Molecular Determinants of Post-Mastectomy Breast Cancer Recurrence
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PROVIDER: PRJNA490741 | ENA |
REPOSITORIES: ENA
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Project description:Molecular Determinants of Post-Mastectomy Breast Cancer Recurrence
2018-09-20 | PRJEB28702 | EVA
Project description:Breast cancer (BC) adjuvant therapy after mastectomy in the setting of 1-3 positive lymph nodes has been controversial. This retrospective Translational Breast Cancer Research Consortium study evaluated molecular aberrations in primary cancers associated with locoregional recurrence (LRR) or distant metastasis (DM) compared to non-recurrent controls. We identified 115 HER2 negative, therapy naïve, T 1-3 and N 0-1 BC patients treated with mastectomy but no post-mastectomy radiotherapy. This included 32 LRR, 34 DM and 49 controls. RNAseq was performed on primary tumors in 110 patients; with no difference in RNA profiles between patients with LRR, DM or controls. DNA analysis on 57 primary tumors (17 LRR, 15 DM and 25 controls) identified significantly more NF1 mutations and mitogen activated protein kinase (MAPK) pathway gene mutations in patients with LRR (24%, 47%) and DM (27%, 40%) compared to controls (0%, 0%; p<0.0001 and p=0.0070, respectively). Three patients had matched primary vs LRR samples, one patient had a gain of a NF1 mutation in the LRR. There was no significant difference between the groups for PTEN loss or cleaved caspase 3 expression. The mean percentage Ki 67 labeling index was higher in patients with LRR (29.2%) and DM (26%) versus controls (14%,p= 0.0045). In summary, mutations in the MAPK pathway, specifically NF1, were associated with both LRR and DM, suggesting that alterations in MAPK signaling are associated with a more aggressive tumor phenotype. Validation of these associations in tissues from randomized trials may support targeted therapy to reduce breast cancer recurrence.
2018-09-14 | GSE119937 | GEO
Project description: Not available
| S-EPMC6185974 | biostudies-literature
Project description:We aimed to validate an 18-gene classifier (GC) initially developed to predict local/regional recurrence (LRR) after mastectomy in estimating distant metastasis risk.
2017-08-11 | GSE102484 | GEO
Project description:Background: Liver transplantation (LT) for Hepatocellular carcinoma (HCC) can be offered to patients beyond Milan criteria. However, there are currently no molecular markers that can be used on HCC explant histology to predict recurrence, which arises in up to 20% of LT recipients. The goal of our study was to identify proteins on HCC explant predictive of recurrence post-transplant, thereby guiding surveillance strategies and identifying patients beyond Milan criteria who would fare well following LT. Methods: LT recipients who had been transplanted at the University Health Network for HCC beyond Milan criteria in the context of Hepatitis B cirrhosis were identified. Snap-frozen samples from the dominant tumors of recurrent (N=7) and non-recurrent (N=4) patients were analyzed using LC-MS/MS on a Q-Exactive Plus mass spectrometer to delineate a distinctive proteomic signature. These tumors were also profiled by a Human Gene 2.0 ST microarray platform to identify a transcriptomic signature predictive of recurrence and analyzed with R packages. STRING database was used to characterize the implicated pathways. Kaplan-Meier estimator was used to generate a combined proteomic/transcriptomic signature predictive of HCC recurrence in patients with HCC beyond Milan criteria at time of LT. Significantly predictive proteins were verified and internally validated by immunoblotting or immunohistochemistry. Results: A total of 79 proteins and 636 genes were significantly differentially expressed in recurrent HCC, compared to non-recurrent (p<0.05). Among these, LGALS3, LGALS3BP, HAL, THBS1, and BLMH, were significantly increased in recurrent HCC at the protein and gene expression level. In turn, ALDH1A1 protein and gene expression were significantly decreased in recurrent HCC. Univariate survival analysis depicted ALDH1A1 (HR=0.084, 95%CI 0.01-0.68, p=0.02), LGALS3BP (HR=7.14, 95%CI 1.20-42.96, p=0.03), and LGALS3 (HR=2.89, 95%CI 1.01-8.3, p=0.049) as the key dysregulated proteins and genes in the patients with HCC recurrence versus those with non-recurrence by both proteomic and transcriptomic analysis. Decreased ALDH1A1 and significantly increased LGALS3 protein expression in recurrent HCC was verified by immunoblotting. Increased LGALS3BP protein expression in recurrent HCC was orthogonally verified and validated by immunohistochemistry in 30 independent HCC samples. Conclusion: Protein and gene expression of the cancer stem cell marker ALDH1A1 was protective against cancer recurrence in patients transplanted for HCC beyond Milan criteria. Conversely, increased expression of LGALS3 and LGALS3BP on explant was significantly predictive of post-transplant recurrence. These findings were internally validated, suggesting potential utility in identifying patients with HCC beyond Milan who would clearly benefit from transplant with limited recurrence risk and guiding post-transplant surveillance.
