Natural killer cell-related prognosis signature predicts immune response in colon cancer patients

Abstract

Background: Natural killer (NK) cells are crucial components of the innate immune system that fight tumors and viral infections. Patients with colorectal cancer (CRC) have a poor prognosis, and immunotherapeutic tools play a key role in the treatment of CRC.Methods: Public data on CRC patients was collected from the TCGA and the GEO databases. Tissue data of CRC patients were collected from Guangxi Medical University Affiliated Cancer Hospital. An NK-related prognostic model was developed by the least absolute shrinkage and selection operator (LASSO) and Cox regression method. Validation data were collected from different clinical subgroups and an external independent validation cohort to verify the model’s accuracy. In addition, multiple external independent immunotherapy datasets were collected to further examine the value of NK-related risk scores (NKRS) in the prediction of immunotherapy response. Potential biological functions of key genes were examined by methods of cell proliferation, apoptosis and Western blotting.Results: A novel prognostic model for CRC patients based on NK-related genes was developed and NKRS was generated. There was a significantly poorer prognosis among the high-NKRS group. Based on immune response prediction, patients with low NKRS may be more suitable for immunotherapy and they are more sensitive to immunotherapy. The proliferation rate of CRC cells was significantly reduced and apoptosis of CRC cells was increased after SLC2A3 was knocked down. SLC2A3 was also found to be associated with the TGF-β signaling pathway.Conclusion: NKRS has potential applications for predicting prognostic status and response to immunotherapy in CRC patients. SLC2A3 has potential as a therapeutic target for CRC.

SLC2A3 promotes tumor progression through lactic acid-promoted TGF-β signaling pathway in oral squamous cell carcinoma

“…In this study, we identified the regulatory axis of SLC2A3/LA/TGF-β/SMAD in oral squamous cell carcinoma (OSCC). Initially, our western blot analysis revealed a one-way regulatory relationship from SLC2A3 to TGF-β, echoing findings in colorectal cancer research by Li [35]. In contrast, other studies reported SLC2A3 being regulated by TGF-β, which triggers JNK/ ATF2 binding to its promoter region [36].…”

Integrated analysis of single-cell and bulk RNA-sequencing reveals a novel signature based on NK cell marker genes to predict prognosis and immunotherapy response in gastric cancer

“…Previous study have reported the predictive value of NK signatures in gastrointestinal cancer. This NK signature consists of SLC2A3 and POU2F2, can predict both the prognosis of colon cancer patients and the efficacy of immunotherapy 22 . However, this study has relatively little research on the relationship between NK signatures and the tumor microenvironment and gene mutations.…”

Integration of single-cell sequencing and bulk RNA-seq to identify and develop a prognostic signature related to colorectal cancer stem cells

“…Activated NK cells are well-known for their ability to inhibit the development and progression of CRC by leveraging their tumoricidal functions. Immunotherapies directed at NK cells significantly contribute to improving the prognostic evaluation for CRC patients 112 , 113 . Despite the effectiveness of NK cells in eliminating CSCs, the potential for CSCs to evade immune responses remains a concern in the context of NK cell-based therapies 114 .…”