COMPARATIVE ANALYSIS OF GENE EXPRESSION IN CACHEXIA AND NON-CACHEXIA MICE MODELS OF COLORECTAL CANCER USING SINGLE-CELL RNA SEQUENCING

Published in 08/11/2023 - ISBN: 978-65-272-0061-1

Paper Title
COMPARATIVE ANALYSIS OF GENE EXPRESSION IN CACHEXIA AND NON-CACHEXIA MICE MODELS OF COLORECTAL CANCER USING SINGLE-CELL RNA SEQUENCING
Authors
  • IAGO DIOGO SILVEIRA
  • Amanda Piveta Schnepper
  • VICTàRIA LARISSA SCHIMIDT CAMARGO
  • Jakeline Santos Oliveira
  • Sarah Santiloni Cury
  • Ana Luiza Labbate Bonaldo
  • Caio Fernando Ferreira Mussatto
  • Robson Carvalho
Modality
Poster
Subject area
RNA and transcriptomics
Publishing Date
08/11/2023
Country of Publishing
Brazil | Brasil
Language of Publishing
en-US
Paper Page
https://www.even3.com.br/anais/xmeeting2023/643345-comparative-analysis-of-gene-expression-in-cachexia-and-non-cachexia-mice-models-of-colorectal-cancer-using-singl
ISBN
978-65-272-0061-1
Keywords
cancer mouse models, cachexia, malignant cells
Summary
Cancer-associated cachexia (CC) is a multifactorial syndrome characterized by weight loss and is marked by skeletal muscle and adipose tissue wasting and systemic inflammation. Cachexia is responsible for the death of at least 20% of all cancer patients and is prevalent in 50-61% of colorectal cancer patients. The use of colorectal cancer mouse models is an indispensable approach for investigating treatments for cancer cachexia. The literature has established the CT26 tumor model, derived from colon carcinoma cells, as one of the most used and well-established models for studying cachexia. This model promotes a pro-inflammatory response, which plays a critical role in muscle and adipose tissue wasting, and the tumor secretes cachexia-inducing factors (CIFs) as those found in humans. Emerging technologies like single-cell RNA sequencing (scRNA-seq) have enabled us to gain a more comprehensive and in-depth understanding of the cellular makeup of tumor microenvironments, providing novel insights into regulatory mechanisms. In this study, we used scRNA-seq data (GSE121861) to compare the gene expression profiles of malignant single cells from two mouse models: CT26 (4,479 cells, 2 samples), which induces cachexia, and MC38 (1,310 cells, 2 samples), a non-cachexia model. The scRNA-seq data were processed in Seurat 4.3.0 package (R 4.2.1), including quality control, PCA, clustering, cell type annotation, selection of malignant cells, integration of malignant cells and gene expression analysis. Cell markers from literature were used to annotate malignant cells. The malignant cells from both CT26 and MC38 models were integrated and re-clustered. Next, we identified genes that marked each cluster and differentially expressed genes between each cluster compared to all other cluster were analyzed using the EnrichR online tool (https://maayanlab.cloud/Enrichr/) for ontology (GO Biological Process 2021) and pathways (Reactome 2022). We found that out of the eight clusters examined, clusters 3 and 7 had a predominance of CT26 cells, while the other clusters had a homogeneous cell distribution between the models. Interestingly, cluster 7 showed enrichment for the inflammatory response and activation of the innate immune system pathway, which may be related to cachexia in CT26 model. In conclusion, we found that the gene expression profiles of malignant cells from CT26 and MC38 cell lines, derived from the same tissue, are similar. However, the CT26 model promotes a greater pro-inflammatory response pathway that may be linked to cachexia. Future research into tumor microenvironment and CIFs can provide further insight into the interaction between malignant and immune cells in cancer cachexia models, leading to the development of more effective therapies to combat this debilitating condition.
Title of the Event
X-Meeting / BSB 2023
City of the Event
Curitiba
Title of the Proceedings of the event
X-Meeting presentations
Name of the Publisher
Even3
Means of Dissemination
Meio Digital

How to cite

SILVEIRA, IAGO DIOGO et al.. COMPARATIVE ANALYSIS OF GENE EXPRESSION IN CACHEXIA AND NON-CACHEXIA MICE MODELS OF COLORECTAL CANCER USING SINGLE-CELL RNA SEQUENCING.. In: X-Meeting presentations. Anais...Curitiba(PR) Campus da indústria, 2023. Available in: https//www.even3.com.br/anais/xmeeting2023/643345-COMPARATIVE-ANALYSIS-OF-GENE-EXPRESSION-IN-CACHEXIA-AND-NON-CACHEXIA-MICE-MODELS-OF-COLORECTAL-CANCER-USING-SINGL. Access in: 06/06/2026

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