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

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.

scholarly journals Association and diagnostic value of serum SPINK4 in colorectal cancer

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6679 ◽  
Author(s):  
Mingzhi Xie ◽  
Kezhi Li ◽  
Jilin Li ◽  
Dongcheng Lu ◽  
Bangli Hu
Keyword(s):  
Colorectal Cancer ◽  
Gastric Cancer ◽  
Cancer Patients ◽  
Characteristic Curve ◽  
Disease Free Survival ◽  
Diagnostic Value ◽  
Healthy Controls ◽  
Significant Difference ◽  
Peptidase Inhibitor ◽  
Gastric Cancer Patients

The role of serum serine peptidase inhibitor, Kazal type 4 (SPINK4), in colorectal cancer (CRC) is largely unknown. This study aimed to explore the association and diagnostic value of serum SPINK4 in CRC. A total of 70 preoperative CRC patients, 30 postoperative CRC patients, 30 gastric cancer patients, and 30 healthy controls were enrolled. Using enzyme-linked immunosorbent assays, we found that the serum SPINK4 level was significantly increased in preoperative CRC compared with postoperative CRC patients, gastric cancer patients, and healthy controls (p < 0.05). The serum SPINK4 level was remarkably elevated in colon cancer compared with rectal cancer and was enhanced in the M1 stage compared with the M0 stage (p < 0.05). The area under the receiver operating characteristic curve of serum SPINK4 level in the diagnosis of CRC was 0.9186, with a sensitivity and specificity of 0.886 and 0.900, respectively, and a cut-off value of 2.065. There was no significant difference between high and low expression of serum SPINK4 regarding the overall survival time and disease-free survival (p > 0.05). This study demonstrated that the serum SPINK4 level increased in CRC and was associated with the location and distant metastasis of CRC. It had a high diagnostic value in CRC but was not associated with the survival of CRC patients.

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

2021 ◽  
Author(s):  
Fei Liu ◽  
Ye Han ◽  
Dongbao Li ◽  
Jun Zhou ◽  
Jingjing Xu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Malignant Tumors ◽  
Quantitative Polymerase Chain Reaction ◽  
Characteristic Curve ◽  
Diagnostic Value ◽  
Diagnostic Efficiency ◽  
Roc Curve Analysis ◽  
Non Invasive ◽  
Clinical Diagnostic ◽  
Potential Biomarker

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.

scholarly journals Diagnostic value of circulating tumor DNA as an effective biomarker in cervical cancer: a meta-analysis

2019 ◽  
Author(s):  
Yulan Gu ◽  
Chuandan Wan ◽  
Jiaming Qiu ◽  
Yanhong Cui ◽  
Tingwang Jiang
Keyword(s):  
Cervical Cancer ◽  
Likelihood Ratio ◽  
Large Scale ◽  
Meta Analysis ◽  
Characteristic Curve ◽  
Positive Likelihood Ratio ◽  
Negative Likelihood Ratio ◽  
Diagnostic Value ◽  
Circulating Tumor Dna ◽  
Tumor Dna

AbstractThe applications of liquid biopsy have attracted much attention in biomedical research in recent years. Circulating cell-free DNA (cfDNA) in the serum may serve as a unique tumor marker in various types of cancer. Circulating tumor DNA (ctDNA) is a type of serum cfDNA found in patients with cancer and contains abundant information regarding tumor characteristics, highlighting its potential diagnostic value in the clinical setting. However, the diagnostic value of cfDNA as a biomarker in cervical cancer remains unclear. Here, we performed a meta-analysis to evaluate the applications of ctDNA as a biomarker in cervical cancer. A systematic literature search was performed using PubMed, Embase, and WANFANG MED ONLINE databases up to March 18, 2019. All literature was analyzed using Meta Disc 1.4 and STATA 14.0 software. Diagnostic measures of accuracy of ctDNA in cervical cancer were pooled and investigated. Fifteen studies comprising 1109 patients with cervical cancer met our inclusion criteria and were subjected to analysis. The pooled sensitivity and specificity were 0.52 (95% confidence interval [CI], 0.33–0.71) and 0.97 (95% CI, 0.91–0.99), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 16.0 (95% CI, 5.5–46.4) and 0.50 (95% CI, 0.33–0.75), respectively. The diagnostic odds ratio was 32 (95% CI, 10–108), and the area under the summary receiver operating characteristic curve was 0.92 (95% CI, 0.90– 0.94). There was no significant publication bias observed. In the included studies, ctDNA showed clear diagnostic value for diagnosing and monitoring cervical cancer. Our meta-analysis suggested that detection of human papilloma virus ctDNA in patients with cervical cancer could be used as a noninvasive early dynamic biomarker of tumors, with high specificity and moderate sensitivity. Further large-scale prospective studies are required to validate the factors that may influence the accuracy of cervical cancer diagnosis and monitoring.

