DNA methylation-based classifier to predict pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal carcinomas.
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PROVIDER: PRJNA548688 | ENA |
REPOSITORIES: ENA
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Project description:Locally advanced rectal cancer (LARC) patients have been treated with a pre-operative multimodal regimen based on 5-fluorouracil and radiotherapy (nCRT) followed by surgery. Patients that achieve pathological complete response (pCR) present better overall survival and lower rates of recurrence. Substantial evidence indicate that these patients could be spared of surgery, while near 70% of cases present incomplete response (pIR), varying from partial response to stable-disease/progression. Markers capable of distinguishing pIR from pCR have the potential to address alternative treatment strategies. Herein, we evaluated the ability of predicting response to nCRT by DNA methylation analysis in pre-treatment biopsies of LARC.
2021-06-08 | GSE132668 | GEO
Project description:Most patients with locally advanced rectal cancer (LARC) present incomplete pathological response (pIR) to neoadjuvant chemoradiotherapy (nCRT). Despite the efforts to predict treatment response using tumor-molecular features, as differentially expressed genes, no molecule has proved to be a strong biomarker. The tumor secretome analysis is a promising strategy for biomarkers identification, which can be assessed using transcriptomic data. Here, we performed transcriptomic-based secretome analysis to select potentially secreted proteins using an in silico approach. The tumor expression profile of 28 LARC biopsies carefully selected and collected before nCRT was compared with normal rectal tissues (NT). The expression profile showed no significant differences between cases with complete (pCR) and incomplete response to nCRT. Genes with increased expression (pCR = 106 and pIR = 357) were used for secretome analysis based on public databases (Vesiclepedia, Human Cancer Secretome Database and Plasma and Proteome Database). Seventeen potentially secreted candidates (pCR=1, pIR=13 and 3 in both groups) were further investigated in two independent datasets (TCGA and GSE68204) confirming their over-expression in LARC. The potential secreted biomarkers were also confirmed as associated with the nCRT response (GSE68204). These putative proteins are candidates to be assessed in liquid biopsies aiming a personalized treatment in LARC patients.
2019-07-01 | GSE123390 | GEO
Project description:Locally advanced rectal cancer transcriptomic-based secretome analysis according to neoadjuvant chemoradiotherapy response
| PRJNA510936 | ENA
Project description:Objective This study aimed to develop an artificial intelligence model for predicting the pathological complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT) of locally advanced rectal cancer (LARC) using digital pathological images. Background nCRT followed by total mesorectal excision (TME) is a standard treatment strategy for patients with LARC. Predicting the PCR to nCRT of LARC remine difficulty. Methods 842 LARC patients treated with standard nCRT from three medical centers were retrospectively recruited and subgrouped into the training, testing and external validation sets. Treatment response was classified as pCR and non-pCR based on the pathological diagnosis after surgery as the ground truth. The hematoxylin & eosin (H&E)-stained biopsy slides were manually annotated and used to develop a deep pathological complete response (DeepPCR) prediction model by deep learning. Results The proposed DeepPCR model achieved an AUC-ROC of 0.710 (95% CI: 0.595, 0.808) in the testing cohort. Similarly, in the external validation cohort, the DeepPCR model achieved an AUC-ROC of 0.723 (95% CI: 0.591, 0.844). The sensitivity and specificity of the DeepPCR model were 72.6% and 46.9% in the testing set and 72.5% and 62.7% in the external validation cohort, respectively. Multivariate logistic regression analysis showed that the DeepPCR model was an independent predictive factor of nCRT (P=0.008 and P=0.004 for the testing set and external validation set, respectively). Conclusions The DeepPCR model showed high accuracy in predicting pCR and served as an independent predictive factor for pCR. The model can be used to assist in clinical treatment decision making before surgery.
