Long Non-coding RNA expression predictive of tumour response in patients treated with preoperative chemoradiotherapy for LARC
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE145666 | GEO | 2020/02/22
REPOSITORIES: GEO
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Project description:The treatment strategy of rectal cancer has substantially changed in recent decades. Historically postoperative chemoradiotherapy (CRT) was considered to be the first-line therapy for stage II and III rectal cancers. However, the preoperative CRT is now considered to be the optimal therapy regimen for locally advanced rectal ancer due to its improved local control, reduced toxicity, and increased rate of sphincter preservation. Our study established a clinically practical multi-class prediction model by adopting a novel strategy that applies two separate prediction models (MI and TO predictor) sequentially to a patient to predict the response. For promising clinical practice, we validated our model in a published dataset, which is completely independent dataset from ours. This study suggests a clinically plausible prediction model that correctly infers the preoperative CRT response of patients with high accuracy based on 163 gene signatures we identified. Total RNAs were isolated from primary rectal tumor tissues of 69 patients who underwent chemoradiation therapy (CRT). These patients are classified into four different CRT responses: minimal response (MI), moderate response (MO), near total response (NT) and total response (TO). All the RNAs were subjected to microarray analysis using Affymetrix GenChip arrays.
2013-05-14 | E-GEOD-46862 | biostudies-arrayexpress
Project description:The treatment strategy of rectal cancer has substantially changed in recent decades. Historically postoperative chemoradiotherapy (CRT) was considered to be the first-line therapy for stage II and III rectal cancers. However, the preoperative CRT is now considered to be the optimal therapy regimen for locally advanced rectal ancer due to its improved local control, reduced toxicity, and increased rate of sphincter preservation. Our study established a clinically practical multi-class prediction model by adopting a novel strategy that applies two separate prediction models (MI and TO predictor) sequentially to a patient to predict the response. For promising clinical practice, we validated our model in a published dataset, which is completely independent dataset from ours. This study suggests a clinically plausible prediction model that correctly infers the preoperative CRT response of patients with high accuracy based on 163 gene signatures we identified.
2013-05-14 | GSE46862 | GEO
Project description:A total of 97 LARC patients treated at the Institute for Oncology and Radiology of Serbia in the period of 2018-2019 were included in the study. Patients were treated with long-course chemoradiotherapy (CRT): Radiotherapy (RT) was delivered with a total dose of 50.4 Gy in 28 fractions; concomitant chemotherapy (5-FU, 350 mg/m2 daily) and Leucovorin (25 mg/m2 daily) was administered during the first and the fifth week of RT. Patients were evaluated in week 6-8 after treatment completion with pelvic MRI scan and rigid proctoscopy. Pathohistological response after surgery was assessed according to tumor regression grading (TRG) categories by Mandard. Twenty biopsy samples taken at diagnosis were used for proteomic analysis, 9 responders (R, TRG 1-2), and 11 non-responders (NR, TRG 3-5), in order to achieve the maximum range of different molecular features potentially associated with response.
2023-11-21 | PXD040451 | Pride
Project description:Importance: Neoadjuvant chemoradiotherapy (CRT) is the standard of care for advanced rectal cancer. Yet, predicting response to CRT remains an unmet clinical challenge. Objective: To investigate the transcriptomic determinants to predict response to neoadjuvant CRT and survival in patients with advanced rectal cancer. Design: A single-center, retrospective, cohort study. Setting: A comprehensive cancer center. Participants: Pre-treatment biopsies from 298 patients with rectal cancer, who were later treated with neoadjuvant CRT between 2004 and 2020, were analyzed by RNA sequencing. Main measures and outcomes: Transcriptional subtyping was performed by consensus molecular subtype (CMS) classification. Immune cell infiltration was assessed using MCP-counter scores and single-sample gene set enrichment analysis (ssGSEA). Patients with surgical specimens of tumor regression grade (TRG) 3-4 or who were managed by the watch-and-wait approach for more than 3 years were defined as good responders. Results: Patients classified as CMS1 (6.4%) had a significantly higher rate of good responders; albeit survival was comparable among the four subtypes. Good responders exhibited an enrichment in various immune-related pathways (IFNg and a responses, allograft rejection, IL6 STAT3 signaling during acute phase response, and inflammation), as determined by ssGSEA. MCP-counter scores for cytotoxic lymphocytes were significantly higher for good responders than non-responders (p = 0.0003), and significantly higher for responders than non-responders in GSE109057 (p = 0.0137), GSE87211 (p = 0.0092), and GSE45404 (p = 0.0327) datasets. Cytotoxic lymphocyte MCP-counter score was thus considered an independent predictor of response to CRT, as determined in the multivariable Cox analysis (OR 3.810 [95% CI 1.820-7.970]; p = 0.0004). Multivariable Cox analysis, including post-operative pathological factors, revealed cytotoxic lymphocyte MCP-counter score to be independently associated with recurrence-free survival (HR 0.382 [95% CI 0.158-0.923]; p = 0.0325) and overall survival (HR 0.157 [95% CI 0.030-0.827]; p = 0.0290). ssGSEA showed significantly higher levels of four subpopulations of cytotoxic cells (effector memory CD8 T, natural killer T, natural killer, and activated CD8 T cells) among good responders than non-responders. Conclusions and Relevance: Cytotoxic lymphocyte score, as computed by RNA sequencing, could be a useful marker for predicting response to CRT and survival among patients with rectal cancer.