scholarly journals Validation of an Epstein-Barr Virus Antibody Risk Stratification Signature for Nasopharyngeal Carcinoma by Use of Multiplex Serology

2020 ◽  
Vol 58 (5) ◽  
Author(s):  
Julia Simon ◽  
Zhiwei Liu ◽  
Nicole Brenner ◽  
Kelly J. Yu ◽  
Wan-Lun Hsu ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Large Scale ◽  
Characteristic Curve ◽  
Diagnostic Value ◽  
Stepwise Logistic Regression ◽  
Igg Antibodies ◽  
Barr Virus ◽  
Epstein Barr ◽  
Multiplex Serology

ABSTRACT Serological testing for nasopharyngeal carcinoma (NPC) has recently been reinvigorated by the implementation of novel Epstein-Barr virus (EBV)-specific IgA and IgG antibodies from a proteome array. Although proteome arrays are well suited for comprehensive antigen selection, they are not applicable for large-scale studies. We adapted a 13-marker EBV antigen signature for NPC risk identified by proteome arrays to multiplex serology to establish an assay for large-scale studies. Taiwanese NPC cases (n = 175) and matched controls (n = 175) were used for assay validation. Spearman’s correlation was calculated, and the diagnostic value of all multiplex markers was assessed independently using the area under the receiver operating characteristic curve (AUC). Two refined signatures were identified using stepwise logistic regression and internally validated with 10-fold cross validation. Array and multiplex serology showed strong correlation for each individual EBV marker, as well as for a 13-marker combined model on continuous data. Two refined signatures with either four (LF2 and BGLF2 IgG, LF2 and BMRF1 IgA) or two (LF2 and BGLF2 IgG) antibodies on dichotomous data were identified as the most parsimonious set of serological markers able to distinguish NPC cases from controls with AUCs of 0.992 (95% confidence interval [CI], 0.983 to 1.000) and 0.984 (95% CI, 0.971 to 0.997), respectively. Neither differed significantly from the 13-marker model (AUC, 0.992; 95% CI, 0.982 to 1.000). All models were internally validated. Multiplex serology successfully validated the original EBV proteome microarray data. Two refined signatures of four and two antibodies were capable of detecting NPC with 99.2% and 98.4% accuracy.

scholarly journals Serum CA242: a biomarker for diagnosis, progression, and metastasis in multiple tumors

2020 ◽  
Author(s):  
Kaicheng Shen ◽  
Xiangquan Qin ◽  
Xingxing Su ◽  
Yishi Yang ◽  
Hongqian Wang ◽  
...  
Keyword(s):  
Digestive Tract ◽  
Malignant Tumors ◽  
Clinical Stage ◽  
Clinical Information ◽  
Serum Levels ◽  
Diagnostic Value ◽  
Neoplastic Disease ◽  
Healthy Controls ◽  
Different Types ◽  
Multiple Metastases