| S-EPMC9214314 | biostudies-literature
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:BackgroundPatients with locally advanced rectal cancer (LARC) have an improved prognosis if achieved a pathological complete response (pCR) on account of neoadjuvant chemoradiation therapy (nCRT). However, the proportion of patients achieving pCR is only 8-24%. The purpose of this study was to explore whether the addition of consolidation chemotherapy to nCRT could improve pCR rate in patients with LARC.Materials and methodsThe subjects were 144 individuals with clinical stage II (T3-4, N0) or III (any T, N1-2) LARC who had received neoadjuvant CRT followed by total mesorectal excision (TME). Eighty-three patients in the consolidation chemotherapy group received two cycles XELOX between CRT and TME, while 61 patients in the standard treatment group without consolidation chemotherapy. The pCR (ypT0N0), tumor downstaging (ypT0-2N0) after TME and adverse events (AEs) during and post treatment were compared between the treatment groups using multivariable logistic regression analysis. To adjust the unbalanced variables for the primary endpoint, logistic regression analysis and stratified analysis were performed.ResultsThe consolidation chemotherapy group improved pCR rate (19.3% vs 4.9%, p = 0.01) and tumor downstaging rate (45.8% vs 24.6%, p = 0.009) compared to the standard treatment group. After adjustment for clinical tumor stage, clinical nodal stage and time interval to surgery, patients with consolidation chemotherapy were more likely to reach pCR (adjusted odds ratio 4.91, 95% CI [1.01-23.79], p = 0.048). AEs during and post treatment in the two groups were 54.1% vs 49.3% (p = 0.57), respectively. In addition, the incidence of any grade 1-2 AEs in the two groups was 93.4% vs 95.1% (p = 0.93), while the incidence of grade 3 AEs was 1.6% versus 2.4% (p = 0.74), respectively. No grade 4 AEs occurred in two groups.ConclusionsThe addition of neoadjuvant consolidation chemotherapy after CRT significantly increased the pCR rate and did not increase the AEs during and post treatment and in patients with LARC.
| S-EPMC7350921 | biostudies-literature
Project description:Recently, several circulating miRNAs have been reported as promising, minimally invasive biomarkers for the diagnosis or prediction of the prognosis in various types of cancer. However, the utility of circulating miRNAs as predictive markers of the cancer response to neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer is still unclear. To identify circulating serum miRNAs useful for predicting a pathological good response to nCRT, total 18 serum miRNAs of interest were analyzed by real-time polymerase chain reaction in 94 rectal cancer patients treated with nCRT and surgery. Pathological complete response (pCR; Dworak TRG4) and near-pCR (TRG3) were obtained in 12 (13%) and 9 (9%) patients respectively, and we regarded them as nCRT-responders. Of the 18 serum miRNAs, only the serum level of miR-143 was identified significantly associated with a pathological response to nCRT in 94 patients; the serum miR-143 level was significantly lower in nCRT-responders than in non-responders. A multivariate analysis incorporating other clinicopathological factors showed that only the serum miR-143 level was an independent predictor of a good pathological response. The circulating serum miR-143 level may be a novel, non-invasive predictive marker of a response to nCRT in locally advanced rectal cancer patients.
| S-EPMC5668032 | biostudies-literature
Project description:Background and purposeWith the advent of more intensive chemotherapy regimens, neoadjuvant chemoradiotherapy (NACRT) for patients with locally advanced rectal cancer (LARC) has always been questioned due to its inevitable radiation toxicity. Hence, we conducted a meta-analysis to compare the clinical efficacy of neoadjuvant chemotherapy (NAC) and NACRT.Materials and methodsEligible studies were searched using PubMed, MEDLINE, Embase, the Cochrane Library, and Web of Science up to 31 July 2020, comparing the clinical efficacy of NAC versus NACRT for LARC. Short- and long-term outcomes were determined using the odds ratio (OR) with 95% confidence interval (CI).ResultsSix studies with 12,812 patients were eligible for this meta-analysis, including 677 patients in the NAC group and 12,135 patients in the NACRT group. There were no significant differences between the two groups in terms of pathological complete response rate (OR=0.62, 95%CI=0.27~1.41), N down-staging rate (OR=1.20, 95%CI=0.25~5.79), R0 resection rate (OR=1.24, 95%CI=0.78~1.98), and local relapse rate (OR=1.12, 95%CI=0.58~2.14). The pooled OR for the total response rate and T down-staging were in favor of NACRT (OR=0.41, 95%CI=0.22~0.76 versus OR=0.67 95%CI=0.52~0.87). However, the pooled OR for the sphincter preservation rate favored NAC compared with NACRT (OR=1.87, 95%CI=1.24~2.81). Moreover, NAC was found to be superior to NACRT in terms of distant metastasis (14.3% vs. 20.4%), but the difference was not significant (OR=0.84, 95%CI=0.31~2.27).ConclusionWe concluded that NAC was superior to NACRT in terms of the sphincter preservation rate, and non-inferior to NACRT in terms of pCR, N down-staging, R0 resection, local relapse, and distant metastasis. However, the conclusion warrants further validation.
