Genomic Analysis of diffuse Gastric cancer cells from malignant Ascites
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Project description:Peritoneal carcinomatosis with malignant ascites is associated with dismal prognosis in gastric cancer. Malignant ascites is the most relevant body fluid in which to seek diagnostic biomarkers for peritoneal carcinomatosis. We aimed to identify and validate ascites-derived circulating microRNAs (miRNAs) that are differentially expressed between liver cirrhosis-associated benign ascites (LC-ascites) and gastric cancer-associated malignant ascites (GC-ascites). MiRNA expression levels were investigated in three independent cohorts. Overall, 165 ascites samples (73 LC-ascites and 92 GC-ascites) were obtained from the National Biobank of Korea. Initially, microarrays were used to screen the expression levels of 2,006 miRNAs in the discovery cohort (n = 22). Subsequently, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analyses were used to validate the expression levels of selected miRNAs in the training (n = 70) and validation (n= 73) cohorts. In addition, the levels of carcinoembryonic antigen (CEA), a commonly used tumor marker, were determined in the ascites samples. Expression levels of miR-574-3p, miR-181b-5p, miR-4481, and miR-181d were significantly lower in the GC-ascites samples than in the LC-ascites samples, and miR-181b-5p showed the best diagnostic performance for GC-ascites (area under the curve [AUC] = 0.798 and 0.846 for the training and validation cohorts, respectively). The diagnostic performance of CEA for GC-ascites was improved if CEA and miR-181b-5p were analyzed together (AUC = 0.981 and 0.946 for the training and validation cohorts, respectively). Overall, we identified ascites-derived circulating miRNAs capable of differentiating non-malignant ascites and GC-ascites, and demonstrated that the combined use of miR-181b-5p and CEA produces the optimal diagnostic yield.
2019-02-12 | GSE126399 | GEO
Project description:Gastric cancer is one of the most lethal malignancies with high mortality and gastric cancer-specific biomarker is need due to the lack of specific method for early screening, diagnosis, and prognosis of the patients with gastric cancer. Ascites is known for an important source for conducing biomarker discovery because it contains the secreted proteins from malignant cells, growth factors, and cytokines. In this study, we have conducted a comprehensive proteome study using ascites of patients with inflammatory diseases and gastric cancer. In the discovery stage, we have identified 2761 ascites-specific proteins, where 234 proteins were quantitated using the label free quantitation method, the normalized spectral abundance factor (NSAF); 152 and 82 proteins showed up and down-regulated pattern, respectively. Our ascites proteome can be used as baseline data for the discovery of novel biomarkers of the gastric cancer.
2018-04-16 | PXD002213 | Pride
Project description:Methylation profiling in gastric cancer with malignant ascites.
| PRJNA714888 | ENA
Project description:Ascites-derived circulating microRNAs as potential diagnostic biomarkers of gastric cancer-associated malignant ascites
| PRJNA521772 | ENA
Project description:RNA sequence of gastric cancer with malignant ascites [RNA-seq]
| PRJNA681017 | ENA
Project description:Ascites is a valuable source of cancer biomarkers, because it contains a variety of secreted and shed proteins from cancerous cells. Conversely, most proteomic studies on ascites have focused on ovarian cancer and provided insufficient depth for biomarker discovery. Further, no proteomic analysis of ascites from gastric cancer has been reported. To this end, we profiled the human ascites proteome to obtain a pool of biomarker candidates using comprehensive proteomic strategies. Subsequently, label-free quantitation was performed to compare the abundance of proteins between benign disease and gastric cancer patients.
2018-04-16 | PXD004501 | Pride
Project description:Gastric cancer is one of the leading causes of cancer mortality worldwide, and peritoneal metastasis is a hallmark of incurable advanced gastric cancer. The identification of molecular vulnerability for such conditions is imperative to improve the prognosis of gastric cancer. Here, we comprehensively analysed cancer cells purified from malignant ascitic fluid samples and their corresponding cell lines from 98 patients, through whole-genome sequencing, whole transcriptome sequencing, methylation analyses, and genome-wide enhancer analyses.
2021-05-21 | GSE168999 | GEO
Project description:Gastric cancer is one of the leading causes of cancer mortality worldwide, and peritoneal metastasis is a hallmark of incurable advanced gastric cancer. The identification of molecular vulnerability for such conditions is imperative to improve the prognosis of gastric cancer. Here, we comprehensively analysed cancer cells purified from malignant ascitic fluid samples and their corresponding cell lines from 98 patients, through whole-genome sequencing, whole transcriptome sequencing, methylation analyses, and genome-wide enhancer analyses.
2021-05-21 | GSE162214 | GEO
Project description:To define the cellular characteristics of malignant ascites of advanced gastric cancer patients and search for therapeutic strategies, we applied single cell RNA sequencing to cancer cells and tumor associated macrophages (TAM), present in large numbers in malignant ascites. We analyzed 180 cells from 4 malignant ascites and 1 cerebrospinal fluid metastasis. The results indicate that the anti-inflammatory characteristics of the tumor associated macrophages are concocted by the tumor cells. By constructing reference transcriptomes for M1 and M2 type macrophages, we found a strong non-inflammatory property of macrophages recovered from the malignant ascites of gastric cancer.
2020-12-10 | GSE140182 | GEO
Project description:Gastric cancer is a leading cause of death from cancer globally. Gastric cancer is classified into intestinal, diffuse and indeterminate subtypes based on histology according to the Laurén classification. The intestinal and diffuse subtypes, although different in histology, demographics and outcomes, are still treated in the same fashion. This study was designed to discover proteomic signatures of diffuse and intestinal subtypes. Mass spectrometry-based proteomics using tandem mass tags (TMT)-based multiplexed analysis was used to identify proteins in tumor tissues from patients with diffuse or intestinal gastric cancer with adjacent normal tissue control. A total of 7,804 or 5,166 proteins were identified from intestinal or diffuse subtype, respectively. This quantitative mass spectrometric analysis defined a proteomic signature of differential expression across the two subtypes, which included gremlin1 (GREM1), bcl-2-associated athanogene 2 (BAG2), olfactomedin 4 (OLFM4), thyroid hormone receptor interacting protein 6 (TRIP6) and melanoma-associated antigen 9 (MAGE-A9) proteins. Although GREM1, BAG2, OLFM4, TRIP6 and MAGE-A9 have all been previously implicated in tumor progression and metastasis, they have not been linked to intestinal or diffuse subtypes of gastric cancer. Using immunohistochemical labelling of a tissue microarray comprising of 132 cases of gastric cancer, we validated the proteomic signature obtained by mass spectrometry in the discovery cohort. Our findings should help investigate the pathogenesis of these gastric cancer subtypes and potentially lead to strategies for early diagnosis and treatment.
2022-02-17 | PXD026279 | Pride