Dataset Information

Identification of immunotherapy and chemotherapy-related molecular subtypes in colon cancer by integrated multi-omics data analysis.

ABSTRACT:

Background

Colon cancer is a highly heterogeneous disease, and identifying molecular subtypes can provide insights into deregulated pathways within tumor subsets, which may lead to personalized treatment options. However, most prognostic models are based on single-pathway genes.

Methods

In this study, we aimed to identify three clinically relevant subtypes of colon cancer based on multiple signaling pathways-related genes. Integrative multi-omics analysis was used to explain the biological processes contributing to colon cancer aggressiveness, recurrence, and progression. Machine learning methods were employed to identify the subtypes and provide medication guidance for distinct subtypes using the L1000 platform. We developed a robust prognostic model (MKPC score) based on gene pairs and validated it in one internal test set and three external test sets. Risk-related genes were extracted and verified by qPCR.

Results

Three clinically relevant subtypes of colon cancer were identified based on multiple signaling pathways-related genes, which had significantly different survival state (Log-Rank test, p<0.05). Integrative multi-omics analysis revealed biological processes contributing to colon cancer aggressiveness, recurrence, and progression. The developed MKPC score, based on gene pairs, was robust in predicting prognosis state (Log-Rank test, p<0.05), and risk-related genes were successfully verified by qPCR (t test, p<0.05). An easy-to-use web tool was created for risk scoring and therapy stratification in colon cancer patients, and the practical nomogram can be extended to other cancer types.

Conclusion

In conclusion, our study identified three clinically relevant subtypes of colon cancer and developed a robust prognostic model based on gene pairs. The developed web tool is a valuable resource for researchers and clinicians in risk scoring and therapy stratification in colon cancer patients, and the practical nomogram can be extended to other cancer types.

SUBMITTER: Zhu J

PROVIDER: S-EPMC10067602 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Identification of immunotherapy and chemotherapy-related molecular subtypes in colon cancer by integrated multi-omics data analysis.

Zhu Jie J Kong Weikaixin W Huang Liting L Bi Suzhen S Jiao Xuelong X Zhu Sujie S

Frontiers in immunology 20230320

<h4>Background</h4>Colon cancer is a highly heterogeneous disease, and identifying molecular subtypes can provide insights into deregulated pathways within tumor subsets, which may lead to personalized treatment options. However, most prognostic models are based on single-pathway genes.<h4>Methods</h4>In this study, we aimed to identify three clinically relevant subtypes of colon cancer based on multiple signaling pathways-related genes. Integrative multi-omics analysis was used to explain the b ...[more]

PMID: 37020539

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Project description:BackgroundBeing the most widely used biomarker for immunotherapy, the microsatellite status has limitations in identifying all patients who benefit in clinical practice. It is essential to identify additional biomarkers to guide immunotherapy. Aberrant DNA methylation is consistently associated with changes in the anti-tumor immune response, which can promote tumor progression. This study aims to explore immunotherapy biomarkers for colon cancers from the perspective of DNA methylation.MethodsThe related data (RNA sequencing data and DNA methylation data) were obtained from The Cancer Genome Atlas (TCGA) and UCSC XENA database. Methylation-driven genes (MDGs) were identified through the Pearson correlation analysis. Unsupervised consensus clustering was conducted using these MDGs to identify distinct clusters of colon cancers. Subsequently, we evaluated the immune status and predicted the efficacy of immunotherapy by tumor immune dysfunction and exclusion (Tide) score. Finally, The Quantitative Differentially Methylated Regions (QDMR) software was used to identify the specific DNA methylation markers within particular clusters.ResultsA total of 282 MDGs were identified by integrating the DNA methylation and RNA-seq data. Consensus clustering using the K-means algorithm revealed that the optimal number of clusters was 4. It was revealed that the composition of the tumor immune microenvironment (TIME) in Cluster 1 was significantly different from others, and it exhibited a higher level of tumor mutation burdens (TMB) and stronger anti-tumor immune activity. Furthermore, we identified three specific hypermethylation genes that defined Cluster 1 (PCDH20, APCDD1, COCH). Receiver operating characteristic (ROC) curves demonstrated that these specific markers could effectively distinguish Cluster 1 from other clusters, with an AUC of 0.947 (95% CI 0.903-0.990). Finally, we selected clinical samples for immunohistochemical validation.ConclusionIn conclusion, through the analysis of DNA methylation, consensus clustering of colon cancer could effectively identify the cluster that benefit from immunotherapy along with specific methylation biomarkers.

Project description:BackgroundLung adenocarcinoma (LUAD) is a heterogeneous tumor characterized by diverse genetic and molecular alterations. Developing a multi-omics-based classification system for LUAD is urgently needed to advance biological understanding.MethodsData on clinical and pathological characteristics, genetic alterations, DNA methylation patterns, and the expression of mRNA, lncRNA, and microRNA, along with somatic mutations in LUAD patients, were gathered from the TCGA and GEO datasets. A computational workflow was utilized to merge multi-omics data from LUAD patients through 10 clustering techniques, which were paired with 10 machine learning methods to pinpoint detailed molecular subgroups and refine a prognostic risk model. The disparities in somatic mutations, copy number alterations, and immune cell infiltration between high- and low-risk groups were assessed. The effectiveness of immunotherapy in patients was evaluated through the TIDE and SubMap algorithms, supplemented by data from various immunotherapy groups. Furthermore, the Cancer Therapeutics Response Portal (CTRP) and the PRISM Repurposing dataset (PRISM) were employed to investigate new drug treatment approaches for LUAD. In the end, the role of SLC2A1 in tumor dynamics was examined using RT-PCR, immunohistochemistry, CCK-8, wound healing, and transwell tests.ResultsBy employing multi-omics clustering, we discovered two unique cancer subtypes (CSs) linked to prognosis, with CS2 demonstrating a better outcome. A strong model made up of 17 genes was created using a random survival forest (RSF) method, which turned out to be an independent predictor of overall survival and showed reliable and impressive performance. The low-risk group not only had a better prognosis but also was more likely to display the "cold tumor" phenotype. On the other hand, individuals in the high-risk group showed a worse outlook and were more likely to respond positively to immunotherapy and six particular chemotherapy medications. Laboratory cell tests demonstrated that SLC2A1 is abundantly present in LUAD tissues and cells, greatly enhancing the proliferation and movement of LUAD cells.ConclusionsThorough examination of multi-omics data offers vital understanding and improves the molecular categorization of LUAD. Utilizing a powerful machine learning system, we highlight the immense potential of the riskscore in providing individualized risk evaluations and customized treatment suggestions for LUAD patients.

Dataset Information

Identification of immunotherapy and chemotherapy-related molecular subtypes in colon cancer by integrated multi-omics data analysis.

Background

Methods

Results

Conclusion

Publications

Identification of immunotherapy and chemotherapy-related molecular subtypes in colon cancer by integrated multi-omics data analysis.

Similar Datasets

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