Published online Mar 15, 2024. doi: 10.4251/wjgo.v16.i3.945
Peer-review started: November 25, 2023
First decision: December 7, 2023
Revised: December 25, 2023
Accepted: January 30, 2024
Article in press: January 30, 2024
Published online: March 15, 2024
Processing time: 108 Days and 2.9 Hours
Gastric cancer (GC) is a highly aggressive malignancy with a heterogeneous nature, which makes prognosis prediction and treatment determination difficult. Inflammation is now recognized as one of the hallmarks of cancer and plays an important role in the aetiology and continued growth of tumours. Inflammation also affects the prognosis of GC patients. Recent reports suggest that a number of inflammatory-related biomarkers are useful for predicting tumour prognosis.
The importance of inflammatory-related biomarkers in predicting the prognosis of GC patients is still unclear.
We established a novel three-gene prognostic signature that may be useful for predicting the prognosis and personalizing treatment decisions of GC patients.
We downloaded the mRNA expression profiles and corresponding clinical data of patients with GC from a public database. Then, we constructed a prognostic signature comprising three differentially expressed genes (DEGs) related to the inflammatory response. We employed univariate and multivariate Cox regression analyses to evaluate the prognosis of patients with GC from the GEO cohort independently and validated the stability and reliability of the findings. Furthermore, we analysed the associations between prognostic gene expression and immune infiltrate types and between prognostic gene expression and chemotherapeutic sensitivity.
A prognostic model consisting of three inflammatory-related genes (MRPS17, GUF1, and PDK4) was constructed. Independent prognostic analysis revealed that the risk score was a separate prognostic factor in GC patients. According to the risk score, GC patients were stratified into high- and low-risk groups, and patients in the high-risk group had significantly worse prognoses according to age, sex, TNM stage and Lauren type. Consensus clustering identified three subtypes of inflammation that could predict GC prognosis more accurately than traditional grading and staging. Finally, the study revealed that patients in the low-risk group were more sensitive to certain drugs than were those in the high-risk group, indicating a link between inflammation-related genes and drug sensitivity.
We identified a novel signature consisting of three inflammatory response-related genes that could precisely predict the prognosis of patients with GC. However, the specific underlying mechanism of inflammatory response-related genes and tumour immunity in GC is still unclear and deserves further study. Taken together, our work will help shed light on the role of these genes in tumorigenesis, particularly in the areas of immune response, tumour microenvironment and drug resistance, which are critical for the development of personalized cancer therapies.
We believe that this powerful prognostic signature could help improve the risk stratification of GC patients, provide a more effective assessment for clinical management and provide new therapeutic targets for the treatment of these patients.