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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).

2014-10-12 | E-GEOD-51565 | biostudies-arrayexpress

Single Nuclei RNA Sequencing of Uterine Serous Carcinoma

Project description:Single Nuclei RNA Sequencing of Uterine Serous Carcinoma

| PRJNA1082692 | ENA

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

2014-10-12 | GSE51565 | GEO

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

miRNA profiling in high-grade serous ovarian carcinoma

Project description:In this study, we performed miRNA profiles analysis of high-grade serous ovarian carcinoma compared to normal fallopian tube fimbria using microarray (Exiqon, Denmark) to evaluate their potential role in the pathogenesis of uterine leiomyoma. miRNA profiling analysis of the 10 samples including 5 high-grade serous ovarian carcinomas and 5 normal fallopian tube fimbria.

2014-11-14 | E-GEOD-61485 | biostudies-arrayexpress

Expression data from embryonic Plk3 WT and KO animals

Project description:These data investigate the transcriptomic differences in the whole retinas of mice resulting from loss of Polo-like Kinase 3 (Plk3) at embryonic day (E)16.

2016-04-20 | GSE75381 | GEO

Expression data from postnatal Plk3 WT and KO animals

Project description:These data investigate the transcriptomic differences in the whole retinas of mice resulting from loss of Polo-like Kinase 3 (Plk3) over various stages of development, including adulthood, postnatal day (P)7, and P0.

2016-04-20 | GSE75279 | GEO

Single Nuclei RNA Sequencing of Uterine Serous Carcinoma

Project description:Significant racial disparities exist between Black and White patients with uterine serous carcinoma (USC). While the reasons for these disparities are unclear, but several studies have demonstrated significantly distinct rates of driver mutations between racial groups, including TP53. However, limited research has investigated the transcriptional differences of the tumors between these groups, or the composition of the tumor microenvironment (TME) between these groups. Here, we report the findings from the first single nuclei RNA-sequencing experiment conducted on USC tumors. We find that there are significant differences between the tumors of Black and White patients. Tumors exhibited differential expression of specific genes associated with aggressiveness, such as PAX8, and axon guidance and synaptic signaling pathways in Black and White patients. We also demonstrated that differences in T cell and macrophage populations exist between benign and tumor tissues in the TME of USC, as well as between racial groups. Furthermore, we investigated the connection between PAX8 overexpression and immunosuppression in USC through regulation of several cytokines and chemokines. Notably, we show for the first time that PAX8 activity can influence macrophage gene expression and protein secretion. These studies provide a detailed understanding of USC and a basis for using racial information in USC treatment decisions.

2024-09-13 | GSE260683 | GEO

Retinal transcriptomes of Plk3-deficient animals

Project description:Retinal transcriptomes of Plk3-deficient animals

| PRJNA304025 | ENA