2023-01-25 | GSE216616 | GEO
Project description: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
2014-08-01 | E-GEOD-39958 | biostudies-arrayexpress
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
2014-01-03 | E-GEOD-53781 | biostudies-arrayexpress
Project description: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 Infinium® Methylation Assay to detail methylation status of patient’s 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).
2014-08-01 | GSE39958 | GEO
Project description:The identification of surrogate single nucleotide polymorphism (SNP) 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 Affymetrix’s SNP Array 6.0 to detail genetic polymorphism of patient’s group showing differential responsiveness to preoperative CRT and profiled SNP biomarkers. The chemoradiosensitivity of tumor tissue from the initial cohort of 43 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). Blood DNAs were prepared from each patients and hybridized to Affymetrix’s SNP Array 6.0. Genotypes were determined using the Affymetrix Genotyping Console software (version 2.1) based on the BRLMM-P algorithm. We used an ANOVA test to identify SNPs associated with quantitative TRG responses.
2012-12-31 | E-GEOD-35282 | biostudies-arrayexpress
Project description:To measure global gene expression in primary locally advanced rectal cancer patients who have undergone CRT and screen valuable biomarkers to predict the effects of CRT.Samples fromprimary locally advanced rectal cancer patients were collected. The effects of chemoradiotherapy were evaluated.
2021-06-04 | GSE145037 | GEO
Project description:The incorporation of chemoradiation prior to resection of the tumour has revolutionized the management of locally advanced rectal cancer. However, a large proportion of these patients are resistant to preoperative treatment schedule. We recently reported that c-Myc gene expression correlates negatively with this resistance in patients with rectal cancer. In this study, we carried out integrated analysis of miRNA and mRNA expression profiling in 45 pre-treatment rectal tumour. Further, expression of miRNAs and c-Myc, and their relationship with clinicopathological factors and patient survival was analysed. As a result, we found that 12 miRNAs were differentially expressed between responder and non-responder rectal cancer patients. Functional classification revealed an association between differentially expressed miRNAs and c-Myc. Subsequent quantitative real-time PCR results showed that both, miRNA-148 and miRNA-375 levels were significantly lower in responder compared to non-responder patients. Notably, the higher level of miRNA-375 was significantly negatively correlated with c-Myc. These results suggest that miRNA-375 and its targeted c-Myc play an important role as predictive biomarker of response to neoadjuvant treatment in patients with locally advanced rectal cancer, but still not suitable for prognosis. Pre-treatment biopsies of 22 patients with LARC were prospectively collected and freshly frozen according to an institutional board-approved protocol. Tumour response was assessed in surgical specimens by pathological examination based on the semi-quantitative tumour regression grading (TRG) system described by Mandard in 1994[36]: TRG1 and TRG2 scores were considered responders, whereas TRG3, TRG4, and TRG5 were classified as non-responders. The inclusion criteria were: histologically proven rectal tumour at a clinical stage UICC II-III (cT3-4/and or N positive), following endorectal ultrasound and/or MRI scan. Patients were excluded if they had the tumour located above 13 cm from the anal verge by rigid rectoscopy, synchronic colonic cancer assessed by colonoscopy, distant metastases by 18FDG PET-CT scan, and suspicion of hereditary colorectal cancer. All patients subsequently received a total dose of 50.4Gy of radiation (28 fractions of 1.8Gy) associated with capecitabine (oral form of 5-FU) with or without oxaliplatine, according to our Hospital Clinical Practice Guidelines. Standardized Surgery was performed, including total mesorectal excision, following an interval of 8-10 weeks after completion of CT/RT.
2017-05-17 | GSE98959 | GEO