRAD18 promotes glucose metabolism, potentially indicating its involvement in glucose metabolism-related disorders, such as gestational diabetes mellitus (GDM). The present study investigated the predictive role of circRAD18 in GDM and its potential adverse effects. METHODS: A total of 482 women who intended to get pregnant in short-term were enrolled. For those who successfully conceived, plasma samples were collected and followed up until delivery to monitor the occurrence of GDM and its associated adverse events. The accumulation of circRAD18 in plasma was analyzed using RT-qPCR. GDM-free curves and ROC curves were plotted to assess the predictive value of plasma circRAD18 for GDM. RESULTS: After admitting 482 female patients, 388 of them achieved pregnancy within half a year. During the follow-up period, 52 cases were diagnosed with GDM. Compared to non-GDM group (n = 336), the GDM group (n = 52) had a lower accumulation level of circRAD18 on the day of pregnancy confirmation. In addition, low levels of circRAD18 accumulation on that day distinguished potential GDM patients from non-GDM cases. The 388 cases were divided into high and low circRAD18 level groups (n = 194). GDM-free curve analysis showed that patients in the low circRAD18 level group had a higher incidence of GDM compared to the high level group (43/194 vs. 9/194). A close association was found between low levels of plasma circRAD18 and hypertension, but not premature delivery, intrauterine death, malformation, intrauterine infection, miscarriage, macrosomia or intrauterine distress. CONCLUSION: The reduction in the accumulation of plasma circRAD18 is predictive of GDM and hypertension in pregnant women.

Optical Nanobiosensor Based on Surface-Enhanced Raman Spectroscopy and Catalytic Hairpin Assembly for Early-Stage Lung Cancer Detection via Blood Circular RNA.

Lung cancer has become the leading cause of cancer-related deaths globally. However, early detection of lung cancer remains challenging, resulting in poor outcomes for the patients. Herein, we developed an optical biosensor integrating surface-enhanced Raman spectroscopy (SERS) with a catalyzed hairpin assembly (CHA) to detect circular RNA (circRNA) associated with tumor formation and progression (circSATB2). The signals of the Raman reporter were considerably enhanced by generating abundant SERS "hot spots" with a core-shell nanoprobe and 2D SERS substrate with calibration capabilities. This approach enabled the sensitive (limit of detection: 0.766 fM) and reliable quantitative detection of the target circRNA. Further, we used the developed biosensor to detect the circRNA in human serum samples, revealing that patients with lung cancer had higher circRNA concentrations than healthy subjects. Moreover, we characterized the unique circRNA concentration profiles of the early stages (IA and IB) and subtypes (IA1, IA2, and IA3) of lung cancer. These results demonstrate the potential of the proposed optical sensing nanoplatform as a liquid biopsy and prognostic tool for the early screening of lung cancer.

CircRNAs as Potential Blood Biomarkers and Key Elements in Regulatory Networks in Gastric Cancer.

Gastric cancer (GC) is the fifth most common type of cancer and the third leading cause of cancer death in the world. It is a disease that encompasses a variety of molecular alterations, including in non-coding RNAs such as circular RNAs (circRNAs). In the present study, we investigated hsa_circ_0000211, hsa_circ_0000284, hsa_circ_0000524, hsa_circ_0001136 and hsa_circ_0004771 expression profiles using RT-qPCR in 71 gastric tissue samples from GC patients (tumor and tumor-adjacent samples) and volunteers without cancer. In order to investigate the suitability of circRNAs as minimally invasive biomarkers, we also evaluated their expression profile through RT-qPCR in peripheral blood samples from patients with and without GC (n = 41). We also investigated the predicted interactions between circRNA-miRNA-mRNA and circRNA-RBP using the KEGG and Reactome databases. Overall, our results showed that hsa_circ_0000211, hsa_circ_0000284 and hsa_circ_0004771 presented equivalent expression profiles when analyzed by different methods (RNA-Seq and RT-qPCR) and different types of samples (tissue and blood). Further, functional enrichment results identified important signaling pathways related to GC. Thus, our data support the consideration of circRNAs as new, minimally invasive biomarkers capable of aiding in the diagnosis of GC and with great potential to be applied in clinical practice.

