The clinicopathological characteristics, prognosis and immune microenvironment mapping in MSI-H/MMR-D endometrial carcinomas
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PROVIDER: PRJNA796219 | ENA |
REPOSITORIES: ENA
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Project description:Endometrial cancer had a relatively high prevalence of MMR deficiency. MMR-D/MSI-H endometrial cancer patients are suggested to be potential beneficiaries of PD-1/PD-L1 inhibitor therapy. Here, we explored the prognostic value of MSI subtype in endometrial cancer and its correlation with immune environment. Based on expression and clinical data of 78 POLE, 123 MSI and 299 Other EC samples from the TCGA-UCEC project, we found that the MSI tumors were identified more often in early stage, had a lower age, better patient survival, enriched CD8+ T cells, and regulatory T cells and less M2 macrophages and activated dendritic cells than the Other group, and shared a relatively similar expression profile with POLE group by differential analysis. In addition, we established the immune landscape of an MMR-D endometrial cancer tissue using unbiased single-cell RNA-seq analysis of 3371 cells. By immunohistochemistry analysis, we found that the MMR-D tumors showed a higher trend of CD20+ B cells infiltration. Our study might expand our understanding of the role of immune subsets in MSI endometrial carcinomas and provide guidance of immunotherapy for endometrial cancer.
2022-03-09 | GSE193430 | GEO
Project description:Gastric cancers with mismatch repair (MMR) inactivation are characterised by microsatellite instability (MSI). In this study, the transcriptional profile of 38 gastric cancers with and without MSI was analysed. Unsupervised analysis showed that the immune and apoptotic gene networks efficiently discriminated these two cancer types. Hierarchical clustering analysis revealed numerous gene expression changes associated with the MSI phenotype. Amongst these, the p53-responsive genes maspin and 14-3-3 sigma were significantly more expressed in tumours with than without MSI. A tight immunosurveillance coupled with a functional p53 gene response is consistent with the better prognosis of MSI cancers. Frequent silencing of MLH1 and downregulation of MMR target genes, such as MRE11 and MBD4, characterised MSI tumours. The downregulation of SMUG1 was also a typical feature of these tumours. The DNA repair gene expression profile of gastric cancer with MSI is of relevance for therapy response.
2008-12-18 | GSE13911 | GEO
Project description:Gastric cancers with mismatch repair (MMR) inactivation are characterised by microsatellite instability (MSI). In this study, the transcriptional profile of 38 gastric cancers with and without MSI was analysed. Unsupervised analysis showed that the immune and apoptotic gene networks efficiently discriminated these two cancer types. Hierarchical clustering analysis revealed numerous gene expression changes associated with the MSI phenotype. Amongst these, the p53-responsive genes maspin and 14-3-3 sigma were significantly more expressed in tumours with than without MSI. A tight immunosurveillance coupled with a functional p53 gene response is consistent with the better prognosis of MSI cancers. Frequent silencing of MLH1 and downregulation of MMR target genes, such as MRE11 and MBD4, characterised MSI tumours. The downregulation of SMUG1 was also a typical feature of these tumours. The DNA repair gene expression profile of gastric cancer with MSI is of relevance for therapy response. Experiment Overall Design: Genes differentially expressed between MSI and MSS tumours were identified as follows: (i) gene probe sets were pre-selected for being flagged as ‘PRESENT’ in at least 10 tumour samples (21,324 probe sets); (ii) the probe set signal values on the pre-selected probe sets were used to run a t-test between the two types of tumour samples; (iii) the false discovery rate (FDR) method was applied to the t-test calculated p-values to correct for multiple testing and (iv) a false discovery rate <0.05 and a t-test p-value < 0.01 were chosen as threshold criteria to identify the genes differentially expressed in tumours with and without MSI
2009-01-03 | E-GEOD-13911 | biostudies-arrayexpress
Project description:Gene expression was analyzed in terms of canonical molecular changes and clinicopathological features to elucidate alternative or subordinate pathways during colorectal tumorigenesis and tumor growth. Eighty-four sporadic colorectal cancer patients, standardized by tumor location, were consecutively enrolled. Representative molecular changes including APC, TP53, Wnt, RAF, and mismatch repair defect (MMR) were recorded for each sample. Keywords: disease state analysis; sub-type analysis within colorectal cancers 84 samples from colorectal patients were analyzed. Paired tumor and adjacent normal tissues from the same patient were used for hybridization onto custom-made, 21k dual channel cDNA arrays. We prepared a similar number of samples from each of the three tumor locations (ascending 27, descending 29, and rectum 28) and recorded for each sample important molecular changes such as APC, TP53, RAF, WNT, and MMR mutations.
2009-02-28 | E-GEOD-10982 | biostudies-arrayexpress
Project description:Gene expression was analyzed in terms of canonical molecular changes and clinicopathological features to elucidate alternative or subordinate pathways during colorectal tumorigenesis and tumor growth. Eighty-four sporadic colorectal cancer patients, standardized by tumor location, were consecutively enrolled. Representative molecular changes including APC, TP53, Wnt, RAF, and mismatch repair defect (MMR) were recorded for each sample. Keywords: disease state analysis; sub-type analysis within colorectal cancers
2009-03-01 | GSE10982 | GEO
Project description: Not available
| S-EPMC8073383 | biostudies-literature
Project description:Gastric cancer (GC) is the world's third leading cause of cancer mortality. In spite of significant therapeutic improvement, the clinical outcome for patients with advanced GC is poor; thus, the identification and validation of novel targets is extremely important from a clinical point of view. We generated a wide, multi-level platform of GC models, comprising 100 Patient-derived xenografts (PDXs), primary cell lines and organoids. Samples were classified according to their histology, microsatellite stability (MS) and Epstein-Barr virus status, and molecular profile. This PDX platform is the widest in an academic institution and it includes all the GC histologic and molecular types identified by TCGA. PDX histopathological features were consistent with those of patients’ primary tumors and were maintained throughout passages in mice. Factors modulating grafting rate were histology, TNM stage, copy number variation of tyrosine kinases/KRAS genes and MSI status. PDX and PDX-derived cells/organoids demonstrated potential usefulness to study targeted therapy response. Finally, PDX transcriptomic analysis identified a cancer cell intrinsic MSI signature, which was efficiently exported to gastric cancer, allowing the identification -among MSS patients- of a subset of MSI-like tumors with common molecular assets and significant better prognosis. We generated a wide gastric cancer PDX platform, whose exploitation will help identify and validate novel 'druggable' targets and define the best therapeutic strategies. Moreover, transcriptomic analysis of GC PDXs allowed the identification of a cancer cell intrinsic MSI signature, recognizing a subset of MSS patients with MSI transcriptional traits, endowed with better prognosis.
2019-10-15 | GSE128459 | GEO
Project description:Primary outcome(s): Endoscopic and clinicopathological features of depressed-type early colorectal carcinomas
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Project description:This study aims to establish a colorectal cancer cohort, collect clinicopathological information, collect biological samples for multi-omics testing, and perform relevant analysis, to predict the prognosis of colorectal cancer, guide the diagnosis and treatment of colorectal cancer and the formulation of health policies.
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