Diagnostic, Therapeutic, and Prognostic Value of the Thrombospondin Family in Gastric Cancer.
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ABSTRACT:
SUBMITTER: Lu Y
PROVIDER: S-EPMC8113821 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThrombospondins (THBSs) are glycoproteins expressed in the extracellular matrix (ECM) and have critical roles in tumor development and metastasis. However, the diverse expression patterns and prognostic roles of distinct THBS genes in gastric cancer have not been fully elucidated. In the current study, we aimed to investigate the expression patterns of THBSs in gastric cancer (GC) and determine whether they are prognostic markers for this malignancy.MethodsmRNA expression status and genetic mutations of THBS family members were performed by using ONCOMINE, UCSC Xena browser, GEPIA, and cBioPortal databases. Prognostic values and function enrichment analysis of the members were assessed via Kaplan-Meier plotter and Metascape.Resultswe found that the mRNA expression of THBS1, THBS2, THBS4, and COMP were higher in patients with GC tissues than those in normal gastric mucosa and there was no difference in the mRNA expression of THBS3 between GC and normal tissue. Survival analysis revealed that mRNA levels of THBSs were strongly related to worse OS in GC patients (P<0.05). Overexpression of THBSs indicated poor OS in stage III/IV GC and high expression of THBS1, THBS3, THBS4, and COMP were related to worse OS in stage II GC.ConclusionsBioinformatics analysis revealed a better understanding the value of THBS family members in GC and suggest that THBSs might serve as potential prognostic biomarkers for GC.
| S-EPMC8107582 | biostudies-literature
Project description:MiRNAs have been widely reported to be involved in the occurrence and development of cancers. So far, some studies have revealed that miR-338-5p has the functions of tumorigenesis and tumor suppression. However, the role of miR-338-5p in the pathogenesis, progression and treatment of gastric cancer (GC) has not been reported. MiRNAs microarray analysis showed for the first time that miR-338-5p was significantly lower-expression in cisplin-resistant GC cells SGC7901/DDP, and cell viability assay and flow cytometry confirmed that overexpression of miR-338-5p could significantly increase cisplatin-sensitivity of SGC7901/DDP and BGC823 cells. Subsequently, we found that the expression of miR-338-5p in postoperative cancer tissues of GC patients was also significantly lower than the corresponding paracancer tissues. The expression of miR-338-5p in peripheral blood serum of GC patients is generally lower than that of healthy people. Moreover, the low expression of miR-338-5p in the cancer tissues and serum of GC patients was closely associated with larger tumor volume, lymph node metastasis, later stage, and even poorer survival, which was confirmed by close 5-year cases follow-up. ZEB2, as a predictive target of miR-338-5p, its expression was negatively regulated by miR-338-5p and can promote cisplatin-resistance in SGC7901/DDP and BGC823 cells. The expression of ZEB2 in cisplatin-resistant SGC7901/DDP cells and GC tissues were significantly higher than SGC7901 cells and paracancer tissues, respectively. Moreover, the expression of ZEB2 in tumor tissues was negatively correlated with miR-338-5p in tumor tissues and peripheral blood serum of GC patients, and the abnormally high expression of ZEB2 in prospective case studies is positively related with more serious clinical pathology and worse survival. More meaningfully, in a retrospective case study, we found that high ZEB2 expression predicts worse clinical efficacy of platinum chemotherapy. Thus, miR-338-5p-ZEB2 axis have novel diagnostic, therapeutic predictive, and prognostic value in GC patients.