Genome-wide profiling of the expression of serum derived exosomal circRNAs in patients with hepatic alveolar echinococcosis.

The patients with hepatic alveolar echinococcosis is poorly detected due to invasive and slow growth. Thus, early diagnosis of hepatic alveolar echinococcosis is so important for patients. Circular RNAs are crucial types of the non-coding RNA. Recent studies have provided serum-derived exosomal circRNAs as potential biomarkers for detection of various diseases. The clinical importance of exosomal circRNAs in hepatic alveolar echinococcosis have never been explored before. Here, we investigated the serum-derived exosomal circRNAs in the diagnosis of hepatic alveolar echinococcosis. Firstly, High-throughput Sequencing was performed using 9 hepatic alveolar echinococcosis and 9 control samples to detect hepatic alveolar echinococcosis related circRNAs. Afterwards, bioinformatic analyzes were performed to identify differentially expressed circRNAs and pathway analyzes were performed. Finally, validation of the determined circRNAs was performed using RT-PCR. The sequencing data indicated that 59 differentially expressed circRNAs; 31 up-regulated and 28 down-regulated circRNA in hepatic alveolar echinococcosis patients. The top 5 up-regulated and down-regulated circRNAs were selected for validation by RT-qPCR assay. As a result of the verification, circRNAs that were significantly up- and down-regulated showed an expression profile consistent with the results obtained. Importantly, our findings suggested that identified exosomal circRNAs could be a potential biomarker for the detection of hepatic alveolar echinococcosis serum and may help to understand the pathogenesis of hepatic alveolar echinococcosis.

Plasma circN4BP2L2 is a promising novel diagnostic biomarker for epithelial ovarian cancer.

BACKGROUND: Circular RNAs (circRNAs) are more stable than linear RNA molecules, which makes them promising diagnostic biomarkers for diseases. By circRNA-sequencing analysis, we previously found that circN4BP2L2 was significantly decreased in epithelial ovarian cancer (EOC) tissues, and was predictive of disease progression. The aim of this study was to evaluate the diagnostic value of plasma circN4BP2L2 in EOC. METHODS: Three hundred seventy-eight plasma samples were acquired prior to surgery. Samples were obtained from 126 EOC patients, 126 benign ovarian cyst patients, and 126 healthy volunteers. CircN4BP2L2 was assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) were assessed using enzyme-linked immunosorbent assay (ELISA). EOC cells were transfected with small interference RNAs (siRNAs) and cell proliferation, migration, invasion, cell cycle and cell apoptosis were performed to assess the effect of circN4BP2L2 in EOC. Receiver operating curve (ROC), the area under the curve (AUC), sensitivity and specificity were estimated. RESULTS: Plasma circN4BP2L2 was significantly downregulated in EOC patients. Decreased circN4BP2L2 was significantly associated with advanced tumor stage, worse histological grade, lymph node metastasis and distant metastasis in EOC. CircN4BP2L2 inhibited tumor cell migration and invasion in vitro. CircN4BP2L2 could significantly separate EOC from benign (AUC = 0.82, P <  0.01) or normal (AUC = 0.90, P <  0.01) cohort. Early stage EOC vs benign (AUC = 0.81, P <  0.01) or normal (AUC = 0.90, P <  0.01) cohort could also be distinguished by circN4BP2L2. In discrimination between EOC cohort and benign or normal cohort, circN4BP2L2 performed equally well in both pre- and post-menopausal women. The combination of circN4BP2L2, CA125 and HE4 showed high sensitivity and specificity in detecting EOC cases. CONCLUSIONS: Plasma circN4BP2L2 is significantly downregulated in EOC and might serve as a promising novel diagnostic biomarker for EOC patients, especially in early stage EOC cases. CircN4BP2L2 might act as an adjunct to CA125 and HE4 in detecting EOC. Further large-scale studies are warranted to verify our results.

