Circulating Exosomal miR-17-92 Cluster Serves as a Novel Non-Invasive Diagnostic Marker for Gastric Cancer Patients

Abstract Gastric cancer (GC) is one of the most common malignant tumors with a leading cause of cancer-related mortality worldwide. Exosomal miRNAs are considered as promising non-invasive biomarkers for the diagnosis of malignant tumors. In this study, we aimed to investigate the expression of exosomal miR-17-92 cluster and develop a potential biomarker for the diagnosis of GC. Exosomal RNAs were extracted and the expression profile of miR-17-92 cluster was detected using quantitative polymerase chain reaction (qRT-PCR). The ROC (receiver-operating characteristic) curve and AUC (area under the ROC curve) analysis were used to explore the diagnostic utility of miRNAs. Statistical was used to analyze the expression of serum exosomal miR-17-92 cluster with the clinical pathological parameters of GC patients. The results showed that the expressions of four members of the exosomal miR-17-92 cluster in the serum samples of GC patients were significantly upregulated compared with those of healthy controls. The AUC for serum exosomal miR-17, miR-18, miR-19a and miR-92 was 0.750 (95%CI=0.626-0.874, sensitivity=84.7%, specificity=70.0%), 0.736 (95%CI=0.590-0.881, sensitivity=88.9%, specificity=65.0%), 0.700 (95%CI=0.562-0.838, sensitivity=62.5%, specificity=80.0%), 0.689 (95%CI=0.567-0.811, sensitivity=45.8%, specificity=90.0%), respectively. The AUC for the newly combined panel consisting of miR-17, miR-18, miR-19a and miR-92 was 0.808 (95%CI=0.680-0.937), with sensitivity of 90.3% and specificity of 70.0%, which showed much higher clinical diagnostic value for GC than any of the four alone or any pair. Besides, the AUC for the newly developed panel consisting of the two traditional tumor biomarkers including CEA (carcinoembryonic antigen) and CA19-9 (carbohydrate antigen 19-9) and the four miR-17-92 cluster members was 0.881 (95%CI, 0.765-0.998) with sensitivity of 91.7% and specificity of 90.0%, which showed the greatest powerful clinical diagnostic value for GC. Moreover, the elevated exosomal miR-17-92 expressions were closely correlated with tumor size, tumor depth, lymph node metastasis, distant metastasis and TNM stage of GC patients. In conclusion, our findings revealed that circulating exosomal miR-17-92 cluster may be used as a novel potential non-invasive biomarker to improve the diagnostic efficiency in GC.

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Diagnostic value of plasma HSP90α levels for detection of hepatocellular carcinoma

BMC Cancer ◽

10.1186/s12885-019-6489-0 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Wene Wei ◽

Mengshu Liu ◽

Shufang Ning ◽

Jing Wei ◽

Jianhong Zhong ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Heat Shock Protein 90 ◽

Diagnostic Value ◽

Initial Diagnosis ◽

Hepatic Hemangioma ◽

Diagnostic Efficiency ◽

Roc Curve Analysis ◽

Major Health Problem ◽

Healthy Donors ◽

Potential Biomarker

Abstract Background Hepatocellular carcinoma (HCC) is a major health problem worldwide. However, the popular tumor marker, AFP, lacks sensitivity although its specificity is high. Tissue biopsy is an invasive operation and may increase the risk of needle-track metastases. Heat shock protein 90 (HSP90) is a potential biomarker for tumor diagnosis and prognosis. This study aims to determine whether levels of plasma HSP90α in HCC patients can be used as a cost-effective and simple test for the initial diagnosis of the disease. Methods Plasma samples were collected from 659 HCC patients, 114 secondary hepatic carcinoma (SHC) patients, 28 hepatic hemangioma patients and 230 healthy donors. The levels of HSP90α were measured by ELISA. Results The levels of plasma HSP90α in HCC patients were significantly higher than in healthy donors and in patients with hepatic hemangioma or SHC (144.08 ± 4.98, 46.81 ± 1.11, 61.56 ± 8.20 and 111.96 ± 10.08 ng/mL, respectively; p < 0.05 in all cases). The levels were associated with age (p = 0.001), BCLC stage (p < 0.001), levels of AFP (p < 0.001), tumor size (p < 0.001), tumor number (p < 0.001), PVTT (p < 0.001), EHM (p < 0.001) and Child-Pugh stage in the HCC cohort. In addition, the levels of plasma HSP90α showed an upward trend along with the progression of the BCLC stage. ROC curve analysis showed that compared to AFP (AUC 0.922, 95%CI 0.902–0.938) or HSP90α (AUC 0.836, 95%CI 0.810–0.860), the combination of HSP90α and AFP (AUC0.943, 95%CI 0.925–0.957) significantly improved the diagnostic efficiency for HCC patients. Conclusion The results suggest that plasma Hsp90 α levels can be used as an initial diagnosis for patients with HCC in both rural and cosmopolitan settings.

