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:Locally advanced rectal cancer (LARC) exhibits heterogeneous responses to neoadjuvant chemoradiotherapy (nCRT), patients resistant to nCRT failing to benefit from to nCRT. The aim of this pilot study is to identify proteins associated with LARC nCRT-resistance. This pilot study retrospectively enrolled 4 representative nCRT-resistant (stable disease/progressive disease) and 4 nCRT-sensitive (complete response/partial response) patients, of which a total of 15 formalin-fixed paraffin-embedded tumor tissues (before and after nCRT) were subjected to data-independent acquisition mass spectrometry for proteomic analysis. Spectronaut software was employed for protein identification and quantification. Principal component analysis (PCA) was used to visualize intergroup differences in detected proteins. Differently abundant proteins in resistant patients (fold change ≥ 1.2 or ≤ 0.83 compare to sensitive patients) were selected for analysis using hierarchical clustering, cluster of orthologous groups, subcellular location, gene ontology, and pathway enrichment assay. A total of 39052 peptides and 6006 proteins were identified. PCA showed PCA clear separation among four groups: pre-treatment sensitive (B_S), pre-treatment resistant (B_R), post-treatment sensitive (P_S), and post-treatment resistant (P_R). Intergroup comparisons revealed before nCRT, 133 proteins were upregulated in the resistant group compared to the sensitive group, mainly localized in cytoplasm (33.08%), secreted (24.81%), and nucleus (24.06%), with functions enriched in cell junctions and metabolic related pathways. Post nCRT, 290 proteins were upregulated in the resistant group compared to the sensitive group, mainly localized in the nucleus (36.55%) and cytoplasm (23.10%), with functions enriched in replication, transcription, translation, and metabolic pathways. This study characterized DAP signatures of LARC with nCRT resistance, specific DAPs in resistant tumor provide references for mechanistic studies on treatment resistance, could be potential biomarker for response and therapeutic targets after further validation in larger cohorts.
| PXD069647 |
Project description:To characterize potential biomarkers and underlying mechanisms that prompt pathological complete response (pCR) rate of neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) patients.LARC patients from two hospitals were enrolled with pre-nCRT biopsy tissues examined by pressure cycling technology (PCT) combined with data-independent acquisition (DIA) mass spectrometry. Tumor regression grade (TRG) evaluation was performed with the surgical tissues after nCRT to estimate the efficacy of nCRT. Proteins up regulated in pCR patients were highlighted and immune infiltration analysis was carried out. The candidate biomarker FOSL2 (FOS Like 2, AP-1 Transcription Factor Subunit), was selected and verified its role in vitro and vivo. We then performed gene expression profiling analysis using data obtained from RNA-seq of 2 different cells with or without chemoradiotherapy.
2025-09-09 | GSE213009 | GEO
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:ObjectiveThis 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.BackgroundnCRT followed by total mesorectal excision (TME) is a standard treatment strategy for patients with LARC. Predicting the PCR to nCRT of LARC remine difficulty.Methods842 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.ResultsThe 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).ConclusionsThe 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: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
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: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