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Circulating Proteins as Diagnostic Markers in Gastric Cancer.

ABSTRACT: Gastric cancer (GC) is a highly malignant disease affecting humans worldwide and has a poor prognosis. Most GC cases are detected at advanced stages due to the cancer lacking early detectable symptoms. Therefore, there is great interest in improving early diagnosis by implementing targeted prevention strategies. Markers are necessary for early detection and to guide clinicians to the best personalized treatment. The current semi-invasive endoscopic methods to detect GC are invasive, costly, and time-consuming. Recent advances in proteomics technologies have enabled the screening of many samples and the detection of novel biomarkers and disease-related signature signaling networks. These biomarkers include circulating proteins from different fluids (e.g., plasma, serum, urine, and saliva) and extracellular vesicles. We review relevant published studies on circulating protein biomarkers in GC and detail their application as potential biomarkers for GC diagnosis. Identifying highly sensitive and highly specific diagnostic markers for GC may improve patient survival rates and contribute to advancing precision/personalized medicine.

SUBMITTER: Repetto O

PROVIDER: S-EPMC10706891 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Circulating Proteins as Diagnostic Markers in Gastric Cancer.

Repetto Ombretta O Vettori Roberto R Steffan Agostino A Cannizzaro Renato R De Re Valli V

International journal of molecular sciences 20231129 23

Gastric cancer (GC) is a highly malignant disease affecting humans worldwide and has a poor prognosis. Most GC cases are detected at advanced stages due to the cancer lacking early detectable symptoms. Therefore, there is great interest in improving early diagnosis by implementing targeted prevention strategies. Markers are necessary for early detection and to guide clinicians to the best personalized treatment. The current semi-invasive endoscopic methods to detect GC are invasive, costly, and ...[more]

PMID: 38069253

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Project description:Background: Gastric cancer (GC) remains the third leading cause of cancer death worldwide due to the absence of sensitive and specific biomarkers for its early detection. 5-hydroxymethylcytosine (5hmC)-enriched gene profiles and regions show tissue-specific and tumor specific, and cell-free DNA (cfDNA) 5hmC modification feature sequencing provides a robust tool for gastric cancer detection.Methods: A matched case‒control study design with 50 gastric cancer patients and 50 controls was performed to sequence the 5hmC modification of cfDNA. Significantly differential 5hmC modification genes were identified to construct a gastric cancer diagnostic model. The data set from Gene Expression Omnibus consisted of 61 gastric cancer patients, 90 healthy individuals and 22 benign gastric disease controls was used as an external testing set to test the robustness of the diagnostic model. Results: The vast majority of 5hmC peaks were distributed in the gene body, accounting for more than 90% of the total 5hmC peaks in both the GC and control groups. The diagnostic model was developed based on five different 5hmC modification genes, FBXL7, PDE3A, TPO, SNTG2 and SXBP5. The model could clearly distinguish gastric cancer patients from controls in the training (AUC=0.95, sensitivity=88.6%, specificity=94.3%), validation (AUC=0.87, sensitivity=73.3%, specificity=93.3%) and testing (AUC=0.90, sensitivity=81.9%, specificity=90.2%) sets. The predicted risk scores of the controls were significantly lower than those of GC patients in our own data (P<0.001) or GEO external testing data (P<0.001), but no significant difference was observed between different TNM stage groups (P=0.09 and 0.66). Furthermore, the risk scores of healthy and benign gastric disease controls in the testing set were also not different (P=0.10). Conclusions: The characteristics of 5hmC in cfDNA are specific to GC patients, and the diagnostic model constructed by the 5hmC features of five genes could effectively identify GC patients.