2022-02-22 | PXD022881 | Pride
Project description:Liver transplantation (LT) is an optimal treatment for a selected group of hepatocellular carcinoma (HCC) patients. However, about 10%-25% of LT cases develop post-transplant HCC recurrence, which drastically reduces the long-term survival of HCC patients. This study gives an analysis of the recurrent HCC after LT and the corresponding primary tumor. Results provide insight into the molecular mechanisms underlying post-LT HCC recurrence.
2021-08-27 | GSE102759 | GEO
Project description:Purpose: Investigate the molecular determinants of retinal regeneration in adult vertebrates by analyzing the gene expression profiles of control and post-lesion retina of adult zebrafish, a system that regenerates following injury. Methods: Gene expression profiles of zebrafish retina and brain were determined with DNA microarray, RT-PCR, and real-time quantitative PCR analyses. Damaged retinas and their corresponding controls were analyzed 2-5 days post-lesion (acute injury condition) or 14 d post-lesion (cell regeneration condition). Results: Expected similarities and differences in the gene expression profile of zebrafish retina and brain were observed, confirming the applicability of the gene expression techniques. Mechanical lesion of retina triggered significant, time-dependent changes in retinal gene expression. The induced transcriptional changes were consistent with cellular phenomena known to occur, in a time-dependent manner, subsequent to retinal lesion, including cell cycle progression, axonal regeneration, and regenerative cytogenesis. Conclusions: The results indicate that retinal regeneration in adult zebrafish involves a complex set of induced, targeted changes in gene transcription, and suggest that these molecular changes underlie the ability of the adult vertebrate retina to regenerate. Keywords: time course; injury response; cellular correlation Control brain and retina (unlesioned); Control and lesioned retina (matched animals, at least n = 8 for each condition).
2005-09-16 | E-GEOD-3303 | biostudies-arrayexpress
Project description:The derivation of molecular signatures indicative of disease status and predictive of subsequent behavior could facilitate the optimal choice of treatment for prostate cancer patients. In this study, we conducted a computational analysis of gene expression profile data obtained from 79 cases, 39 of which were classified as having disease recurrence, to investigate whether advanced computational algorithms can derive more accurate prognostic signatures for prostate cancer. At the 90% sensitivity level, a newly derived prognostic genetic signature achieved 85% specificity. This is the first reported genetic signature to outperform a clinically used postoperative nomogram. Furthermore, a hybrid prognostic signature derived by combination of the nomogram and gene expression data significantly outperformed both genetic and clinical signatures, and achieved a specificity of 95%. Our study demonstrates the feasibility of utilizing gene expression information for highly accurate prostate cancer prognosis beyond the current clinical systems, and shows that more advanced computational modeling of tissue-derived microarray data is warranted before clinical application of molecular signatures is considered. mRNA profiling was performed using 79 cases of prostate cancer of known disease recurrence status
2010-11-05 | E-GEOD-25136 | biostudies-arrayexpress
Project description:Comprehensive molecular characterization of liver cancer and inheritance of the phenotypic traits during tumor recurrence [methylation - recurrence]
| PRJNA449765 | ENA