WISP2/CCN5 is a prognostic biomarker influenced by tumour purity and fibroblast infiltration in hepatocellular carcinoma
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PROVIDER: PRJNA555588 | ENA |
REPOSITORIES: ENA
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Project description:Background Hepatocellular carcinoma (HCC) is the second leading cause of cancer death worldwide. The dismal outcome is attributable to high frequency of recurrence and metastasis. Therefore, identification of effective biomarkers is a key strategy to inform prognosis and improve survival of HCC patients Methods We analysed expression of WNT-1-induced signalling protein-2 (WISP2) and the prognostic correlation in HCC patients using Oncomine, Kaplan Meier plotter, and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) . We explored the role of WISP2 in HCC using the Cancer Cell Line Encyclopedia (CCLE) and gene microarrays and then assessed the correlation between WISP2 and stromal cells in tumour tissues using the Tumor IMmune Estimation Resource (TIMER). Finally, the role of WISP2 and its relationship with tumour purity and fibroblast infiltration were examined both in vitro and in vivo. Results WISP2 was downregulated in HCC tissues, and high expression of WISP2 was associated with better prognosis in patients with certain clinicopathologic characteristics. Upregulation of WISP2 in HCC was related to inhibition of the malignant phenotype in vitro, but these alterations were not observed in vivo . WISP2 also negatively correlated with tumour purity, and increased infiltration of fibroblasts promoted malignant progression in HCC tissues. The enhanced infiltration ability of fibroblasts was related to upregulated high-mobility group protein 1 (HMGB1) after overexpression of WISP2 in HCC. Conclusions The findings shed light on the anticancer role of WISP2 in HCC, suggest that WISP2 overexpression may serve as a biomarker for better prognosis, and indicate that WISP2 expression is influenced by tumour purity and fibroblast infiltration.
2019-07-20 | GSE134563 | GEO
Project description:BackgroundAccumulating evidence indicates that tumour-infiltrating lymphocytes (TILs) are the primary determinant of survival outcomes in various tumours. Thus, we sought to investigate the TIL distribution and density in gastrointestinal stromal tumours (GISTs) and to develop an immune infiltration (II)-based signature to predict prognosis.MethodsThe expression of 8 immune features in the tumour centre (TC) and tumour margin (TM) and PD-L1 in 435 GIST patients was investigated by immunohistochemistry. Then, a 4-feature-based II-GIST signature integrating the CD3+ TC, CD3+ TM, CD8+ TM and CD45RO+ TM parameters was developed using a LASSO Cox regression model in the training cohort and was validated in two separate validation cohorts.FindingsHigh CD3+ TC, CD3+ TM, CD8+ TC, CD8+ TM, CD45RO+ TM, NKp46+ TM and CD20+ TM correlated with improved survival. Patients with high II-GIST scores have better RFS and OS outcomes than those with low II-GIST scores. Multivariable analyses demonstrated that the II-GIST signature is an independent prognostic factor. The receiver operating characteristic (ROC) curve demonstrated that the prognostic accuracy of the II-GIST signature is superior to that of the NIH risk criteria. Further analysis showed that moderate- and high-risk GIST patients with high II-GIST scores could gain survival benefits from adjuvant imatinib therapy.InterpretationThe novel II-GIST signature accurately predicted the survival outcomes of GIST patients. In addition, the II-GIST signature was a useful predictor of survival benefit from imatinib therapy amongst moderate- and high-risk patients with GIST.FundingThis project was supported by National Natural Science Foundation of China (81702325), Natural Science Foundation of Guangdong Province (2017A030310565), and 3&3 Project of the First Affiliated Hospital of Sun Yat-sen University.