Evaluation of plasma circ_0006282 as a novel diagnostic biomarker in colorectal cancer.

BACKGROUND: Nowadays, non-invasive and rapid detection of cancers through molecular biomarkers has received much attention. Therefore, this study investigated the non-invasive and rapid diagnosis of colorectal cancer through one of the newest biomarkers (circular RNA). METHODS: For this purpose, we collected tumoral, adjacent normal tissue, and plasma samples from 100 colorectal cancer (CRC) patients, 25 postoperative CRC patients, 28 colitis patients, and 108 healthy donors. First Illumina high-throughput (Hi Seq 2000) sequencing was performed to identify known and novel differentially expressed circRNAs in the cancerous and adjacent normal tissues (n = 3). We used quantitative real-time fluorescent polymerase chain reaction (qRT-PCR) to detect the expression level of hsa_circ_0006282 among the different samples. Moreover, inter- and intra-assays were performed to evaluate the potential of hsa_circ_0006282 as being a biomarker. The receiver operating characteristic curve (ROC) was drawn to appraise its diagnostic efficacy, and the sensitivity of this circ RNA was evaluated. RESULTS: Based on RNA-sequencing results circ_0006282, cirs7, circ-0001313, circ_0055625, circ_000984, circ_0055625, circ_0001178, circ_0071589, circ-001569 were upregulated, and circ-ITGA7, circ-CDYL, circITCH, circ_0026344, circ_0000038, circ_0002220, circ_0067480, circIGHV3-20-1, circ_104916, circ_0009361 were downregulated circRNA. The hsa_circ_0006282 was the highest upregulated differentially expressed circRNA. Expression evaluation of this circRNA on different samples showed upregulation in CRC tissues (p < 0.0001) and plasma samples of CRC patients in comparison to healthy controls (p < 0.0001), while the area under the curve (AUC) was 0.831 (95% CI: 0.779-0.883). Expression of hsa_circ_0006282 in CRC patients decreased to normal after surgery (p < 0.0001). Our results showed high specificity and sensitivity of CRC detection when hsa_circ_0006282, carcinoembryonic antigen (CEA), and carbohydrate antigen199 (CA199) are combined. CONCLUSION: Plasma hsa_circ_0006282 can be used as a novel diagnostic and dynamic monitoring biomarker in CRC patients.

New Circulating Circular RNAs with Diagnostic and Prognostic Potential in Advanced Colorectal Cancer.

Circular RNAs (circRNAs) are a group of special endogenous long non-coding RNAs which are highly stable in the circulation, and, thus, more suitable as new biomarkers of colorectal cancer (CRC). The aim of our study was to explore the plasma expression levels of four circRNAs: has_circ_0001445, hsa_circ_0003028, hsa_circ_0007915 and hsa_circ_0008717 in patients with CRC and to evaluate their associations with clinicopathological characteristics and the clinical outcome of the patients. CircRNAs were extracted from patients' plasma obtained prior to chemotherapy. Their expression levels were measured by qPCR and calculated applying the 2-ΔΔCt method. The levels of all four circRNAs were significantly increased in the plasma of CRC patients. At the optimal cut-off values hsa_circ_0001445 and hsa_circ_0007915 in plasma could significantly distinguish between patients with or without metastatic CRC with 92.56% sensitivity and 42.86% specificity, and with 86.07% sensitivity and 57.14% specificity, respectively. The mean overall survival (OS) of patients with high/intermediate expression of hsa_circ_0001445 was 30 months, significantly higher in comparison with the mean OS of the patients with low expression-20 months (log-rank test, p = 0.034). In multivariate Cox regression analysis, the low levels of hsa_circ_0001445 were also associated with shorter survival (HR = 1.59, 95% CI: 1.02-2.47, p = 0.040). A prognostic significance of hsa_circ_0001445 for patients with metastatic CRC was established.

Dysregulated expression of circular RNAs serve as diagnostic and prognostic markers in ovarian and cervical cancer: A PRISMA-compliant systematic review and meta-analysis.