Abstract Background CA242 is a classic biomarker used for diagnosing digestive tract tumors, especially pancreatic cancer. However, CA242 serum levels in some tumor patients and what might influence these levels remain unknown or uncertain. This study aimed to reveal the pancancer landscape of serum CA242 levels and identify some influencing factors. Methods In the current study, serum CA242 levels and clinical information, including clinical stage and metastatic status, were collected from 37,493 patients with 35 different types of neoplastic disease, and CA242 values were also obtained for 880 healthy controls. Results Serum CA242 levels in patients with one of 21 different cancers were significantly higher than those in healthy controls and had diagnostic value in 9 tumors (AUC > 0.7, P < 0.05); serum CA242 levels were increased across all malignant digestive tract tumors. Compared to patients without metastasis, cancer patients with one of 15 kinds of cancer with lymph node metastasis and distant metastasis showed elevated CA242 levels. Moreover, CA242 was helpful in distinguishing the clinical stage and metastatic status in 6 cancers. In addition, the presence of multiple metastases and liver metastasis might result in increased CA242 levels. Conclusions Overall, CA242 can not only serve as a diagnostic biomarker for malignant tumors in the digestive system but also predict the progression, stage, and metastasis of many other tumors that have not received clinical attention.

Serum aberrant expression of miR-24-3p and its diagnostic value in Alzheimer’s disease

2021 ◽  
Author(s):  
Lina Liu ◽  
Luran Liu ◽  
Yunting Lu ◽  
Tianyuan Zhang ◽  
Wenting Zhao
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Receiver Operating Characteristic Curve ◽  
Receiver Operating Characteristic ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Diagnostic Value ◽  
Healthy Controls ◽  
Operating Characteristic Curve ◽  
Receiver Operating

Aim: This study aimed to evaluate the effect of miR-24-3p in Alzheimer’s disease (AD). Materials & methods: A total of 198 participants were recruited in this study, including 104 AD patients and 94 healthy controls. Expression of miR-24-3p was detected using quantitative real-time PCR. Receiver-operating characteristic curve was used to assess the diagnostic value of miR-24-3p. In vitro AD model was established to evaluate the effect of miR-24-3p. The downstream target was detected by luciferase reporter gene assay. Results: Expression of miR-24-3p showed 1.6-fold increase in AD group compared with healthy controls, and a negative correlation of miR-24-3p with mini-mental state examination score was obtained. Receiver-operating characteristic curve showed satisfactory diagnostic accuracy. Downregulation of miR-24-3p promoted cell proliferation and inhibited cell apoptosis. KLF8 is a target gene of miR-24-3p. Conclusion: MiR-24-3p has a certain value in the diagnosis of AD and may be a potential biomarker.

scholarly journals Serum Small Proline-Rich Protein 2A (SPRR2A) Is a Noninvasive Biomarker in Gastric Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Xiaoming Xu ◽  
Shumei Wei ◽  
Yueming Chen ◽  
Daojun Yu ◽  
Xianjun Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Diagnostic Value ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Serum Samples ◽  
Node Metastasis ◽  
Median Serum ◽  
Before And After ◽  
Noninvasive Biomarker ◽  
Colorectal Cancer Patients

Objective. Since early diagnosis is very important for treating gastric cancer (GC), we aimed to detect serum small proline-rich protein2A (SPRR2A) to verify its diagnostic value for GC patients. Methods. Serum samples were collected from 200 patients with GC, 100 patients with gastritis, 40 patients with rectal cancer (RC), 50 patients with colon cancer (CC), and 100 healthy controls. An enzyme-linked immunosorbent assay (ELISA) detection kit was applied to measure serum SPRR2A concentration. The correlations between serum SPRR2A and carcinoembryonic antigen (CEA), clinical pathological parameters of GC, and receiver operating characteristic (ROC) curve were also analyzed. Results. The median serum SPRR2A concentration in GC patients was significantly higher than those in healthy controls and gastritis or colorectal cancer patients (P<0.001). Serum SPRR2A concentration at a cut-off value of 80.7 pg/ml yielded an AUC of 0.851, with 75.7% sensitivity and 74.5% specificity for discriminating GC patients from healthy people. The AUC for the serum SPRR2A concentration combined with the CEA concentration was 0.876, with 79.7% sensitivity and 78.7% specificity. Similarly, serum SPRR2A discriminated GC patients from gastritis patients with an AUC of 0.820, with 90.5% sensitivity and 61.7% specificity. The AUC for the serum SPRR2A concentration combined with the CEA concentration was 0.848, with 87.8% sensitivity and 68.1% specificity. The serum SPRR2A levels in GC patients were associated with lymph node metastasis and the tumor-node-metastasis (TNM) stage (P<0.05). There was an obvious difference in serum SPRR2A expression between GC patients before and after surgery (P<0.0001). Conclusion. These results suggest that serum SPRR2A can be used as an effective marker for GC.