| S-EPMC8518007 | biostudies-literature
Project description:Background: Tissue inhibitor of metalloproteinases (TIMP) gene family, including TIMP1, TIMP2, TIMP3 and TIMP4, was found to be correlated with serval cancers. Still the diagnostic and prognostic study of it in gastric cancer (GC) have few reports. Methods and materials: In this study, the gene expression and clinical data were acquired from the Cancer Gene Atlas (TCGA), function enrichment was used by several databases for verifying known function. Operating characteristic (ROC) curves with area under the curve (AUC) used to assess diagnostic value. Survival analysis and joint-effects survival analysis was performed by the Kaplan-Meier curve. The results were adjusted by cox-regression model. Nomogram is used to directly predict the survival rate for individual GC patient. The potential mechanism for diagnostic and prognostic value was assessed by gene set enrichment analysis (GSEA). Further functions of gene were verified by cell proliferation, migration and invasion assays in human gastric cancer cell line. Results: TIMP1 was expressed in GC tissue was higher than normal gastric tissue. TIMP3 and TIMP4 have expressed in normal gastric tissue were higher than GC tissue. TIMP1, TIMP3 and TIMP4 have potential diagnostic value (AUC=0.842, 0.729, 0.786 respectively; all P<0.01). Low expression of TIMP2 and TIMP3 associated with favorable overall survival (all P<0.05). TIMP2 and TIMP3, which had significantly affection of prognosis were found having some function such as tRNA processing, cell cycle pathway ncRNA processing. The silencing of TIMP3 could inhibit the migration and invasion of gastric cancer cell. Conclusion: We analyzed the TIMP gene family in GC, and the prognostic and diagnostic value. TIMP1 and TIMP2 could be used as diagnostic biomarkers in GC. TIMP2 and TIMP3 could be used as potential biomarkers for GC's prognosis.
| S-EPMC8176236 | biostudies-literature
Project description:Colorectal cancer (CRC) ranks as the second leading cause of cancer-related mortality globally and is the third most prevalent cancer. The effective treatment of CRC is challenged by tumor drug resistance, underscoring the urgent need for novel therapeutic strategies. It is well recognized that epigenetic modifications, particularly DNA methylation, significantly contribute to the initiation and advancement of CRC. Tumors frequently exhibit hypermethylation of specific gene promoters alongside a general hypomethylation of genomic DNA. In normal tissues, gene promoters, particularly those of tumor suppressor genes, are typically unmethylated, whereas they are often hypermethylated in cancerous tissues. Previous studies have identified the methylation status of the CpG island within the SLC30A10 gene as a reliable biomarker for CRC. Notably, a hypermethylated phenotype is inversely correlated with SLC30A10 expression. However, the precise functional implications of SLC30A10 suppression in the context of CRC progression remain to be elucidated.). The investigation of molecular pathways involved in metal metabolism in CRC has not been conducted previously at the transcriptomic level. Furthermore, the relationship between the mutational characteristics of tumors—such as individual mutations, mutational burden, and microsatellite instability—and the activity of genes related to metal metabolic pathways has not been explored. This project aims to be the first to examine the antitumor potential of modulating the transport systems for manganese and zinc ions in CRC. The molecular function of SLC30A10 is to export zinc (Zn) and manganese (Mn) ions from the cell. Additionally, SLC30A10 plays a crucial role in mitigating Mn-induced cytotoxicity and facilitates Zn transport to early endosomes while promoting endosomal recirculation to avert Zn toxicity. Our findings indicate that overexpression of SLC30A10 is correlated with the knockout of its functional antagonist, SLC39A14 in the HuTu80 and HCT-15 cell lines.
2024-09-15 | GSE276849 | GEO
Project description:Background The type IV collagen alpha chain (COL4A) family is a major component of the basement membrane (BM) that has recently been found to be involved in tumor angiogenesis and progression. However, the expression levels and the exact roles of distinct COL4A family members in gastric cancer (GC) have not been completely understood. Methods Here, the expression levels of COL4As in GC and normal gastric tissues were calculated by using TCGA datasets and the predicted prognostic values by the GEPIA tool. Furthermore, the cBioPortal and Metascape tools were integrated to analyze the genetic alterations, correlations and potential functions of COL4As, and their frequently altered neighboring genes in GC. Results Notably, the expression levels of COL4A1/2/4 in GC were higher to those in normal gastric tissues, while the expression levels of COL4A3/5/6 were lower in GC than normal. Survival analysis revealed that lower expression levels of COL4A1/5 led to higher overall survival (OS) rate. Multivariate analysis using the Cox proportional-hazards model indicated that age, gender, pathological grade, metastasis and COL4A5 expression, are independent prognostic factors for OS. However, TNM stage, lymph node metastasis, Lauren’s classification, COL4A1-4 and COL4A6 were associated with poor OS but not independent prognostic factors. Function-enriched analysis of COL4As and their frequently altered neighboring genes was involved in tumor proliferation and metastasis in GC. Conclusions These results implied that COL4A1/2 were potential therapeutic targets for GC. COL4A3/4/6 might have an impact on gastric carcinogenesis and subsequent progression, whereas COL4A5 was an independent prognostic marker for GC.
