Type I IFN Signaling Drives Responsiveness to Short Course Radiotherapy in a Murine Model of Rectal Cancer
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ABSTRACT:
PROVIDER: PRJNA946734 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23920300.fastq.gz | Fastqsanger.gz | |||
| SRR23920301.fastq.gz | Fastqsanger.gz | |||
| SRR23920302.fastq.gz | Fastqsanger.gz | |||
| SRR23920303.fastq.gz | Fastqsanger.gz | |||
| SRR23920304.fastq.gz | Fastqsanger.gz |
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Project description:Specific cell types from orthotopic murine rectal tumors were sequenced to explore the effect that short course radiotherapy has on the immune response.
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2009-11-10 | E-MEXP-1901 | biostudies-arrayexpress
Project description:Background: Neoadjuvant radiotherapy (neo-RT) is widely used in locally advanced rectal cancer (LARC) as a component of radical treatment. Despite the advantages of neo-RT, which typically improves outcomes in LARC patients, the lack of reliable biomarkers that predict response and monitor the efficacy of therapy, can result in the application of unnecessary aggressive therapy affecting patients’ quality of life. Hence, the search for molecular biomarkers for assessing the radio responsiveness of this cancer represents a relevant issue. Methods: Here, we combined proteomic and metabolomic approaches to identify molecular signatures, which could discriminate LARC tumors with good and poor responses to neo-RT. Results: The integration of data on differentially accumulated proteins and metabolites made it possible to identify disrupted metabolic pathways and signaling processes connected with response to irradiation, including ketone bodies synthesis and degradation, purine metabolism, energy metabolism, degradation of fatty acid, amino acid metabolism, and focal adhesion. Moreover, we proposed multi-component panels of proteins and metabolites which could serve as a solid base to develop biomarkers for monitoring and predicting the efficacy of preoperative RT in rectal cancer patients. Conclusions: We proved that an integrated multi-omic approach presents a valid look at the analysis of the global response to cancer treatment from the perspective of metabolomic reprogramming.
2024-05-22 | PXD048647 | Pride
Project description:With a view to developing novel biomarkers of the efficacy of radiotherapy in patients with rectal cancer, we measured gene expression profiles on biopsies taken before and during preoperative radiotherapy. Repeat biopsy did not increase toxicity. Radiotherapy induced the expression of genes involved in oxidative stress, signal transduction, apoptosis and immune response.
2011-12-12 | GSE26027 | GEO
Project description:With a view to developing novel biomarkers of the efficacy of radiotherapy in patients with rectal cancer, we measured gene expression profiles on biopsies taken before and during preoperative radiotherapy. Repeat biopsy did not increase toxicity. Radiotherapy induced the expression of genes involved in oxidative stress, signal transduction, apoptosis and immune response. Two rectum tumor biospsies for each patient (6 cases) : before RT and one hour after a dose of 7.2 Gy (4th fraction) during RT.
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Project description:Radiotherapy constitutes a pivotal approach in the management of pelvic malignant tumors. Despite notable strides in radiation technology, the incidence of collateral damage to neighboring normal tissues remains a prominent concern. Radiation-induced rectal injury (RRI) significantly impacts the postoperative quality of life of patients undergoing pelvic radiotherapy. We gathered RRI tissues alongside non-irradiated rectal tissues for a quantitative proteomic examination employing data-independent acquisition proteomics. Our analysis unveiled differentially expressed proteins (DEPs). Gene Ontology and Kyoto Encyclopedia of Genes and Genome enrichment analyses of DEPs uncovered conventional pathway modifications such as cytokine activation and extracellular matrix alterations, alongside emerging potential biological mechanisms implicated in RRI, including neutrophil extracellular traps, macrophage-to-myofibroblast transition, and metabolic reprogramming.
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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.
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Project description:Exosomes may be used as biomarkers for the prediction and monitoring of response to anti-cancer treatment, yet relevant knowledge is very limited in the case of rectal cancer. Here we applied a combined proteomic and metabolomic approach to reveal exosome components connected with different responses to neoadjuvant radiotherapy in this group of patients and processes associated with identified discriminatory molecules. Moreover, the composition of serum-derived exosomes and a whole plasma was analyzed in parallel to compare the biomarker potential of both specimens, which revealed the highest capacity of exosome proteome to discriminate samples of patients with different responses to radiotherapy.
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Project description:Non-operative management of rectal cancer is increasingly being used in selected patients. Most reports include patients treated with chemoradiotherapy (CRT) before inclusion into a Watch & Wait (W&W) programme. The aim of this study was to report outcomes from a single-centre W&W programme involving a large cohort of patients. Patients treated with chemoradiotherapy (CRT) or short-course radiotherapy (SCRT) with or without chemotherapy, between 2008 and 2020, who showed signs of a clinical complete response (cCR) were reviewed. Patients were assessed using digital rectal examination, flexible endoscopy, carcinoembryonic antigen measurement, MRI, and CT imaging, discussed at the multidisciplinary tumour board meeting, and followed up in a dedicated W&W programme as from 2015. Outcomes including regrowth and 3-year survival (time to regrowth or death) were prospectively evaluated. Of 142 patients who were assessed, 88 fulfilled the criteria for cCR. Treatment before cCR included CRT, SCRT with chemotherapy, and SCRT alone in 16 (18 per cent), 28 (32 per cent), and 44 (50 per cent) patients, respectively. Patients treated with CRT and SCRT with chemotherapy had more advanced clinical T- and N-stage, compared with patients treated with SCRT alone (clinical T-stage > 2: 81 per cent and 89 per cent versus 47 per cent, respectively; clinical N-stage > 0: 75 per cent and 93 per cent versus 68 per cent, respectively). Overall rate of regrowth was 19 per cent, with 31 per cent, 21 per cent, and 14 per cent following CRT, SCRT with chemotherapy, and SCRT alone, respectively. Uni- and multivariable analyses evaluating the clinical parameters revealed no statistically significant associations with risk of local regrowth. All but one patient with regrowth underwent salvage surgery. The 3-year survival rate (death with regrowth as competing risk) was 93 per cent, with no significant difference between treatment groups. In this cohort of W&W patients, the vast majority received SCRT with or without chemotherapy and results consistent with previous W&W reports were obtained. No statistically significant differences in terms of regrowth rate were obtained when comparing CRT, SCRT with chemotherapy, and SCRT alone. SCRT can induce sustained cCR and may precede a W&W strategy.
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