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Plasma long non-coding RNA HOTAIR as a potential biomarker for gastric cancer

The International Journal of Biological Markers ◽

10.1177/1724600818760244 ◽

2018 ◽

Vol 33 (4) ◽

pp. 528-533 ◽

Cited By ~ 19

Author(s):

Eman T. Elsayed ◽

Perihan E. Salem ◽

Azaa M. Darwish ◽

Haytham M. Fayed

Keyword(s):

Gastric Cancer ◽

Characteristic Curve ◽

Healthy Controls ◽

Non Invasive ◽

Diagnosis And Prognosis ◽

Advanced Tumor ◽

Potential Biomarker ◽

Tumor Stages ◽

Tumorigenesis And Progression ◽

Gastric Cancer Patients

Background: Long non-coding RNAs (lncRNAs) Hox transcript antisense intergenic RNA ( HOTAIR) has been suggested to be implicated in gastric cancer tumorigenesis and progression; however, little is known about the role of the plasma HOTAIR in gastric cancer diagnosis and prognosis. Objective: The current study was aimed at investigating the clinical relevance of plasma long non-coding HOTAIR as a non-invasive diagnostic biomarker in gastric cancer. Methods: Plasma HOTAIR expression was measured in 50 patients with newly diagnosed gastric cancer and 50 age- and sex-matched healthy controls using quantitative reverse transcription polymerase chain reaction. Results: Plasma level of HOTAIR was significantly higher in gastric cancer patients compared with healthy controls ( P < 0.001). By using receiver operating characteristic curve analysis, it was found that plasma HOTAIR could diagnose gastric cancer with 88% sensitivity and 84% specificity. Furthermore, increased HOTAIR expression was associated with advanced tumor stages, higher grades, and metastasis. Conclusion: Plasma HOTAIR might serve as a potential non-invasive biomarker for diagnosis of gastric cancer.

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Comprehensive Assessment of Plasma-Derived circ_0004771 as a Potential Biomarker in Tracking the Progression of Gastric Cancer

10.21203/rs.3.rs-36545/v1 ◽

2020 ◽

Author(s):

Yanhua Xu ◽

Shan Kong ◽

Xinyue Qin ◽

Shaoqing Ju

Keyword(s):