| S-EPMC8799138 | biostudies-literature
Project description:Peripheral blood lymphocyte subsets have been reported to be useful as prognostic and/or diagnostic markers for patients with cancer. However, the clinical value of peripheral blood lymphocyte subsets in gastric cancer (GC) has remained elusive. In the present study, peripheral CD3+, CD4+ and CD8+ T lymphocytes, B cells (CD19+), regulatory T cells (Tregs; CD4+CD25+CD127-) and natural killer (NK) cells (CD3-CDl6+CD56+) were detected by flow cytometry in 122 patients with GC, 80 healthy donors (HDs) and 80 patients with gastric ulcer (GU). NK cells (CD56+) were detected by immunohistochemical (IHC) analysis in 20 GC and three GU tissue samples. A receiver-operating characteristic (ROC) curve was used to determine the threshold of the peripheral NK cell level and survival analysis was performed to assess its prognostic value in patients with GC. The results indicated that the peripheral NK cell proportion in patients with GC (18.77%) was significantly higher than that in the HD (12.19%) and GU (12.74%) groups. IHC analysis suggested that the NK level in GC tumor samples was correlated with that in paired serum samples. ROC curve analysis indicated that the peripheral NK cell level (15.16%) was able to effectively identify patients with GC, a diagnostic sensitivity of 75.41% and a specificity of 77.45% were determined. Multivariate logistic regression analysis revealed that the peripheral NK cell level was independently associated with the T stage and survival analysis demonstrated that high levels of peripheral NK cells were associated with poor prognosis of patients with GC. In conclusion, the peripheral NK cell level may be a diagnostic and prognostic marker for patients with GC.
| S-EPMC7444348 | biostudies-literature
Project description:BackgroundThe role of miR-200c in gastric cancer remains controversial. This study is aimed at clarifying the diagnostic and prognostic value of miR-200c in gastric cancer through a meta-analysis.MethodsA comprehensive literature search of PubMed, Embase, and Ovid library databases was conducted. The studies included were those conducted before December 2017. The sensitivity and specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under curve (AUC) were used to estimate the diagnostic value of miR-200c. Meanwhile, the pooled hazard ratio (HR) was used to estimate the prognostic value of miR-200c.ResultsFor the diagnostic value of miR-200c, six studies that included 202 patients with gastric cancer and 250 normal controls were analyzed. The sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.74, 0.66, 2.20, 0.40, 5.34, and 0.75, respectively. Subgroup analysis showed no significant difference in the type of the sample, method for testing miR-200c, and ethnicity among the patients. Meanwhile, for the prognostic value of miR-200c, seven studies comprising 935 patients with gastric cancer were analyzed. The pooled results showed that miR-200c expression was associated with overall survival (HR = 2.19) and disease-free survival (HR = 1.73), but not with progression-free survival (HR = 1.64) in patients with gastric cancer. There was no publication bias across the studies.ConclusionsBoth serum and tissue miR-200c have moderate diagnostic accuracy in gastric cancer. miR-200c could also be used as a valuable indicator for predicting the prognosis of gastric cancer patients.
