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PLK3 amplification and tumor immune microenvironment of metastatic tumors are linked to adjuvant treatment outcomes in uterine serous cancer

ABSTRACT: PLK3 amplification and tumor immune microenvironment of metastatic tumors are linked to adjuvant treatment outcomes in uterine serous cancer

PROVIDER: PRJNA844091 | ENA |

REPOSITORIES: ENA

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PLK3 amplification and tumor immune microenvironment of metastatic tumors are linked to adjuvant treatment outcomes in uterine serous cancer

Project description:Uterine serous carcinoma (USC), an aggressive variant of endometrial cancer representing approximately 10% of endometrial cancer diagnoses, accounts for ~39% of endometrial cancer-related deaths. We examined the role of genomic alterations in advanced-stage USC associated with outcome using paired primary-metastatic tumors (n=29) treated with adjuvant platinum and taxane chemotherapy. Comparative genomic analysis of paired primary-metastatic patient tumors included whole exome sequencing and targeted gene expression. Both PLK3 amplification and the tumor immune microenvironment (TIME) in metastatic tumors were linked to time-to-recurrence (TTR) risk without any such association observed with primary tumors. TP53 loss was significantly more frequent in metastatic tumors of platinum-resistant versus platinum-sensitive patient and was also associated with increased TTR and mortality risk. Increased levels of chr1 breakpoints in USC metastatic versus primary tumors co-occur with PLK3 amplification. PLK3 and the TIME are potential targets for improving outcomes in USC adjuvant therapy.

2022-06-01 | GSE205209 | GEO

Comparative DNA methylome analysis of endometrioid adenocarcinoma, uterine papillary serous carcinoma, and normal endometrium

Project description:Classically, there are two types of endometrial cancer, endometrioid adenocarcinoma (EAC), or Type I; and uterine papillary serous carcinoma (UPSC), or Type II. These two types of cancers exhibit distinct DNA methylation levels in promoters of many genes. In EAC, many tumor suppressor genes were silenced due to DNA hypermethylation at their promoter region. However, promoters of many of these genes remained unmethylated in UPSC. Here, we described complete DNA methylome maps of endometrioid adenocarcinoma, uterine papillary serous carcinoma, and normal endometrium, by applying a combined strategy of methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylation-sensitive restriction enzyme sequencing (MRE-seq). We took a complementary and orthogonal approach to identify DNA methylation changes unique to the two endometrial cancer subtypes in an unbiased fashion. We generated complete DNA methylome maps for endometrioid adenocarcinoma (EAC, three samples), uterine papillary serous carcinomas (UPSC, three samples), and normal endometrium (pooled samples) by integrating data from methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylation-sensitive restriction enzyme sequencing (MRE-seq).

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Comparative DNA methylome analysis of endometrioid adenocarcinoma, uterine papillary serous carcinoma, and normal endometrium

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Mapping three-dimensional intratumor proteomic heterogeneity in uterine serous carcinoma by multiregion microsampling

Project description:Uterine serous carcinoma (USC) represents only a small proportion of all uterine cancer cases, but patients with this aggressive subtype typically have high rates of chemotherapy resistance, disease recurrence, and constitute a disproportionately high percentage of the deaths. Improving the clinical management of USC is predicated by better characterization of the tumor microenvironment (TME) and the molecular features driving disease pathology. To improve our understanding of intratumoral heterogeneity (ITH) within the USC TME, we investigated proteome and transcriptome alterations in spatially resolved laser microdissection (LMD) enriched cellular subpopulations from nine USC patient tumor tissue specimens. LMD enriched samples were analyzed via liquid chromatography-tandem mass spectrometry (LC-MS/MS), reverse phase protein microarray (RPPA), and targeted RNA-sequencing (RNA-seq).

2024-01-24 | PXD044197 | Pride

Microarray Analysis Reveals Distinct Gene Expression Profiles Among Different Tumor Histology, Stage and Disease Outcomes in Endometrial Adenocarcinoma

Project description:The goal of this study was to identify differentially expressed genes (DEG) between early vs. late stage endometrioid adenocarcinoma (EAC) and uterine serous carcinoma (USC), as well as between disease outcomes in each of the two histological subtypes. Gene expression profiles of 20 cancer samples were analyzed (EAC =10, USC =10) using the human genome wide illumina bead microarrays carrying 48,000 genes.

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miRNA profiling in high-grade serous ovarian carcinoma

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Project description:Adjuvant-induced human monocyte secretome profiles reveal adjuvant- and age-specific protein signatures.

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