| S-EPMC7322257 | biostudies-literature
Project description:Mouse Human Purity mixing studies
| PRJNA902363 | ENA
Project description:We used human + mouse cell mixtures to demonstrate the purity of PIP-seq single cell RNA-sequencing
2023-01-12 | GSE202911 | GEO
Project description:Although several proteogenomic analyses of high-grade serous ovarian cancer (HGSOC) have been conducted, these analyses are often dominated by tissues with high levels of tumor cell nuclei (purity), despite low purity being associated with worse outcome. We performed deep proteogenomic profiling of bulk tumor (BT) and laser microdissection (LMD) enriched tumor (ET) and stromal (ST) cell populations from 70 HGSOC patient tumors spanning a broad spectrum of purity. We identified a cluster of patients with longer progression free survival associated with increased immune signatures and validated proteins correlating with tumor infiltrating lymphocytes (TILs) in 65 tumors collected from an independent cohort of 12 HGSOC patients, as well as with overall survival in an additional cohort of 126 HGSOC patients. We identified that homologous recombination deficient (HRD) tumors express transcriptomic and proteomic pathways associated with metabolism and oxidative phosphorylation that we validated in independent patient cohorts, including 69 HRD-positive HGSOC tumors. In summary, our proteogenomic analysis provides important new clinically relevant insights into HGSOC tumor cell populations, and have uncovered prognostic proteogenomic alterations correlating with TILs, low tumor purity, as well as expression alterations associated with HRD status and immune infiltration.
2024-03-15 | PXD045417 | Pride
Project description:Hydropsychidae Influenced Microbiomes Metagenome
| PRJNA834817 | ENA
Project description:A novel risk score based on immune-related genes for hepatocellular carcinoma as a reliable prognostic biomarker and correlated with immune infiltration
| PRJNA887382 | ENA
Project description:Triple-negative breast cancer represents approximately 15–20% of all reported breast cancer cases, and is characterized by a shorter survival time and higher mortality rates compared to other breast cancer sub-types. Tumor microenvironment (TME) refers to the internal and external environment of tumor tissue. Increasing evidence indicates that a tumor’s microenvironment is tightly associated with the immunological surveillance and defense during the development of breast cancer. Although oncology studies employing digital dissection methodologies have provided some insight on the biological features of TME, the development of methods to investigate the cellular composition of the tumor microenvironment remain an important research priority. In this study, we extracted whole transcriptome from 30 Triple-negative breast cancer (TNBC) patients and then used bioinformatics approaches to characterize cell type content in tumor tissue compared with para-cancerous tissue. We identified 4 types of enriched immune cells and 6 types of downregulated immune cells in the tumor tissue samples. After comprehensive bioinformatics analyses, we developed an ‘immune infiltration score’ (IIS) to quantitatively model immune cell infiltration in TNBC. To demonstrate the utility of the IIS, we used 2 independent datasets for validation. We found that patients with a higher IIS showing a longer progression-free survival time and significantly better prognosis than those with a lower IIS value. In sum, we explored the immune infiltration landscape in 30 TNBC patients and provided a novel and reliable biomarker IIS to evaluate the progression-free survival and prognosis in the TNBC patients.
2021-10-18 | E-MTAB-10886 | biostudies-arrayexpress
Project description:Glioma represents a serious health burden in terms of morbidity and mortality. The prognostic significance of the lymphoid and myeloid infiltrates in glioma is not clearly determined. Moreover, the characterization of different leukocyte subsets in the tumor microenvironment relies mainly on immunohistochemistry observations, and data about their association with prognosis are contradictory. Here, we performed acomprehensive study of both the tumor-infiltrating and circulating immune compartments of patients with high-grade glioma. We identified prognostic tumor and peripheral immune signatures, which associate increased inflammation, immune infiltration and activation with shorter overall survival in high-grade glioma patients. Importantly, we confirmed our observations by flow cytometry analysis and validated the tumor-signature using the TCGA dataset. In addition, both tumor genotype and grade associated with the degree of glioma immune infiltration. Unlike in the majority of cancers, lymphocyte infiltration at the tumor site is anegative prognostic factor in glioma, suggesting the ambivalent pro-tumorigenic role of immune responses in glioma.
2021-11-16 | GSE188812 | GEO