INTRODUCTION: Recent studies have reported a connection between non-coding RNAs such as circular RNAs (circRNAs) and the prognosis of various cancers. However, the mechanism of circRNA in ovarian cancer and cervical cancer has not been consistent. We evaluated the diagnostic and prognostic roles of circRNAs in ovarian and cervical cancer by meta-analysis. METHODS: Pooled hazard ratios with 95% confidence intervals were to estimate overall survival. Diagnostic efficacy was estimated by sensitivity, specificity and area under curve. RESULTS: By searching PubMed, Embase, the Web of Science databases, and other sources, we obtained a total of 22 studies with 2059 patients from Asia population. High expression levels of oncogenic circRNAs were significantly associated with poor prognoses both in ovarian and cervical cancer. However, elevated expression levels of tumor-suppressor circRNAs were linked with favorable survival time in ovarian cancer. As for diagnostic role, the area under the curve value in ovarian cancer and cervical cancer is 0.89 and 0.93, respectively. CONCLUSIONS: CircRNAs have the prospect of becoming a promising biomarker for diagnosis and prognosis of ovarian and cervical cancer. Accordingly, circRNAs might be novel indicators and targets of therapy for ovarian and cervical cancer.

Circular RNAs 0064286 and 0000475: Potential Diagnostic Biomarkers in Hepatocellular Carcinoma.

OBJECTIVE: Hepatocellular carcinoma (HCC) is considered the highest recorded malignancy in Egypt. The shortage of appropriate biomarkers for early detection often results in the late diagnosis of the HCC. Circular RNAs (CircRNAs) are presented as long stranded non-coding RNA that combine covalently to make a sealed circular form which make them very stable. CircRNAs are known to have interpretative role in cancer development and metastasis. AIM: To examine the dysregulation of two new CircRNAs obtained from Circbase database (hsa_circ_0064286 and hsa_circ_0000475) in the serum of HCC patients as predictable diagnostic biomarkers of HCC and their correlation with some liver biochemical parameters. METHODS: Sixty clinically diagnosed HCC Egyptian patients and 25 healthy volunteers were enrolled in the study. Expression levels of the selected CircRNAs was evaluated in subjects' serum. Moreover, correlation with liver biochemical parameters, sensitivity, and specificity of studied CircRNAs were estimated. RESULTS: Both circular RNAs were significantly down regulated in HCC patients, which was negatively correlated with ALP, ALT, AST, AFP, and bilirubin levels. Circ_0064286 showed more sensitivity and specificity (88.3% and 96%, respectively). CONCLUSION: As far as we know, this is the first study that shed light on the expression levels of both circRNAs in Egyptian HCC patients. They may serve as potential biomarkers for HCC diagnosis. Moreover, those circRNAs draw attention as therapeutic targets for HCC through targeting their sponge miRNAs.

Plasma circular RNA hsa_circ_0001821 acts as a novel diagnostic biomarker for malignant tumors.

BACKGROUND: Circular RNAs (circRNAs) can function as key regulators of oncogenic processes. The main purpose of this study was to evaluate the expression of hsa_circ_0001821 in plasma of patients with colorectal cancer (CRC) and other malignant tumors and analyze its correlations with clinical features and diagnostic values. METHODS: In total, 467 plasma samples, including samples from 80 healthy controls, were collected between 2015 and 2019 from patients at the Affiliated People's Hospital of Ningbo University. Plasma levels of hsa_circ_0001821 were analyzed by qRT-PCR. The diagnostic value was performed using receiver operating characteristic (ROC) curve. RESULTS: Plasma hsa_circ_0001821 was increased in CRC patients, and high hsa_circ_0001821 expression predicted advanced stage and unfavorable in overall survival. In addition, this study showed the upregulation of hsa_circ_0001821 in plasma of lung cancer and hepatocellular carcinoma (HCC). ROC curve showed that the region under the loop for the diagnosis of CRC, HCC, and lung cancer was 0.815, 0.692, and 0.792. CONCLUSION: Plasma hsa_circ_0001821 possibly is a novel biological marker for malignant tumors.

