Colon cancer. Cancer attacking cell. Colon disease concept
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Genes related to anoikis, a cell death mechanism, have been linked to colorectal cancer. Using scRNA-seq data, researchers identified seven marker genes related to anoikis and divided colorectal cancer (CRC) samples into high/low prognosis risk 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. 

The study was published in Scientific Reports, and the lead authors are Taohui Ding and Zhao Shang of 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 single cell transcriptome dataset GSE221575 of Gene Expression Omnibus (GEO) database and applied it to cell subpopulation type identification, intercellular communication, pseudo time cell trajectory analysis, and receptor ligand expression analysis for CRC. In addition, the RNA transcriptome dataset of The Cancer Genome Atlas (TCGA), and the GSE39582, GSE17536, and GSE17537 datasets of GEO were downloaded and merged into one bulk transcriptome dataset. 

The differentially expressed genes (DEGs) related to anoikis were extracted from these data sets, and key marker genes were obtained after feature selection. 

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

Seven marker genes stood out, including TIMP1, VEGFA, MYC, MSLN, EPHA2, ABHD2, and CD24. The prognostic risk model scoring system built by these seven genes, along with patient clinical data (age, tumor stage, grade), were incorporated to create a nomogram, which predicted the one-, three-, and five-years survival of CRC. 

By using the scoring system, the CRC samples were divided into high/low anoikis-related prognosis risk groups, there are significant differences in immune infiltration, distribution of immune checkpoints, sensitivity to chemotherapy drugs, and efficacy of immunotherapy between these two risk groups. Anoikis genes participate in the differentiation of colorectal cancer tumor cells, promote tumor development, and could 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 declined in recent years, the number of people under 50 years old has increased by 2%. Predictive analysis reveals that by the year 2030, the incidence rate of colon cancer aged 20–34 will increase by 90.0%, while that of rectal cancer will increase by 124.2%. 

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

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