Project description:To elucidate candidate genes and pathways associated with poor response, we retrospectively analyzed gene expression profiles in serial biopsies from women with locally advanced breast cancer who failed to respond to anthracycline-based chemo followed by taxane in the I-SPY Of the 221 patients who completed neoadjuvant chemotherapy, 215 patients had surgery with 73% not achieving a pathologic complete response (pathCR). In these patients, cDNA microarray expression profiles from pretreatment biopsy (T1) were compared to those biopsy specimens obtained 24-72 hours after initiation of treatment (T2) or in tumors surgically removed after chemotherapy (TS). Paired expression data for T1vsT2 and T1vsTS were available for 29 and 39 patients with no pathCR, respectively. Paired differential expression analyses were performed via Significance Analysis of Microarrays (SAM) and differentially expressed genes were subjected to Ingenuity Pathway Analysis
Project description:Purpose: Identified the expression profile of lncRNAs associated to neoadjuvant chemotherapy response in 47 luminal B tumors of locally advanced breast cancer patients Methods: We implemented the transcriptomic analysis from 47 luminal B breast cancer samples by paired-end RNA-Seq, as a case-control study (responders vs nonresponders group). Differential expression analysis for lncRNA and mRNA were made to identify lncRNA as predictive biomarkers. Results: We identified a signature of lncRNAs associated with nonresponders group. Additionally, we identified the pathways were differentially expressed lncRNA and mRNA are associated in neoadjuvant chemotherapy response. Additionally, we proposed the clinical application of lncRNA GATA3-AS1 as a predictive biomarker to neoadjuvant chemotherapy response in luminal B breast cancer patients detected by RNA-ISH. Conclusion: we propose the clinical utility of lncRNA GATA3-AS1 detected by RNA-ISH to identify luminal B breast cancer patients that will not respond to neoadjuvant chemotherapy.
Project description:Purpose: Identified the expression profile of lncRNA associated to neoadjuvant chemotherapy response in 11 tumor of locally advanced breast cancer patients Methods: We implemented the transcriptomic analysis from 11 breast cancer samples by paired-end RNA-Seq, as a case-control study (responders vs nonresponders group). Differential expression analysis for lncRNA and mRNA were made to identify lncRNA as predictive biomarkers. Results: We identified the over-expressed lncRNA GATA3-AS1 in nonresponders group. Additionally, we identified the pathways were differentially expressed lncRNA and mRNA are associated in neoadjuvant chemotherapy response. Conclusion: we propose lncRNA GATA3-AS1 as a potential predictive biomarker for patients with LABC luminal B-like subtype that will not respond to neoadjuvant chemotherapy
Project description:To elucidate candidate genes and pathways associated with poor response, we retrospectively analyzed gene expression profiles in serial biopsies from women with locally advanced breast cancer who failed to respond to anthracycline-based chemo followed by taxane in the I-SPY
Project description:Background. There is evidence that the stromal compartment may influence breast cancer responsiveness to chemotherapy. Our aim was to detect a stromal cell signature (using a direct approach of microdissected stromal cells) associated with response to neoadjuvant chemotherapy in locally advanced breast cancer, considering tumor down staging (to at least ypT1a/b,ypN0), as the best response. Patients and methods. Forty four patients diagnosed with locally advanced breast cancer (29 classified as estrogen receptor (ER) positive and 15, as ER negative) were included. Neoadjuvant chemotherapy consisted of doxorubicin/cyclophosphamide, followed by paclitaxel. Response was defined as downstaging to maximum ypT1a-b/ypN0. Stromal cells were microdissected from fresh frozen tumor samples and gene expression profile was determined using Agilent SurePrint G3 Human Gene Expression Microarrays. Expression levels were compared using MeV (MultiExperiment Viewer) software, applying SAM (Significance analysis of microarrays). Gene set enrichment analysis was used to identify gene sets correlated with the phenotype downstaging. Results: After chemotherapy, nine patients presented disease downstaging to maximum ypT1a-b/ypN0. Using SAM test (FDR 17), 11 sequences were differentially expressed, all of which (except for H2AFJ) more expressed in responsive tumors. Gene list enrichment analysis revealed three genes involved in abnormal cytotoxic T cell physiology: TOX, LY75 and SH2D1A. Gene sets correlated with tumor downstaging (FDR < 0.01), were mainly involved in immune response or lymphocyte activation, both in ER positive and ER negative samples. Conclusion: In locally advanced breast cancer, stromal cells may present specific features of immune response that may be associated with chemotherapy response.
Project description:MicroRNAs (miRNAs) have been recently detected in the circulation of cancer patients, where they are associated with clinical parameters. Discovery profiling of circulating small RNAs has not been previously reported in breast cancer (BC), and was carried out in this study to identify blood-based small RNA markers of BC clinical outcome. The pre-treatment sera of 42 stage II–III locally advanced and inflammatory BC patients who received neoadjuvant chemotherapy (NCT) followed by surgical tumor resection were analyzed for marker identification by deep sequencing all circulating small RNAs.
Project description:The patients with locally advanced squamous cervical cancer (SCC) were examined in this study. All patients received neoadjuvant chemotherapy followed by radical hysterectomy. Tumor response against NAC was determined based on RECIST criterior. Gene-expression profiles of SCC were determined using Human Genome GeneChip arrays U133.
Project description:Aggressive breast tumors are routinely treated with pre-operative chemotherapy. However, a subset of patients have recurrence despite adjuvant treatment. To identify metabolic processes involved in drug resistance, we took a mass spectrometry-based proteomic approach, and analyzed a breast cancer cohort of 113 samples comprising of breast tumors before and after chemotherapy, with matched tumor adjacent normal tissue from partial responders that underwent neoadjuvant treatment (NAT). Pattern analysis of 7180 proteins revealed more than 1000 proteins with significantly differential expression in primary tumor relative to the healthy tissue, which do not respond to treatment, in treatment resistant patients. Among those, we found significant upregulation of the proline biosynthesis pathway, primarily, PYCR1 that significantly correlated with lower recurrence free survival time in our cohort. Functional analysis showed that PYCR1 induced a pro-survival effect upon treatment with chemotherapy drugs thus emphasizing the potential role of PYCR1 in drug resistance in advanced breast cancer.
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.
Project description:The patients with locally advanced squamous cervical cancer (SCC) were examined in this study. All patients received neoadjuvant chemotherapy followed by radical hysterectomy. Tumor response against NAC was determined based on RECIST criterior. Gene-expression profiles of SCC were determined using Human Genome GeneChip arrays U133. SCC patients who had undergone radical hysterectomy after NAC were studied. To identify molecular signatures to predict response to NAC using Irinotecan/Nedaplatin, gene expression profiles were compared between NAC Reponder and Non-responder.