Gastric Cancer ◽

Characteristic Curve ◽

High Specificity ◽

Expression Level ◽

Tumor Biomarker ◽

Diagnostic Efficiency ◽

Diagnostic Efficacy ◽

Potential Biomarker ◽

Diagnostic Values ◽

Fluorescent Polymerase Chain Reaction

Abstract Background: Due to the lack of specific and sensitive detection indicators, most patients with gastric cancer (GC) are already in the advanced stage at the time of diagnosis, resulting in a higher mortality. Therefore, it is urgent to search for effective diagnostic biomarkers with high specificity that can be applied in clinic. Methods: We screened out circ_0004771 through circRNA sequencing performed on three pairs of GC tissues and corresponding paracancerous tissues. Both exonuclease digestion assay, agarose gel electrophoresis (AGE) and sanger sequencing verified the potential of circ_0004771 being a biomarker. Additionally, we established quantitative real-time fluorescent Polymerase Chain Reaction (qRT-PCR) to detect the expression level of circ_0004771 and evaluated the methodology. What’s more, we collected plasma samples from GC patients, precancerous patients and gastritis patients, and we constructed the receiver operating characteristic curve (ROC) to appraise its diagnostic efficacy. Meanwhile, we collected the clinicopathological data of the patients to analyze the relationship between the expression level of circ_0004771 and the pathological parameters of the patients. Results: The expression level of circ_0004771 is up-regulated both in GC tissues and cells compared to normal controls. Circ_0004771 can be served as a promising biomarker because of its stable cyclic structure and longer half-life. The expression level of plasma circ_0004771 can distinguish between GC patients and precancerous patients, GC patients and gastritis patients. The diagnostic efficiency of circ_0004771 is higher than that of CEA and CA199. Higher diagnostic efficiency can be achieved in combination diagnosis. The expression level of plasma circ_0004771 in GC patients decreased after surgery, which can track the recovery condition of patients. Besides, the downstream regulatory forecast indicates that circ_0004771 may act as miRNA sponge to regulate the progression of GC.Conclusion: Plasma circ_0004771 can be served as a less invasive tumor biomarker with high diagnostic values.

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Screening of Potential Biomarkers for Gastric Cancer with Diagnostic Value Using Label-free Global Proteome Analysis

10.1101/2020.03.08.20031930 ◽

2020 ◽

Author(s):

Yongxi Song ◽

Jun Wang ◽

Jingxu Sun ◽

Xiaowan Chen ◽

Jinxin Shi ◽

...

Keyword(s):

Gastric Cancer ◽

Large Scale ◽

Malignant Tumors ◽

Characteristic Curve ◽

Diagnostic Value ◽

Healthy Controls ◽

Label Free ◽

Diagnostic Power ◽

Hub Proteins ◽

Potential Biomarkers

AbstractGastric cancer (GC) is one of the most malignant tumors worldwide. Despite the recent decrease in mortality rates, the prognosis remains poor. Therefore, it is necessary to find novel biomarkers with early diagnostic value for GC. In this study, we present a large-scale proteomic analysis of 30 GC tissues and 30 matched healthy tissues using label-free global proteome profiling. Our results identified 537 differentially expressed proteins, including 280 upregulated and 257 downregulated proteins. The ingenuity pathway analysis (IPA) results indicated that the sirtuin signaling pathway was the most activated pathway in GC tissues whereas oxidative phosphorylation was the most inhibited. Moreover, the most activated molecular function was cellular movement, including tissue invasion by tumor cell lines. Based on IPA results, 15 hub proteins were screened. Using the receiver operating characteristic curve, most of hub proteins showed a high diagnostic power in distinguishing between tumors and healthy controls. A four-protein (ATP5B-ATP5O-NDUFB4-NDUFB8) diagnostic signature was built using a random forest model. The area under the curve (AUC) of this model was 0.996 and 0.886 for the training and testing set, respectively, suggesting that the four-protein signature has a high diagnostic power. This signature was further tested with independent datasets using plasma enzyme-linked immune sorbent assays, resulted in an AUC of 0.778 for distinguishing GC tissues from healthy controls, and using immunohistochemical tissue microarray analysis, resulting in an AUC of 0.805. In conclusion, this study identifies potential biomarkers and improves our understanding of the pathogenesis, providing novel therapeutic targets for GC.

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PIVKA-II serves as a potential biomarker that complements AFP for the diagnosis of hepatocellular carcinoma

BMC Cancer ◽

10.1186/s12885-021-08138-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Honglei Feng ◽

