Gene expression profiling study by RNA-seq to identify gene signature resposed to chemo-radiotherapy in colorectal cancers.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE80606 | GEO | 2020/12/25
REPOSITORIES: GEO
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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.
2012-04-24 | E-GEOD-29298 | biostudies-arrayexpress
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.
2023-12-14 | GSE239514 | GEO
Project description:Radiotherapy and adjuvant cisplatin (DDP) chemotherapy are standard administrations applied in the treatment of NPC. However, molecular change and functions of DDP chemo-resistance in nasopharyngeal carcinoma are still poorly understood.
2019-08-01 | GSE135083 | GEO
Project description:Human colon cancer cells HT29, HCT116, LoVo robustly expressed PD-1. PD-1 signaling significantly decreased proliferation and promoted apoptosis in PD1+human colon cancer cells. The human anti-PD-1, Nivolumab (NIVO) ptomoted proliferation through pERK/pAKT signaling, reduced apoptosis and protected PD-1+ cells from Chemo/Radiotherapy (CRT). In vivo, NIVO promoted HT29 tumor growth reducing Oxaliplatin (OX) efficacy. As opposite to colon cancer cells, PD-1 signaling protects melanoma cells, thus NIVO treated human colon versus melanoma cancer cells, PES43 were evaluated for RNAseq. Among the commonly affected genes, opposite regulation was revealed between HT29 and HCT116 colon versus PES43 melanoma cells. BATF2, DRAM1, FXYD3, IFIT3, MT-TN, TNFRSF11A were upregulated in PES43 and downregulated in HT29 and HCT116 while CLK1, DCAF13, DNAJC2, MTHFD1L, PRPF3, PSMD7, SCFD1 were downregulated in PES43 and upregulated in HT29 and HCT116. DEGs were significantly enriched in the functional categories of the interferon pathway, innate immune, cytokine-mediated signaling pathway, neutrophil activation, immune effector process, granulocyte activation and cellular nitrogen compound metabolic process. Moreover, intrinsic PD-1 was expressed in 11/48 (22.9%) primary colorectal cancer and associated with tumor dimension (pT). Thus, PD-1 inhibition through NIVO protects human colon cancer cells and activate tumor survival pathways
2022-03-08 | GSE174252 | GEO
Project description:To investigate mRNA expression difference in cisplatin chemo-sensitivity in esophageal squamous carcinoma patients. We performed gene expression profiling analysis using data obtained from RNA-seq of 6 different patients.
2023-05-01 | GSE229974 | GEO
Project description:The recruitment of monocytes and their differentiation into immunosuppressive cells is associated with the negative outcome of non-conformal radiotherapy (RT). However, non-conformal RT is irrelevant in the clinic, and little is known about the role of monocytes following radiotherapy modes used in patients, such as conformal radiotherapy (CRT). Here, we investigated the acute immune infiltration post-CRT. Contrary to non-conformal RT approaches, we found that CRT induces a rapid and robust recruitment of monocytes to the tumor that minimally differentiate into tumor-associated macrophages (TAM) or dendritic cells (DC), but instead upregulate major histocompatibility complex II (MHCII) and costimulatory molecules. We establish that these large numbers of infiltrating monocytes are responsible for increasing type I interferon in the tumor microenvironment (TME), activation of CD8+ T cells and the reduction in tumor burden. Importantly, we demonstrate that rapid monocyte infiltration to the TME is hindered when RT inadvertently affects healthy tissues. Our results unravel a positive role of monocytes during clinically relevant modes of RT and demonstrate that limiting exposure of healthy tissues to radiation has a positive therapeutic effect on the overall immune response within the tumor.
2022-06-30 | MSV000089775 | MassIVE
Project description:We performed RNA sequencing on 10 bulk pre-chemo tumor samples collected from 5 patients with HGSOC.
2020-12-14 | GSE160085 | GEO
Project description:The clinical management of locally advanced oesophageal adenocarcinoma (OAC) commonly involves neoadjuvant chemoradiotherapy (CRT), but complete pathological response to CRT only occurs in 20-30% of patients, as radioresistance remains a major clinical challenge. In this study we used an established isogenic cell line model of radioresistant OAC to detect proteomic signatures of radioresistance in order to identify novel potential molecular and cellular targets of radioresistance in OAC. Intracellular proteins obtained from radiosensitive (OE33P) and radioresistant (OE33R) cells were subjected to LC-MS/MS analysis. We identified 5785 proteins of which 251 were significantly modulated in OE33R cells, when compared to OE33P. Gene ontology and pathway analysis of the significantly modulated proteins demonstrated altered metabolism in radioresistant cells accompanied by an inhibition of apoptosis in OE33R cells. In addition, radioresistant cells were predicted to have an activation of inflammatory and angiogenic pathways when compared to the radiosensitive cells. For the first time, we performed a comprehensive proteomic profiling of our established isogenic cell line model of radioresistant OAC, providing insights into the molecular and cellular pathways which regulates radioresistance in OAC, and we provided pathway specific signatures of radioresistance that will aid further studies on the development of targeted therapies and personalised approaches to radiotherapy, with the ultimate goal of improving response to radiotherapy in cancer patients.
2022-08-18 | PXD020303 | Pride
Project description:Emerging evidence suggests that an increased density of pre-treatment CD8+ tumor-infiltrating lymphocytes (TILs) is associated with good response to chemoradiotherapy (CRT) in patients with locally advanced rectal cancer. However, the significance of T-cell complexity in the clinical setting remains unknown. High-throughput T-cell receptor (TCR) β sequencing was applied to quantify the TCR repertoire of pre-treatment biopsies from 67 patients with advanced rectal cancer receiving preoperative CRT. Changes in TCR repertoire before and after CRT were also analysed in 23 patients.
2022-11-22 | GSE218181 | 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 “signature” 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 (χ2=11•793; p= 0•001) and TS expression (χ2=10•589; p= 0•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.
2012-04-25 | GSE29298 | GEO