Project description:gene expression profiling of locally invasive breast carcinomas treated with preoperative radiotherapy the purose of this study was to establish molecular signature associated with response to radiotherapy using radiotherapy-naïve biopsies of locally advanced breast cancer
Project description:Cancer-associated fibroblasts (CAFs) are an important component of the desmoplastic stroma in rectal cancer. Preoperative chemoradiotherapy plays a pivotal role in the management of locally advanced rectal cancer. Patient-derived CAFs were used to evaluate the response to radiotherapy and its consequent impact on colorectal cancer cells (COLO320DM). COLO320DM cells were seeded and 24 hours later 1.8Gy irradiated. Subsequently, 24h later COLO320DM cells were treated with the secretome of 10x 1.8Gy irradiated CAFs or sham treated CAFs in 0.5% of serum. RNA was isolated 6 hours or 48 hours later.
Project description:A specific miRNA signature correlates with complete pathological response to neoadjuvant chemo-radiotherapy in locally advanced rectal cancer
Project description:This is Phase II Trial of 4courses of 5-fluorouracil, doxorubicin and cyclophosphamide follwed by 4 additional courses of weekly docetaxel and capecitabine administered as Preoperative Therapy for Patients with Locally Advanced Breast Cancer, Stages II and III by US oncology (PROTOCOL 02-103) We performed gene set analysis (GSA) using functionally annotated gene sets corresponding to almost all known biological processes in ER-positive/HER2negative and ER-negative/HER2-negative breast cancer, respectively. Pre-treatment FNA from primary tumors were obtained and RNA extracted and hybridized to afymetrix microarrays according to manufacturer protocol.
Project description:This is Phase II Trial of 4courses of 5-fluorouracil, doxorubicin and cyclophosphamide follwed by 4 additional courses of weekly docetaxel and capecitabine administered as Preoperative Therapy for Patients with Locally Advanced Breast Cancer, Stages II and III by US oncology (PROTOCOL 02-103) We performed gene set analysis (GSA) using functionally annotated gene sets corresponding to almost all known biological processes in ER-positive/HER2negative and ER-negative/HER2-negative breast cancer, respectively.
Project description:Background: Neoadjuvant radiotherapy (neo-RT) is widely used in locally advanced rectal cancer (LARC) as a component of radical treatment. Despite the advantages of neo-RT, which typically improves outcomes in LARC patients, the lack of reliable biomarkers that predict response and monitor the efficacy of therapy, can result in the application of unnecessary aggressive therapy affecting patients’ quality of life. Hence, the search for molecular biomarkers for assessing the radio responsiveness of this cancer represents a relevant issue. Methods: Here, we combined proteomic and metabolomic approaches to identify molecular signatures, which could discriminate LARC tumors with good and poor responses to neo-RT. Results: The integration of data on differentially accumulated proteins and metabolites made it possible to identify disrupted metabolic pathways and signaling processes connected with response to irradiation, including ketone bodies synthesis and degradation, purine metabolism, energy metabolism, degradation of fatty acid, amino acid metabolism, and focal adhesion. Moreover, we proposed multi-component panels of proteins and metabolites which could serve as a solid base to develop biomarkers for monitoring and predicting the efficacy of preoperative RT in rectal cancer patients. Conclusions: We proved that an integrated multi-omic approach presents a valid look at the analysis of the global response to cancer treatment from the perspective of metabolomic reprogramming.
Project description:A Nine-gene Signature for Predicting the Response to Preoperative Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer
Project description:Neoadjuvant chemoradiation therapy (CRT) is a widely used preoperative treatment strategy for locally advanced rectal cancer (LARC). However, a few studies have evaluated the molecular changes caused by neoadjuvant CRT in these cancer tissues. Here, we aimed to investigate changes in immunotherapy-related immunogenic effects in response to preoperative CRT in LARC. We analyzed 60 pairs of human LARC tissues before and after irradiation from three independent LARC cohorts, including a LARC patient RNA sequencing (RNA-seq) dataset from our cohort and GSE15781 and GSE94104 datasets. Gene ontology analysis showed that preoperative CRT significantly enriched the immune response in LARC tissues. Moreover, gene set enrichment analysis revealed six significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways associated with downregulated genes, including mismatch repair (MMR) genes, in LARC tissues after CRT in all three cohorts. Radiation also induced apoptosis and downregulated various MMR system-related genes in three colorectal cancer cells. One patient with LARC showed a change in microsatellite instability (MSI) status after CRT, as demonstrated by the loss of MMR protein and PCR for MSI. Moreover, CRT significantly increased tumor mutational burden in LARC tissues. CIBERSORT analysis revealed that the proportions of M2 macrophages and CD8 T cells were significantly increased after CRT in both the RNA-seq dataset and GSE94104. Notably, preoperative CRT increased various immune biomarker scores, such as the interferon-γ signature, the cytolytic activity and the immune signature. Taken together, our findings demonstrated that neoadjuvant CRT modulated the immune-related characteristics of LARC, suggesting that neoadjuvant CRT may enhance the responsiveness of LARC to immunotherapy.