| S-EPMC8101236 | biostudies-literature
Project description:Background: MicroRNAs (miRNAs) are small, non-coding, RNA molecules which regulate numerous cellular processes. Specific miRNA may be abnormally down-regulated or up-regulated in colorectal cancer and have been found associated with prognosis or response to treatments. However, no study has ever addressed their predictive role in rectal cancer. Therefore, we used microarray technology and RT-PCR to profile miRNA expression patterns in patients (pts) with rectal cancer, with the aim to identify a specific M-bM-^@M-^\signatureM-bM-^@M-^] associated with pathological complete response after neoadjuvant chemo-radiotherapy. Methods: 38 pts with locally advanced rectal cancer (cT3-4/N+) were treated with capecitabine-oxaliplatin and pelvic conformal radiotherapy (45 cGy) followed by surgery (after 6-8 weeks). Pathologic response was scored according to the tumor regression grade (TRG) scale. MiRNA expression profile was analysed by microarray on fresh frozen biopsies obtained before treatment start and confirmed by RT-PCR. The correlation between miRNA expression profile and the TRG coded as TRG1 (pathologic Complete Response-pCR) versus TRG >1 (no pCR) was assessed by statistical analysis methods specifically designed for this study. Findings: 14 miRNAs were selected by arrays analysis as differentially expressed in TRG1 pts and 13 were confirmed by RT-PCR. In particular, 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909*, miR-630 and miR-765) were significantly up-regulated in TRG1 pts, while 2 miRNAs were under -expressed (miR-1274b and miR-720). miR-622 and miR-630 showed 100% sensitivity and specificity in selecting TRG1 cases and were significantly correlated with EGFR (M-OM-^G2=11M-bM-^@M-"793; p= 0M-bM-^@M-"001) and TS expression (M-OM-^G2=10M-bM-^@M-"589; p= 0M-bM-^@M-"001). Interpretation: A set of 13 miRNAs is strongly associated with pathologic complete response and may represent a specific marker of response to chemo-radiotherapy in locally advanced rectal cancer. Experiments were performed on purified RNA from preoperatory biopsies of 38 patients with histological diagnosis of rectal adenocarcinoma invading through the intestinal wall and/or with pelvic lymph node involvement as evaluated by endorectal ultrasonography (uT3-T4 and/or uN+). Patients were treated with neoadjuvant chemo-radiotherapy (capecitabine + oxaliplatin in combination with 45 Gy of pelvic conformal radiotherapy). Patients have been divided in the following two groups: group A those who had obtained a pathologic complete response M-bM-^@M-^S TRG 1, including the patient without detectable disease who refused surgery, group B any pathologic response other than complete.
2012-04-24 | E-GEOD-29298 | biostudies-arrayexpress
Project description:Preoperative chemoradiotherapy (CRT) followed by surgery has been proved to improve esophageal squamous cell carcinoma (ESCC) patients’ survival in comparison with surgery alone. However, the outcomes of CRT are heterogeneous, and no clinical or pathological method could predict CRT response. We aim to identify miRNA markers for ESCC CRT-response prediction through miRNA expression analyses.
2015-07-27 | GSE59974 | GEO