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PROVIDER: PRJNA96407 | ENA |
REPOSITORIES: ENA
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Project description:BACKGROUND; Cisplatin-containing chemotherapy is the standard of care for patients with locally advanced and metastatic transitional cell carcinoma of the urothelium. The response rate is around 50% and tumor derived molecular prognostic markers are needed for estimation of response and survival. METHODS; Affymetrix GeneChip expression profiling was carried out using tumor material from 30 patients. A set of genes having an expression with high correlation to survival time after chemotherapy was identified. Two of these genes were selected for validation by immunohistochemistry (IHC) in tumor tissue from 149 cisplatin treated patients having complete follow-up data. RESULTS; Fifty-five differentially expressed genes correlated significantly to survival time. Two of these (Emmprin and Survivin) were validated using IHC, and multivariate analysis (n=145) identified Emmprin expression (hazard ratio 2.38; p<0.0001) and Survivin expression (hazard ratio 2.34; p<0.0001) as independent prognostic markers for poor outcome, together with the presence of visceral metastases (hazard ratio 2.72; p<0.0001). In the good prognosis group of patients without visceral metastases, both markers showed significant discriminating power as supplemental risk factors (p<0.0001). Within this group of patients, the subgroups of patients with no positive, one positive or two positive IHC stainings (Emmprin and Survivin) had estimated 5-year survival rates (+- SE) of 35.6+-?%, 6.3+-?%, and 0+?%, respectively. Response to chemotherapy could also be predicted with an OddsRatio of 4.60 (2.13-9.93) and 2.59 (1.25-5.38) for Emmprin and Survivin respectively. CONCLUSION; Emmprin and Survivin proteins were identified as strong independent prognostic predictors for response and survival after cisplatin-containing chemotherapy in patients with bladder cancer. Experiment Overall Design: Tumors from 30 patients with advanced bladder cancer used in the study. A SAM analysis was used for identifying genes co-varying with treatment response.
2008-06-13 | E-GEOD-5287 | biostudies-arrayexpress
Project description:Colorectal cancer (CRC) is the third most common lethal malignancy in Korea and worldwide. Rectal cancer patients occupy about 30% of CRC patients, and the majority of rectal cancer patients had locally advanced disease at diagnosis. The standard treatment of locally advanced rectal cancer (LARC) is neoadjuvant radiation therapy with concurrent chemotherapy (CCRT) followed by total mesorectal excision (TME). This multidisciplinary team approach improved local tumor control and overall survival of rectal cancer patients. High throughput proteomic analysis and machine learning algorithm identify DUOX2 (dual oxidase 2) as a novel biomarker for prediction of non-complete response after concurrent chemoradiation therapy for rectal cancer.High throughput proteomic analysis and machine learning algorithm identify DUOX2 (dual oxidase 2) as a novel biomarker for prediction of non-complete response after concurrent chemoradiation therapy for rectal cancer.
2023-03-11 | PXD023302 | Pride
Project description:For patients with muscle-invasive bladder cancer, there are no biomarkers in clinical use that can identify patients that are sensitive or resistant to neoadjuvant chemotherapy. This study investigates how molecular subtypes impact pathological response and survival in 149 patients receiving preoperative cis-platin based chemotherapy by tumor classification using transcriptomic profiling and a 13-marker immunostaining panel. Furthermore, we explored to what extent gene expression signatures can predict chemotherapy response beyond molecular subtypes. We observed improved pathological response rates and survival outcomes for patients presenting with genomically unstable (GU) and urothelial-like (Uro) subtypes compared to the basal-squamous (BASQ) subtype following neoadjuvant chemotherapy and radical cystectomy. Also, SPP1, coding for osteopontin, displayed a clear subtype-dependent effect on chemotherapy response, confirmed at the protein level. Based on our findings, we hypothesize that urothelial cancer of the luminal-like GU- and Uro-subtypes are more responsive to cisplatin-based chemotherapy which may influence patient selection pending further research.
2021-11-19 | GSE169455 | GEO
Project description:Prediction of progression-free survival in patients with advanced-stage serous ovarian cancer
| PRJNA118945 | ENA
Project description:MicroRNA signature predict chemotherapy response in patients with advanced colorectal cancer
| PRJNA210969 | ENA
Project description:The advent of neoadjuvant chemotherapy (NAC) prior to surgery and immune checkpoint therapy (ICT) have revolutionized bladder cancer management1-7. However, stratification of patients that would benefit most from these modalities remains a major clinical challenge. Here, we combine single nuclei RNA sequencing with spatial transcriptomics and single cell resolution spatial proteomic analysis of human bladder cancer to identify a novel epithelial subpopulation with therapeutic response prediction ability. These cells were defined by expression of Cadherin 12 (CDH12, N-Cadherin 2), catenins and other epithelial markers. CDH12-enriched tumors define patients with poor outcome following surgery with or without NAC. In contrast, CDH12-enriched tumors had a superior response to ICT. In all settings, patient stratification by tumor CDH12 enrichment offered better prediction of outcome than currently established bladder cancer subtypes. Molecularly, the CDH12 population resembles an undifferentiated state with inherent chemoresistance mediated through ALDH1A1 expression and fibroblast activation potential. Furthermore, CDH12-enriched cells express PD-L1 and PD-L2 and co-localize with exhausted T-cells, possibly mediated through CD49a (ITGA1), providing one explanation for ICT efficacy in these tumors. Altogether, this study describes a new cancer cell population with an intriguing diametric response to the major therapeutic modalities in bladder cancer. Importantly, it also provides a compelling rationale for the design of novel biomarker guided therapeutic clinical trials.