scholarly journals Plasma Metabolomics Analysis Based on GC-MS in Infertile Males with Kidney-Yang Deficiency Syndrome

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Piao Zheng ◽  
Yun Wang ◽  
Hongmei Lu ◽  
Xinyi Zhou ◽  
Tao Tang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Male Infertility ◽  
Metabolic Pathways ◽  
Characteristic Curve ◽  
Deficiency Syndrome ◽  
Gas Chromatography Mass Spectrometry ◽  
Healthy Controls ◽  
Chinese Medicine Syndrome ◽  
Kidney Yang Deficiency ◽  
Potential Biomarkers

Introduction. Chinese medicine syndrome diagnosis is the key requisite in the treatment of male infertility with traditional Chinese medicine (TCM). Kidney-Yang deficiency syndrome (KYDS) is the critical Chinese medicine syndrome of male infertility. To explore the modernized mechanisms of KYDS in male infertility, this study aims to investigate the metabolomics of males with KYDS. Methods. The gas chromatography-mass spectrometry method was applied to analyze the plasma samples of 67 infertile males with KYDS compared with 55 age-matched healthy controls. The chemometric methods including principal component and partial least squares-discriminate analyses were employed to identify the potential biochemical patterns. With the help of the variable importance for the projection and receiver operating characteristic curve analyses, the potential biomarkers were extracted to define the clinical utility. Simultaneously the high-quality KEGG metabolic pathways database was used to identify the related metabolic pathways. Results. The metabolomics profiles of infertile males with KYDS including 10 potential biomarkers and six metabolic pathways were identified. They precisely distinguished infertile males with KYDS from healthy controls. Conclusions. These potential biomarkers and pathways suggest the substantial basis of infertile males with KYDS. The metabolomics profiles highlight the modernized mechanisms of infertile males with KYDS.

scholarly journals Using Serological Proteome Analysis to Identify and Evaluate Anti-GRP78 Autoantibody as Biomarker in the Detection of Gastric Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Jiejie Qin ◽  
Qian Yang ◽  
Hua Ye ◽  
Keyan Wang ◽  
Meng Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Large Scale ◽  
Test Group ◽  
Proteome Analysis ◽  
Diagnostic Value ◽  
Validation Group ◽  
Roc Curve Analysis ◽  
Normal Individuals ◽  
And Gender ◽  
Sensitivity Specificity

The serological biomarkers as noninvasive tests are the most promising way for diagnosing gastric cancer (GC). Serological proteome analysis (SERPA) has been used to identify tumor-associated antigens (TAAs) and the corresponding autoantibodies in many studies. To explore the relationship between gastric cancer development and serum autoantibody anti-GRP78 response found by the method of SERPA with the GC cell line AGS, we included two cohorts (133 GC and 133 normal individuals in test group; 300 GC and 300 normal individuals in validation group) of patients with newly diagnosed GC for verification. All GC and normal controls were matched by age and gender. The autoantibody levels of the sera in two cohorts were measured by immunoassay. Finally, the results showed that 78-kDa glucose-regulated protein (GRP78) was identified in GC by SERPA and the level of anti-GRP78 antibody in GC was higher than that in normal individuals in the two cohorts. Receiver operating characteristic (ROC) curve analysis showed similar diagnostic value of anti-GRP78 antibody in test group (AUC: 0.718) and validation group (AUC: 0.666) to identify GC patients from normal individuals. The AUCs of anti-GRP78 autoantibody in the diagnosis of GC patients with different clinical characteristic ranged from 0.676 to 0.773 in test group and ranged from 0.645 to 0.707 in validation group. In conclusion, autoantibody against GRP78 might be a potential diagnostic biomarker. Further large-scale studies will be needed to validate and improve its performance of the sensitivity, specificity, and AUC value in distinguishing GC from other diseases.

Sign in / Sign up

Export Citation Format

Share Document