| S-EPMC6476052 | biostudies-literature
Project description:BackgroundCirculating tumor DNA (ctDNA) has offered a minimally invasive approach for detection and measurement of gastric cancer (GC). However, its diagnostic and prognostic value in gastric cancer still remains unclear.ResultsA total of 16 studies comprising 1193 GC patients met our inclusion criteria. The pooled sensitivity and specificity were 0.62 (95% confidence intervals (CI) 0.59-0.65) and 0.95 (95% CI 0.93-0.96), respectively. The AUSROC (area under SROC) curve was 0.94 (95% CI 0.89-0.98). The results showed that the presence of certain ctDNA markers was associated with larger tumor size (OR: 0.26, 95% CI 0.11-0.61, p = 0.002), TNM stage (I + II/III + IV, OR: 0.11, 95% CI 0.07-0.17, p = 0.000), as well as H. pylori infection. (H.p negative/H.p positive, OR: 0.57, 95% CI 0.36-0.91, p = 0.018). Moreover, there was also a significant association between the presence of ctDNA and worse overall survival (HR 1.77, 95% CI 1.38-2.28, p < 0.001), as well as disease-free survival (HR 4.36, 95% CI 3.08-6.16, p < 0.001).Materials and methodsPubmed, Embase, Cochrane Library and Web of Science databases were searched for relating literature published up until November 30, 2016. Diagnostic accuracy variables were pooled by the Meta-Disc software. Engauge Digitizer and Stata software were applied for prognostic data extraction and analysis.ConclusionsOur meta-analysis indicates the detection of certain ctDNA targets is significantly associated with poor prognosis of GC patients, with high specificity and relatively moderate sensitivity.
| S-EPMC5351635 | biostudies-literature
Project description:BackgroundWe investigated the expression of two αv integrins, αvβ3 and αvβ5, in gastric cancer (GC) by testing the following hypotheses: that these molecules are expressed in GC; that they are implicated in GC biology; that they help to distinguish between the two major histological subtypes of GC, according to Laurén; and that they are prognostically relevant.MethodsFormalin-fixed and paraffin-embedded tissue samples from 482 GC samples were stained immunohistochemically using rabbit monoclonal antibodies directed against αvβ3 (EM22703) and αvβ5 (EM09902). Immunostaining of tumor, stroma, and endothelial cells was evaluated separately by the quantity and intensity, generating an immunoreactivity score. The immunoreactivity score of both antibodies was correlated with clinicopathology data and patient survival.ResultsEach integrin was expressed in at least one tumor component in all GCs. Both were expressed significantly more often in the intestinal phenotype according to Laurén. Moreover, patients who grouped as "positive" for expression of αvβ3 on endothelial cells, and patients with an intestinal type GC, grouped as "negative" for expression of αvβ5 on stroma cells, had significantly longer survival. The expression of αvβ5 on stroma cells was confirmed to be an independent prognostic factor of intestinal-type GC.ConclusionThe expression of αvβ3 and αvβ5 in at least one tumor component in all GC samples is an interesting new result that should form a basis for further investigations; for example, regarding selective integrin antagonists and the value of αvβ3 and αvβ5 as putative prognostic biomarkers. Moreover, both markers might be helpful in the routine classification of GC subtypes.
| S-EPMC4572058 | biostudies-literature
Project description:Previous studies have demonstrated that members of the brain-expressed X-linked (BEX) family participate in a wide range of biological functions in normal and tumor tissues. However, their role and clinical significance in lung adenocarcinoma (LUAD) remains unclear. The present study investigated The Cancer Genome Atlas data and revealed that the BEX family was downregulated in LUAD tissues compared with adjacent non-cancerous tissues. Additionally, analysis of LUAD cohorts from the Oncomine database revealed similar results. Furthermore, the expression of BEX members was significantly decreased in several LUAD cell lines compared with normal lung epithelial cells . The aforementioned data mining and results suggested that the BEX family may be involved in the development of LUAD. Furthermore, receiver operating characteristic curve analysis revealed that BEX members exhibited high sensitivity and specificity for the diagnosis of patients with LUAD. The low expression levels of BEX1, BEX4 and BEX5 were associated with certain pathologic features, particularly in advanced LUAD. Survival analysis demonstrated that BEX members, particularly BEX4, were involved in the prognosis of patients with LUAD at early and late clinical stages. The results obtained in the current study suggested that BEX members may serve as potential tumor biomarkers for the diagnosis and prognosis of patients with LUAD.
| S-EPMC6781490 | biostudies-other