Bole Li ◽

Ze Li ◽

Qian Wei ◽

Li Ren

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Disease ◽

Malignant Tumors ◽

Characteristic Curve ◽

Clinicopathological Characteristics ◽

High Morbidity ◽

Healthy Controls ◽

Diagnostic Efficiency ◽

Potential Biomarker ◽

Benign Liver

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive system and has high morbidity and mortality rates. It is essential to search new biomarkers to improve the accuracy of early HCC diagnosis. Therefore, we evaluated the diagnostic value of prothrombin induced by vitamin K deficiency or antagonist- II (PIVKA-II) as a potential biomarker that complements α-fetoprotein (AFP) in HCC by detecting the serum PIVKA-II levels. Methods Serum PIVKA-II levels were compared in 168 HCC patients, 150 benign liver disease patients and 153 healthy controls to investigate the PIVKA-II potential to be a HCC biomarker. Receiver operating characteristic curve (ROC) analysis was used to evaluate the value of PIVKA-II in the diagnosis of HCC and its complementary role of AFP. The correlation between serum PIVKA-II levels and clinicopathological characteristics was analyzed to study the value of PIVKA-II in assessing HCC progression and prognosis. Finally, the ability of PIVKA-II in assessing the surgical treatment effects of HCC was studied by comparing the pre- and post-operative serum PIVKA-II levels in 89 HCC patients. Results Serum PIVKA-II levels in HCC patients were significantly higher than that in patients with benign liver disease and healthy controls. The PIVKA-II performance in the diagnosing HCC as an individual biomarker was remarkable. The combined detection of PIVKA-II and AFP improved the diagnostic efficiency of HCC. PIVKA-II retained significant diagnosis capabilities for AFP-negative HCC patients. Significant correlations were found between PIVKA-II expression levels and some clinicopathological characteristics, including tumor size, tumor stage, tumor metastasis, differentiation degree and complications. PIVKA-II expression obviously decreased after surgical resection. Conclusions PIVKA-II is a promising serum biomarker for the HCC diagnosis that can be used as a supplement for AFP. The combined diagnosis of the two markers greatly improved the diagnostic efficiency of HCC. The PIVKA-II levels in HCC patients were widely associated with clinicopathological characteristics representing tumor cell dissemination and/or poor prognosis. PIVKA-II can be used to evaluate the curative effects of HCC resection.

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Three plasma-based microRNAs as potent diagnostic biomarkers for endometrial cancer

Cancer Biomarkers ◽

10.3233/cbm-200972 ◽

2021 ◽

pp. 1-12

Author(s):

Xingchen Fan ◽

Minmin Cao ◽

Cheng Liu ◽

Cheng Zhang ◽

Chunyu Li ◽

...

Keyword(s):

Endometrial Cancer ◽

Operating Characteristic ◽

Characteristic Curve ◽

External Validation ◽

Diagnostic Value ◽

Diagnostic Biomarkers ◽

Non Invasive ◽

Polymerase Chain ◽

Public Datasets ◽

Plasma Mirnas

BACKGROUND: MicroRNAs (miRNAs), with noticeable stability and unique expression pattern in plasma of patients with various diseases, are powerful non-invasive biomarkers for cancer detection including endometrial cancer (EC). OBJECTIVE: The objective of this study was to identify promising miRNA biomarkers in plasma to assist the clinical screening of EC. METHODS: A total of 93 EC and 79 normal control (NC) plasma samples were analyzed using Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) in this four-stage experiment. The receiver operating characteristic curve (ROC) analysis was conducted to evaluate the diagnostic value. Additionally, the expression features of the identified miRNAs were further explored in tissues and plasma exosomes samples. RESULTS: The expression of miR-142-3p, miR-146a-5p, and miR-151a-5p was significantly overexpressed in the plasma of EC patients compared with NCs. Areas under the ROC curve of the 3-miRNA signature were 0.729, 0.751, and 0.789 for the training, testing, and external validation phases, respectively. The diagnostic performance of the identified signature proved to be stable in the three public datasets and superior to the other miRNA biomarkers in EC diagnosis. Moreover, the expression of miR-151a-5p was significantly elevated in EC plasma exosomes. CONCLUSIONS: A signature consisting of 3 plasma miRNAs was identified and showed potential for the non-invasive diagnosis of EC.

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Diagnostic value of macrophage inhibitory cytokine 1 as a novel prognostic biomarkers for early gastric cancer screening

10.21203/rs.3.rs-17962/v1 ◽

2020 ◽

Author(s):

Xin Ge ◽

Xiaolei Zhang ◽

Yanling Ma ◽

Shaohua Chen ◽

Zhaowu Chen ◽

...