2021-06-04 | GSE171351 | GEO
Project description:The advent of neoadjuvant chemotherapy (NAC) prior to surgery and immune checkpoint therapy (ICT) have revolutionized bladder cancer management1-7. However, stratification of patients that would benefit most from these modalities remains a major clinical challenge. Here, we combine single nuclei RNA sequencing with spatial transcriptomics and single cell resolution spatial proteomic analysis of human bladder cancer to identify a novel epithelial subpopulation with therapeutic response prediction ability. These cells were defined by expression of Cadherin 12 (CDH12, N-Cadherin 2), catenins and other epithelial markers. CDH12-enriched tumors define patients with poor outcome following surgery with or without NAC. In contrast, CDH12-enriched tumors had a superior response to ICT. In all settings, patient stratification by tumor CDH12 enrichment offered better prediction of outcome than currently established bladder cancer subtypes. Molecularly, the CDH12 population resembles an undifferentiated state with inherent chemoresistance mediated through ALDH1A1 expression and fibroblast activation potential. Furthermore, CDH12-enriched cells express PD-L1 and PD-L2 and co-localize with exhausted T-cells, possibly mediated through CD49a (ITGA1), providing one explanation for ICT efficacy in these tumors. Altogether, this study describes a new cancer cell population with an intriguing diametric response to the major therapeutic modalities in bladder cancer. Importantly, it also provides a compelling rationale for the design of novel biomarker guided therapeutic clinical trials.
2021-06-04 | GSE169379 | GEO
Project description:To measure global gene expression in primary advanced colorectal cancer patients who have undergone fluorouracil, leucovorin and oxaliplatin (FOLFOX4) chemotherapy and screen valuable biomarkers to predict the effects of chemotherapy Samples from primary advanced colorectal cancer patients were collected. The effects of chemotherapy were evaluated, and patients were divided into an experimental group and a control group. All patients underwent standard FOLFOX4 regimen chemotherapy in four cycles after signing the chemotherapy agreement; subsequently, they were evaluated in accordance with the Response Evaluation Criteria In Solid Tumors (RECIST).Each samplewas collected immediately following resection. Each sample was divided in half: one half was fixed in formalin and embedded in paraffin; the other half floated in ice-cold phosphate-buffered saline and was stored in liquid nitrogen until total RNA extraction. CEL files available for only 16/30 samples. Remaining CEL files have been lost.
2015-12-31 | E-GEOD-69657 | biostudies-arrayexpress
Project description:BACKGROUND Cisplatin-containing chemotherapy is the standard of care for patients with locally advanced and metastatic transitional cell carcinoma of the urothelium. The response rate is around 50% and tumor derived molecular prognostic markers are needed for estimation of response and survival. METHODS Affymetrix GeneChip expression profiling was carried out using tumor material from 30 patients. A set of genes having an expression with high correlation to survival time after chemotherapy was identified. Two of these genes were selected for validation by immunohistochemistry (IHC) in tumor tissue from 149 cisplatin treated patients having complete follow-up data. RESULTS Fifty-five differentially expressed genes correlated significantly to survival time. Two of these (Emmprin and Survivin) were validated using IHC, and multivariate analysis (n=145) identified Emmprin expression (hazard ratio 2.38; p<0.0001) and Survivin expression (hazard ratio 2.34; p<0.0001) as independent prognostic markers for poor outcome, together with the presence of visceral metastases (hazard ratio 2.72; p<0.0001). In the good prognosis group of patients without visceral metastases, both markers showed significant discriminating power as supplemental risk factors (p<0.0001). Within this group of patients, the subgroups of patients with no positive, one positive or two positive IHC stainings (Emmprin and Survivin) had estimated 5-year survival rates (+- SE) of 35.6+-?%, 6.3+-?%, and 0+?%, respectively. Response to chemotherapy could also be predicted with an OddsRatio of 4.60 (2.13-9.93) and 2.59 (1.25-5.38) for Emmprin and Survivin respectively. CONCLUSION Emmprin and Survivin proteins were identified as strong independent prognostic predictors for response and survival after cisplatin-containing chemotherapy in patients with bladder cancer. Keywords: Analysis of gene expression differences between responders and non-responders to chemotherapy
2007-08-01 | GSE5287 | GEO