Unknown,Transcriptomics,Genomics,Proteomics

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Promoter methylation data from genomic DNA in patient with rectal cancer

ABSTRACT: The identification of surrogate methylation markers that can predict responses to preoperative chemoradiotherapy (CRT) in rectal cancer patients. Genome-wide association studies in clinical populations are theoretically capable of identifying markers that are capable of tumor regression after CRT. We used InfiniumM-BM-. Methylation Assay to detail methylation status of patientM-bM-^@M-^Ys group showing differential responsiveness to preoperative CRT and profiled SNP biomarkers. The chemoradiosensitivity of tumor tissue from the initial cohort of 45 patients was assessed using clinical responses of tumor regression grade (TRG). TRG was clinically categorized as complete response (CR) as TRG 1, dominant response (ER or finally as DR) as TRG 1 and 2, and efficient response (RYN or finally as ER) as TRG 1, 2, and 3 (TRG grade from Mandard et al, 1994). Examination of genome-wide DNA methylation in 45 colon cancer tissues. We separated patients into TRG1,2,3,4 and 5 group after chemoradiotherapy(CRT). As proposed by Mandard et al. TRG 1, complete tumor response; TRG2, residual cancer cells scattered through fibrosis; TRG 3, an increased number of residual cancer cells, with predominant fibrosis; TRG 4, residual cancer outgrowing fibrosis; and TRG 5, no regressive changes within the tumor: Responders (TRG 1 and 2) and nonresponders (TRG 3?5). Mandard et al. Cancer 1994 Group 1 and Group 2 in ER, CR and RYN was divided by TRG classification. CR: group 1 - TRG 2,3,4 and 5; group 2 - TRG 1 ER: group 1 - TRG 3,4,5; group 2 - TRG 1 and 2 RYN: group 1 - TRG 4 and 5; group 2 - TRG 1,2 and 3

ORGANISM(S): Homo sapiens

SUBMITTER: Jonglyul Park

PROVIDER: E-GEOD-39958 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Background: While much progress has been accomplished in the understanding of radiation-induced immune effects in tumors, little is known regarding the mechanisms involved at the tumor draining lymph node (TDLN) level following tumor irradiation. The objective of this retrospective study was to assess the immune and biological changes arising in TDLN upon concurrent chemoradiotherapy of primary non-small cell lung cancer (NSCLC) tumors. Methods: Patients with proved localized (cN0M0) NSCLC, treated by radical surgery plus lymph node dissection with (CRT+) or without (CRT-) neoadjuvant chemoradiotherapy, whereby radiotherapy was targeted on the primary tumor with no significant incidental irradiation of the TDLN station (stations XI or X), were identified. Bulk RNA-Seq of TDLNs was performed and data were analyzed based on differential gene expression (DEG) and gene sets enrichment. Results: Sixteen patients were included and 25 TDLNs were analyzed: 6 patients in the CRT+ group (12 samples) and 10 patients in the CRT- group (13 samples). Overall, 1001 genes were differentially expressed between the two groups (CRT+ and CRT-). Analysis with g-profiler revealed that gene sets associated with antitumor immune response, inflammatory response, hypoxia, angiogenesis, epithelial mesenchymal transition and extra-cellular matrix remodeling were enriched in the CRT+ group, whereas only gene sets associated with B cells and B-cell receptor signaling were enriched in the CRT- group. Unsupervised dimensionality reduction identified two clusters of TDLNs from CRT+ patients, of which one cluster (cluster 1) exhibited higher expression of pathways identified as enriched in the overall CRT+ group in comparison to the CRT- group. In CRT+ cluster 1, 3 out of 3 patients had pathological complete response (pCR) or major complete response (MPR) to neoadjuvant CRT, whereas only 1 out of 3 patients in the other CRT+ cluster (cluster 2) experienced MPR and none exhibited pCR. Finally, pathway comparison to published data from pre-metastatic TDLNs uncovered similarities with CRT+ cluster 1. Conclusion: Neoadjuvant concurrent chemoradiotherapy of the primary tumor in N0 NSCLC patients is associated with distinct microenvironment and immunological patterns in TDLNs as compared to TDLNs from patients with non-irradiated tumors. Our data are in line with studies showing superiority of lymph node sparing irradiation of the primary tumor in the induction of systemic antitumor immunity.

Project description:Using Human WG CodeLink microarrays, we established the expression profiling of 26 LARC without metastasis to gain insight into the molecular signatures associated with response to treatment after CRT. The study initially included a total of 35 consecutive patients with locally advanced rectal cancer (LARC) treated at Virgen de las Nieves Hospital from 2008 until 2010. Written informed consent was obtained from all the patients, and the study protocol was approved by the local Clinical Research (Ethics) Committee. They were distributed in two subgroups following a histological classification of response to treatment. Pretherapeutic staging was performed, including complete medical history and physical evaluation, digital rectal examination, endorectal ultrasound, rigid rectoscopy, colonoscopy, PET/TC and chest x-ray. Tumor samples were prospectively obtained during the rectoscopy. All patients subsequently received a total dose of 50.4Gy of radiatio (28 fractions of 1.8Gy) associated with capecitabine or capecitabine and oxaliplatine. Standardized surgery was performed, including total mesorectal excision, after an interval of 8 weeks after chemoradiotherapy. Tumor response was assessed in surgical specimen by semi-quantitative pathological examination (regression grade) including UICC stage. Histopathological tumor regression was graded based on the semiquantitative 5 point tumor regression grading (TRG) system: TRG1 or a TRG2 scores were considered Responders, whereas TRG3, TRG4, and TRG5 scores were classified as Non-Responders. In addition, the tumor regression or radiotherapy effects were assessed by positron emission tomography (18F-FDG PET). Tumor samples of LARC were collected from 35 patients. Nine patients were finally excluded due to the poor quality of the RNA or contradictory results of MandardM-BM-4s criteria and histopathological downstaging, resulting a total of 26 patients. Complete clinical data regarding, age, sex, stage of disease, response to therapy, and overall survival from 26 patients (10 responders and 16 non-responders) was provided in the sample characteristics field. CRT: Chemoradiation; Cap: Capecitabine; Capox: Capecitabine and Oxaliplatine; cTN: clinical stage; Surg: surgical technique; LAR: Low anterior resection; APR: Abdmino-perineal resection; HART: Hartmann, TRG: Tumor Regression Grade; Downst: Downstaging; Downs: downsizing, Resp: response, CPR: complete pathologic response

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Promoter methylation data from genomic DNA in patient with rectal cancer

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