Project description:AimThe study was designed to assess the possibility of using circulating miRNAs (serum miRNAs) as diagnostic biomarkers in colorectal cancer (CRC) and to identify their possibility as candidates for targeted therapy.MethodsThe study involved two sample sets: 1- a training set which included 90 patients with colorectal related disease (30 with CRC, 18 with inflammatory bowel disease (IBD), 18 with colonic polyps (CP) and 24 with different colonic symptoms but without any colonoscopic abnormality who were enrolled as control group) and 2- a validation set which included 100 CRC patients. Serum miRNAs were extracted from all subjects to assess the expression profiles for the following miRNAs (miR-17, miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-146a, miR-223, miR-24, miR-454, miR-183, miR-135a, miR- 135b and miR- 92a) using the custom miScript miRNA PCR-based sybergreen array. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of the studied miRNAs for colorectal cancer diagnosis.ResultsData analysis of miRNA from the training set showed that; compared to control group, only miR-19b was significantly up-regulated in patients with IBD group (fold change = 5.24, p = 0.016), whereas in patients with colonic polyps, miR-18a was significantly up-regulated (fold change = 3.49, p-value = 0.018). On the other hand, miR-17, miR-19a, miR-20a and miR-223 were significantly up-regulated (fold change = 2.35, 3.07, 2.38 and 10.35; respectively and p-value = 0.02, 0.015, 0.017 and 0.016; respectively in CRC patients. However, the validation set showed that only miR-223 was significantly up-regulated in CRC patients (fold change = 4.06, p-value = 0.04).ConclusionAberrant miRNA expressions are highly involved in the cascade of colorectal carcinogenesis. We have found that (miR-17, miR-19a, miR-20a and miR-223) could be used as diagnostic biomarkers for CRC. On the other hand, miR-19b and miR-18a could be used as diagnostic biomarkers for CP and IBD respectively.

Project description:BACKGROUND: MicroRNAs are aberrantly expressed and correlate with tumourigenesis and the progression of solid tumours. The miR-200 family determines the epithelial phenotype of cancer cells and regulates invasiveness and migration. Thus, we hypothesised that the quantitative detection of the miR-200 family as epithelial-specific microRNAs in the blood could be a useful clinical biomarker for gastric cancer (GC). METHODS: We initially validated the expression levels of miR-200a, 200b, 200c and 141 in GC cell lines (n?=?2) and blood from healthy controls (n?=?19) using real-time quantitative reverse transcription PCR (qRT-PCR). The microarray expression profiles of the miR-200 family in 160 paired samples of non-tumour gastric mucosae and GC were downloaded through ArrayExpress and analysed. MiR-200c was selected for clinical validation. The qRT-PCR prospective assessment of miR-200c was performed using 67 blood samples (52 stage I-IV GC patients and 15 controls); the area under the receiver operating characteristic curve (AUC-ROC) was estimated. The Kaplan-Meier and Breslow-Wilcoxon tests were used to assess the correlation of miR-200c with overall and progression-free survival (OS and PFS). Multivariate analyses were performed using the Cox model. RESULTS: The miR-200c blood expression levels in GC patients were significantly higher than in normal controls (p?=?0.018). The AUC-ROC was 0.715 (p?=?0.012). The sensitivity, specificity and accuracy rates of 65.4%, 100% and 73.1%, respectively, were observed. The levels of miR-200c in the blood above the cutoff defined by the ROC curve was found in 17.6% of stage I-II GC patients, 20.6% of stage III patients and 67.7% of stage IV patients (p?<?0.001). The miR-200c expression levels were not associated with clinical or pathological characteristics or recent surgical procedures. There was a correlation (p?=?0.016) with the number of lymph node metastases and the increased expression levels of miR-200c in blood were significantly associated with a poor OS (median OS, 9 vs 24?months; p?=?0.016) and PFS (median PFS, 4 vs 11?months; p?=?0.044). Multivariate analyses confirmed that the upregulation of miR-200c in the blood was associated with OS (HR?=?2.24; p?=?0.028) and PFS (HR?=?2.27; p?=?0.028), independent of clinical covariates. CONCLUSIONS: These data suggest that increased miR-200c levels are detected in the blood of gastric cancer patients. MiR-200c has the potential to be a predictor of progression and survival.

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Circulating Proteins as Diagnostic Markers in Gastric Cancer.

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Circulating Proteins as Diagnostic Markers in Gastric Cancer.

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