A prognostic hypoxia gene signature with low heterogeneity within the dominant tumour lesion in prostate cancer patients.
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PROVIDER: PRJNA739745 | ENA |
REPOSITORIES: ENA
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Project description:Background: Hypoxia gene signatures measured in a biopsy are promising biomarkers in prostate cancer. We determined the ability of a previously developed signature to correctly classify tumours as more or less hypoxic and investigated how intratumour heterogeneity affected its biomarker performance. Methods: The 32-gene signature was determined from gene expression data of 141 biopsies from the dominant (index) lesion of 94 patients treated with prostatectomy. Hypoxic fraction was measured by pimonidazole immunostaining of whole-mount and biopsy sections and used as reference standard for hypoxia. Results: The signature was correlated with hypoxic fraction in whole-mount sections, and the parameters showed almost the same association with tumour aggressiveness. Gene- and pimonidazole-based classification of patients differed considerably. However, the signature had low intratumour heterogeneity compared to hypoxic fraction in biopsies and showed prognostic significance in three independent cohorts. Conclusion: The biopsy-based 32-gene signature from the index lesion reflects hypoxia-related aggressiveness in prostate cancer.
2022-04-01 | GSE178631 | GEO
Project description:BackgroundGene signatures measured in a biopsy have been proposed as hypoxia biomarkers in prostate cancer. We assessed a previously developed signature, and aimed to determine its relationship to hypoxia and its heterogeneity within the dominant (index) lesion of prostate cancer.MethodsThe 32-gene signature was assessed from gene expression data of 141 biopsies from the index lesion of 94 patients treated with prostatectomy. A gene score calculated from the expression levels was applied in the analyses. Hypoxic fraction from pimonidazole immunostained whole-mount and biopsy sections was used as reference standard for hypoxia.ResultsThe gene score was correlated with pimonidazole-defined hypoxic fraction in whole-mount sections, and the two parameters showed almost equal association with clinical markers of tumour aggressiveness. Based on the gene score, incorrect classification according to hypoxic fraction in whole-mount sections was seen in one third of the patients. The incorrect classifications were apparently not due to intra-tumour heterogeneity, since the score had low heterogeneity compared to pimonidazole-defined hypoxic fraction in biopsies. The score showed prognostic significance in uni-and multivariate analysis in independent cohorts.ConclusionsOur signature from the index lesion reflects tumour hypoxia and predicts prognosis in prostate cancer, independent of intra-tumour heterogeneity in pimonidazole-defined hypoxia.
| S-EPMC9296675 | biostudies-literature
Project description:Liver Cancer Evolution - Lesion segregation
| PRJEB37808 | ENA
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:Bearded lizard lesion investigation
| PRJEB25832 | ENA
Project description:OBJECTIVE:To demonstrate the feasibility of an 8-Gy focal radiation boost to a dominant intraprostatic lesion (DIL), identified using multiparametric MRI (mpMRI), and to assess the potential outcome compared with a uniform 74-Gy prostate dose. METHODS:The DIL location was predicted in 23 patients using a histopathologically verified model combining diffusion-weighted imaging, dynamic contrast-enhanced imaging, T2 maps and three-dimensional MR spectroscopic imaging. The DIL defined prior to neoadjuvant hormone downregulation was firstly registered to MRI-acquired post-hormone therapy and subsequently to CT radiotherapy scans. Intensity-modulated radiotherapy (IMRT) treatment was planned for an 8-Gy focal boost with 74-Gy dose to the remaining prostate. Areas under the dose-volume histograms (DVHs) for prostate, bladder and rectum, the tumour control probability (TCP) and normal tissue complication probabilities (NTCPs) were compared with those of the uniform 74-Gy IMRT plan. RESULTS:Deliverable IMRT plans were feasible for all patients with identifiable DILs (20/23). Areas under the DVHs were increased for the prostate (75.1?±?0.6 vs 72.7?±?0.3?Gy; p?<?0.001) and decreased for the rectum (38.2?±?2.5 vs 43.5?±?2.5?Gy; p?<?0.001) and the bladder (29.1?±?9.0 vs 36.9?±?9.3?Gy; p?<?0.001) for the boosted plan. The prostate TCP was increased (80.1?±?1.3 vs 75.3?±?0.9?Gy; p?<?0.001) and rectal NTCP lowered (3.84?±?3.65 vs 9.70?±?5.68?Gy; p?=?0.04) in the boosted plan. The bladder NTCP was negligible for both plans. CONCLUSION:Delivery of a focal boost to an mpMRI-defined DIL is feasible, and significant increases in TCP and therapeutic ratio were found. ADVANCES IN KNOWLEDGE:The delivery of a focal boost to an mpMRI-defined DIL demonstrates statistically significant increases in TCP and therapeutic ratio.