Keyword(s):

Gastric Cancer ◽

Early Gastric Cancer ◽

Cancer Diagnosis ◽

Early Stage ◽

Precancerous Lesions ◽

Diagnostic Value ◽

Low Grade ◽

Serum Samples ◽

Early Screening ◽

Roc Curve Analysis

Abstract BACKGROUND Early diagnosis is very important to improve the survival rate of patients with gastric cancer, especially in asymptomatic participants. However, low sensitivity of common biomarkers has caused difficulties in early screening of gastric cancer. In this study, we explored whether MIC-1 can improve the detection rate of early gastric cancer.METHODS We screened 8,257 participants based on risk factors such as age, gender, and family history for physical examination including gastroscopy. Participant blood samples were taken for measure MIC-1, CA-199, CA72-4 and PG1/PG2 levels. The diagnostic performance of MIC-1 was assessed and compared with CA-199, CA72-4 and PG1/PG2, and its role in early gastric cancer diagnosis and the assessment of the risk of precancerous lesions have also been studied.RESULTS Based on endoscopic and histopathological findings, 55 participants had gastric cancer, 566 participants had low-grade neoplasia, 2605 participants had chronic gastritis. MIC-1 levels were significantly elevated in gastric cancer serum samples as compared to controls (p<0.001). The sensitivity of serum MIC-1 for gastric cancer diagnosis was much higher than that of CA-199 (49.1% vs. 20.0%) with similar specificities. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MIC-1 had a better performance compared with CA-199, CA72-4 and PG1/PG2 in distinguishing early-stage gastric cancer (AUC: 72.9% vs. 69.5%, 67.5%, 44.0% respectively).CONCLUSIONS Serum MIC-1 is significantly elevated in most patients with early gastric cancer. MIC-1 can serve as a novel diagnostic marker of early gastric cancer and value the risk of gastric cancer.

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Diagnostic Value of MicroRNA 21 in Endometrial Cancer and Benign Lesions and its Differential Expression in Relation to Clinicopathological Parameters

MicroRNA ◽

10.2174/2211536610666210604122816 ◽

2021 ◽

Vol 10 ◽

Author(s):

Amal Bouziyane ◽

Maryame Lamsisi ◽

Hicham Benaguida ◽

Mustapha Benhessou ◽

Mohamed El Kerroumi ◽

...

Keyword(s):

Endometrial Cancer ◽

Characteristic Curve ◽

Myometrial Invasion ◽

Figo Stage ◽

Diagnostic Value ◽

Clinicopathological Parameters ◽

Benign Lesions ◽

Tumor Tissues ◽

Potential Biomarker ◽

Noninvasive Samples

Background: Endometrial cancer is one of the most common malignancies among women worldwide. Although this cancer is often diagnosed at early stages, the need for biomarkers of diagnosis remains a necessity to overcome conventional invasive procedures of diagnosis. Objective: In our study, we aim to investigate the diagnostic value of microRNA-21 in endometrial cancer and its relation to clinicopathological features. Methods: We used RT-qPCR to measure the expression of microRNA-21 in 71 tumor tissues, 53 adjacent tissues, and 54 benign lesions. Results: Our results show that microRNA-21 is a potential biomarker for endometrial cancer with an area under the receiver operating characteristic curve of 0.925 (95% CI = 0.863 - 0.964, P<0.0001). The sensitivity was 84.51% (95% CI = 74.0 - 92.0) and specificity was 86.79% (95% CI = 74.7 - 94.5). For discrimination between benign lesions and controls the AUC was 0,881 with a sensitivity of 100% (95% CI = 93.4 - 100.0) and specificity of 66.04 % (95% CI = 51.7 - 78.5), and for discriminating benign lesions from tumors the AUC was 0,750 with a sensitivity of 54.93% (95% CI = 42.7 - 66.8) and specificity of 90.74% (95% CI = 79.7 - 96.9). We also found that tumors with elevated microRNA-21 expression are of advanced FIGO stage, high histological grades, and have cervical invasion, myometrial invasion and distant metastasis. Conclusion: Our findings support the important role of miR-21 as a biomarker for the diagnosis of endometrial cancer. Further studies on minimally invasive/noninvasive samples such as serum, blood, and urine are necessary to provide a better alternative to current diagnosis methods.

