Abstract
Increasing evidence supports that proteasome activator subunit (PSME) genes play an indispensable role in multiple tumors. The diverse expression patterns, prognostic value, underlying mechanism, and the role in the immunotherapy of PSME genes in gastric cancer (GC) have yet to be fully elucidated. We systematically demonstrated the functions of these genes in GC using various large databases, unbiased in silico approaches, and experimental validation. We found that the median expression levels of all PSME genes were significantly higher in GC tissues than in normal tissues. Our findings showed that up-regulated PSME1 and PSME2 expression significantly correlated with favorable overall survival, post-progression survival, and first progression survival in GC patients. The expression of PSME1 and PSME2 was positively correlated with the infiltration of most immune cells and the activation of anti-cancer immunity cycle steps. Moreover, GC patients with high PSME1 and PSME2 expression have higher immunophenoscore and tumor mutational burden. In addition, a receiver operating characteristic analysis suggested that PSME3 and PSME4 had high diagnostic performance for distinguishing GC patients from healthy individuals. Moreover, our further analysis indicated that PSME genes exert an essential role in GC, and the present study indicated that PSME1 and PSME2 may be potential prognostic markers for enhancing survival and prognostic accuracy in GC patients and may even act as potential biomarkers for GC patients indicating a response to immunotherapy. PSME3 may serve as an oncogene in tumorigenesis and may be a promising therapeutic target for GC. PSME4 had excellent diagnostic performance and could serve as a good diagnostic indicator for GC.
Highlights
Gastric cancer (GC) is one of the most prevalent solid tumors and the second most frequent cause of cancer-related deaths worldwide (Bray et al, 2018; Cavatorta et al, 2018)
These results demonstrate that a high expression of PSME1 and PSME2 is positively related with favorable overall survival (OS), first progression survival (FPS), and post-progression survival (PPS) in gastric cancer (GC) patients with most clinicopathological features, while high expression levels of these genes are significantly correlated with poor prognosis in GC patients with 5-FU-based adjuvant treatment
The findings indicated that PSME1 expression level may affect the prognosis of GC patients, partly because it impacts the degree of immune infiltration, and that PSME1 could act as a potential biomarker for the response to immunotherapy of GC patients
Summary
Gastric cancer (GC) is one of the most prevalent solid tumors and the second most frequent cause of cancer-related deaths worldwide (Bray et al, 2018; Cavatorta et al, 2018). The recent development of immune checkpoint blockpoint blockade (ICB) therapy has revolutionized the field of cancer therapy. ICB permits that the patient’s immune system recognizes and attacks cancer cells, mounting an effective antitumoral response that contributes to eradicate the disease. Only up to two thirds of cancer patients benefit from immunotherapy, highlighting the need of discovering new biomarkers to select patients suitable for ICB (Jiang et al, 2018). Given the limited therapeutic approaches and the lack of prognostic and therapeutic biomarkers for advanced GC, it is imperative to search for novel biomarkers that can inform about the immunotherapy response of the patient, guiding clinicians to choose the most suitable therapy strategy, and to help researchers to develop new therapeutic targets for GC
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