Serum Circ-FAF1/Circ-ELP3: A novel potential biomarker for breast cancer diagnosis.

BACKGROUND: Recently, measurement of serum circular RNAs (circRNAs) as a non-invasive tumor marker has been considered more. We designed the present study to investigate the diagnostic efficiency of serum Circ-ELP3 and Circ-FAF1, separately and simultaneously, for diagnosis of patients with breast cancer. METHODS: Seventy-eight female patients diagnosed as primary breast cancer participated in this study. We measured the level of circRNAs in serum specimens of the studied subjects. A receiver operating characteristic (ROC) curve was plotted and the diagnostic efficiency for both circRNAs was determined. RESULTS: Compared to non-cancerous controls, Circ-ELP3 was upregulated in breast cancer patients (p-value = 0.004). On the other hand, serum Circ-FAF1 was seen to be decreased in breast cancer patients than controls (p-value = 0.001). According to ROC curve results, the area under the curve (AUC) for Circ-ELP3 and Circ-FAF1 was 0.733 and 0.787, respectively. Furthermore, the calculated sensitivity and specificity for Circ-ELP3 and Circ-FAF1 were 65, 64% and 77, 74%, respectively. Merging both circRNAs increased the diagnostic efficiency, with a better AUC, sensitivity and specificity values of 0.891, 96 and 62%, respectively. CONCLUSION: Briefly, our results revealed the high diagnostic value for combined circRNAs panel, including Circ-ELP3 and Circ-FAF1 as a non-invasive marker, in detection of breast carcinomas.

Circulating non-coding RNAs as new biomarkers and novel therapeutic targets in colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignant tumors, and a large number of patients are diagnosed and die every year. Due to the lack of appropriate diagnosis, prediction and treatment, early diagnosis rate of CRC is low and the prognosis is poor. Studies have found that abnormally expressed non-coding RNAs (ncRNAs) (including microRNAs (miRNAs), circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs),etc.) play an important regulatory role in the occurrence and development of CRC. Some studies have shown that they are stable in the blood and can be detected repeatedly. They are expected to be non-invasive biomarkers for early diagnosis, prognosis evaluation, and prediction of drug sensitivity of CRC, as well as potential applications in the treatment of CRC.

Hsa_circ_0054633 association of C peptide is related to IL-17 and TNF-α in patients with diabetes mellitus receiving insulin treatment.

BACKGROUND: Chronic inflammation damaged the islet and resulted in dysfunction of T2D. Circular RNA is stable and better for biomarker in many diseases. Here, we aimed to identify potential circular RNA hsa_circ_0054633 that can be a biomarkers for the effects of insulin therapy in T2D. METHODS: In this retrospective case-control study, patients were from Li Huili Hospital, Ningbo, China, from February 10, 2019, to August 15, 2019. We included 47 healthy adults, 46 new-onset T2D with insulin resistance, and 51 patients with insulin therapy. Serum inflammation factors were tested by ELISA assays. We selected hsa_circ_0054633 as a candidate biomarker and measured its concentration in serum by qRT-PCR. The Pearson correlation test was used to evaluate the correlation between this circRNA and clinical variables. RESULTS: Clinical data indicated that serum C peptide was increased in T2D treatment with insulin. Serum hsa_circ_0054633 was decreased in insulin treatment group. Hsa_circ_0054633 was negative correlated with C peptide (r = -0.2841, p = 0.0433,). IL-1 and IL-6, IL-17, and TNF-α were higher in T2D patients and decreased after insulin treatment, only IL-17 and TNF-α showed a positive correlation to hsa_circ_0054633 (r = 0.4825, p < 0.0001, and r = 0.6190, p < 0.0001). The area under ROC curve was 0.7432, 0.5839, and 0.7573 for Hsa_circ_0054633, C peptide, and their combination. CONCLUSION: Hsa_circ_0054633 level was lower in T2D with insulin treatment than untreated and was a negative correlation with C peptide, and positively correlated with IL-17 and TNF-α, suggesting that hsa_circ_0054633 may be a potential early indicator of insulin treatment effect to improve inflammation condition.