| S-EPMC4075537 | biostudies-literature
Project description:WISP2/CCN5 is a prognostic biomarker influenced by tumour purity and fibroblast infiltration in hepatocellular carcinoma
| PRJNA555588 | ENA
Project description:Gastric cancer is one of the leading causes of cancer mortality worldwide. We compared transcriptomic profiles of advanced gastric cancer with different tumour-stroma-scores to identify the prognostic significance of tumour-stroma-score in advanced gastric cancer.
2021-11-29 | GSE179252 | GEO
Project description:Tumours progress despite being infiltrated by effector T cells. Tumour necrosis is associated with poor survival in a variety of cancers. Here, we report that that necrosis causes release of an intracellular ion, potassium, into the extracellular fluid of human and mouse tumours. Surprisingly, elevated extracellular potassium ([K+]e) was sufficient to profoundly suppress mouse and human T cell anti-tumour function. Elevations in [K+]e acted to acutely impair T cell receptor (TCR) dependent Akt-mTOR phosphorylation and effector function. Potassium mediated suppression of Akt-mTOR signalling and T cell effector function required intact activity of PP2A, a serine/threonine phosphatase. The suppressive effect mediated by elevated [K+]e required a T cell-intrinsic increase in intracellular potassium ([K+]i) and was independent of changes in plasma membrane potential (Vm). Finally, ionic reprogramming of tumour-specific T cells via over-expression of the voltage-gated potassium channel Kv1.3 lowered [K+]i and improved effector functions in vitro and in vivo, with this gain of function being dependent on intact channel function. Consequently, Kv1.3 T cell expression enhanced tumour clearance and the survival of melanoma-bearing mice. These results uncover a previously undescribed ionic checkpoint against T cell function within tumours and identify new strategies for cancer immunotherapy.
2016-08-13 | GSE84996 | GEO
Project description:Ovarian carcinoma has the highest mortality rate among gynecological malignancies. In this project, we investigated the hypothesis that molecular markers are able to predict outcome of ovarian cancer independently of classical clinical predictors, and that these molecular markers can be validated using independent data sets. We applied a semi-supervised method for prediction of patient survival. Microarrays from a cohort of 80 ovarian carcinomas (TOC cohort) were used for the development of a predictive model, which was then evaluated in an entirely independent cohort of 118 carcinomas (Duke cohort). A 300 gene ovarian prognostic index (OPI) was generated and validated in a leave-one-out approach in the TOC cohort (Kaplan-Meier analysis, p=0.0087). In a second validation step the prognostic power of the OPI was confirmed in an independent data set (Duke cohort, p=0.0063). In multivariate analysis, the OPI was independent of the postoperative residual tumour, the main clinico-pathological prognostic parameter with an adjusted hazard ratio of 6.4 (TOC cohort, CI 1.8 – 23.5, p=0.0049) and 1.9 (Duke cohort, CI 1.2 – 3.0, p=0.0068). We constructed a combined score of molecular data (OPI) and clinical parameters (residual tumour), which was able to define patient groups with highly significant differences in survival. The integrated analysis of gene expression data as well as residual tumour can be used for optimised assessment of prognosis. As traditional treatment options are limited, this analysis may be able to optimise clinical management and to identify those patients that would be candidates for new therapeutic strategies. Keywords: disease state analysis RNA from 80 frozen ovarian cancer samples was analysed with oligonucleotide microarrays
2009-02-09 | E-GEOD-14764 | biostudies-arrayexpress