Novel cell death gene signatures predict colorectal cancer prognosis

Genes related to anoikis, a mechanism of cell death, have been linked to colorectal cancer. Using scRNA-seq data, the researchers identified seven marker genes associated with anoikis and divided colorectal cancer (CRC) samples into high/low prognosis groups. They found significant differences in immune infiltration, distribution of immune checkpoints, sensitivity to chemotherapy drugs, and efficacy of immunotherapy between these two risk groups.

STUDIES was published in Scientific Reportsand lead authors are Taohui Ding and Zhao Shang from China’s Jiangxi Medical College, Nanchang University.

Resistance to anoikis among cancer cells improves metastasis and survival. Anoikis genes are known to play a role in the differentiation of colorectal cancer tumor cells and promote tumor development.

These researchers downloaded the GSE221575 single cell transcriptome dataset of the Gene Expression Omnibus (GEO) database and applied it to cell subpopulation type identification, intercellular communication, pseudo-time cell trajectory analysis, and expression analysis. of receptor ligand for CRC. Additionally, the RNA transcriptome datasets of The Cancer Genome Atlas (TCGA) and GEO datasets GSE39582, GSE17536, and GSE17537 were downloaded and merged into a large transcriptome dataset.

Anoikis-related differentially expressed genes (DEGs) were extracted from these datasets, and top marker genes were obtained after feature selection.

A clinical prognosis prediction model was constructed based on marker genes and the predictive effect was analyzed. Then, gene pathway analysis, immune infiltration analysis, immunosuppressive score analysis, drug sensitivity analysis, and immunotherapy efficacy based on key marker genes were performed for the model. The team used single-cell datasets to determine the anoikis activity of the cells and analyzed the cell DEGs based on the score to identify genes involved in anoikis and extracted disease-related DEGs from the dataset of transcription.

Seven marker genes were identified, incl TIMP1, VEGFA, MYC, MSLN, EPHA2, ABHD2AND CD24. The prognostic risk model scoring system constructed from these seven genes, together with the patient’s clinical data (age, tumor stage, grade), were incorporated to create a nomogram, which predicted one-, three-, and five-year survival. years of KRC.

Using the scoring system, CRC samples were divided into high/low anoikis-related prognosis risk groups, there are significant differences in immune infiltration, immune checkpoint distribution, chemotherapy drug sensitivity, and immunotherapy efficacy between these two risk groups. Anoikis genes participate in the differentiation of colorectal cancer tumor cells, promote tumor development and may predict the prognosis of colorectal cancer.

According to reports, in 2017, the total number of CRC cases in the United States was 13,5430, with approximately 50,260 deaths and a mortality rate of 37.1%. Although the overall incidence rate of CRC has fallen in recent years, the number of people under 50 has increased by 2%. The predictive analysis reveals that by 2030, the incidence rate of colon cancer at age 2034 will increase by 90.0%, while that of rectal cancer will increase by 124.2%.

Studies have shown that about 25% of CRC patients experience metastasis at their initial visit, while nearly half of patients eventually experience liver metastases, lung metastases, bone metastases, or brain metastases. Therefore, prevention of cancer metastases is crucial for improving the prognosis of the disease.