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Decreased circulating clusterin reflects severe liver complications after hepatoportoenterostomy of biliary atresia

Scientific Reports ◽

10.1038/s41598-020-76875-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Wanvisa Udomsinprasert ◽

Yong Poovorawan ◽

Voranush Chongsrisawat ◽

Paisarn Vejchapipat ◽

Sittisak Honsawek

Keyword(s):

Characteristic Curve ◽

Linear Regression Analysis ◽

Diagnostic Value ◽

Enzyme Linked Immunosorbent Assay ◽

Multivariate Linear Regression Analysis ◽

Severe Liver ◽

Non Invasive ◽

Kasai Operation ◽

Poor Outcomes ◽

Extracellular Chaperone

AbstractThis study aimed to determine whether circulating levels of clusterin (CLU), an extracellular chaperone implicated in cholestatic and fibrotic processes, are associated with clinical parameters of post-operative BA patients and could serve as a BA biomarker. Ninety-six BA patients and 56 healthy controls were recruited. Circulating CLU levels were measured using enzyme-linked immunosorbent assay. Circulating CLU levels were significantly reduced in BA patients – especially those with worse outcomes including jaundice, severe liver fibrosis, and late-stage of hepatic dysfunction. Multivariate linear regression analysis revealed that circulating CLU levels were negatively associated with outcome parameters indicating jaundice status, degree of fibrosis, and liver dysfunction, but positively correlated with serum albumin and platelet number of BA patients. Lower circulating CLU levels were considerably associated with poor survival of post-operative BA patients. Receiver-operating characteristic curve analysis demonstrated a diagnostic value of circulating CLU as a non-invasive indicator for poor outcomes of BA patients (AUC = 0.85), with a sensitivity of 81.5% and a specificity of 73.5%. All findings indicate that reduced circulating CLU might reflect poor outcomes of BA patients and have potential as a novel biomarker for the disease severity following Kasai-operation.

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circSMARCA5 Functions as a Diagnostic and Prognostic Biomarker for Gastric Cancer

Disease Markers ◽

10.1155/2019/2473652 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Juan Cai ◽

Zhiqiang Chen ◽

Xueliang Zuo

Keyword(s):

Gastric Cancer ◽

Clinical Significance ◽

Survival Data ◽

Cox Regression ◽

Characteristic Curve ◽

Disease Free Survival ◽

Migration And Invasion ◽

Circular Rnas ◽

Functional Roles ◽

Potential Biomarker

Background. Circular RNAs have been implicated in various malignancies and can function as potential biomarkers for cancers. Reportedly, circSMARCA5 was downregulated in hepatocellular carcinoma and glioblastoma multiforme, but upregulated in prostate cancer. The functional roles and clinical significance of circSMARCA5 still remain unknown in the context of gastric cancer (GC). Methods. Expression levels of circSMARCA5 were detected by qRT-PCR. Clinical data including patient basic information, clinicopathological features, and survival data were obtained. The Kaplan-Meier methods, multivariate Cox regression models, and the receiver operating characteristic curve were used to assess the clinical significance of circSMARCA5 in GC. Cell proliferation assays and transwell assays were performed to elucidate the functional roles of circSMARCA5 in GC. Results. The circSMARCA5 level was decreased in GC tissues and cell lines. The low expression level of circSMARCA5 was correlated to poorer overall survival and disease-free survival. Low circSMARCA5 expression was revealed as an independent unfavorable predictive factor for GC. The results indicated that circSMARCA5 had a moderate ability for discrimination between GC patients and controls with an area under the curve of 0.806. Upregulation of circSMARCA5 dampened the proliferation, migration, and invasion of GC cells, whereas circSMARCA5 knockdown promoted GC progression. Discussion. Our results demonstrated that circSMARCA5 was decreased and exerted tumor-suppressive effects in GC. circSMARCA5 can function as a potential biomarker for GC prognosis and diagnosis.

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