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Predicting multi-class responses to preoperative chemoradiotherapy in rectal patients

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE46862 | GEO | 2013/05/14

SECONDARY ACCESSION(S): PRJNA202902

REPOSITORIES: GEO

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Predicting multi-class responses to preoperative chemoradiotherapy in rectal patients

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

Neoadjuvant chemoradiation alters biomarkers of anticancer immunotherapy responses in locally advanced rectal cancer

Project description:Neoadjuvant chemoradiation therapy (CRT) is a widely used preoperative treatment strategy for locally advanced rectal cancer (LARC). However, a few studies have evaluated the molecular changes caused by neoadjuvant CRT in these cancer tissues. Here, we aimed to investigate changes in immunotherapy-related immunogenic effects in response to preoperative CRT in LARC. We analyzed 60 pairs of human LARC tissues before and after irradiation from three independent LARC cohorts, including a LARC patient RNA sequencing (RNA-seq) dataset from our cohort and GSE15781 and GSE94104 datasets. Gene ontology analysis showed that preoperative CRT significantly enriched the immune response in LARC tissues. Moreover, gene set enrichment analysis revealed six significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways associated with downregulated genes, including mismatch repair (MMR) genes, in LARC tissues after CRT in all three cohorts. Radiation also induced apoptosis and downregulated various MMR system-related genes in three colorectal cancer cells. One patient with LARC showed a change in microsatellite instability (MSI) status after CRT, as demonstrated by the loss of MMR protein and PCR for MSI. Moreover, CRT significantly increased tumor mutational burden in LARC tissues. CIBERSORT analysis revealed that the proportions of M2 macrophages and CD8 T cells were significantly increased after CRT in both the RNA-seq dataset and GSE94104. Notably, preoperative CRT increased various immune biomarker scores, such as the interferon-γ signature, the cytolytic activity and the immune signature. Taken together, our findings demonstrated that neoadjuvant CRT modulated the immune-related characteristics of LARC, suggesting that neoadjuvant CRT may enhance the responsiveness of LARC to immunotherapy.

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Promoter methylation data from genomic DNA in patient with rectal cancer

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Project description:Preoperative chemoradiotherapy (CRT) followed by surgery has been proved to improve esophageal squamous cell carcinoma (ESCC) patientsM-bM-^@M-^Y 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 mRNA markers for ESCC CRT-response prediction through gene expression analyses. Gene expression analyses were performed on pretreatment cancer biopsies from 28 ESCCs who received neoadjuvant CRT and surgery and 10 normal esophageal epithelia using Affymetrix U133 Plus 2.0 arrays.

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