SAAL1, a novel oncogene, is associated with prognosis and immunotherapy in multiple types of cancer

Abstract

Serum amyloid A-like 1 (SAAL1) was recently identified as a novel oncogene in hepatocellular carcinoma (HCC).To explore the potential role of SAAL1 in other cancers, we conducted a pan-cancer analysis of SAAL1 expression and its association with tumor microenvironment (TME) immunological profiles, sensitivity to chemotherapy agents, response to immunotherapy, and patient prognosis. SAAL1 was overexpressed in most malignant tumors in association with poor prognosis. Moreover, its expression was positively correlated with TME-relevant immune and mismatch signatures, immunostimulatory infiltrating cells (CD4 + memory T cells, activated NK cells, M1 macrophages, and cytotoxic CD8 + T cells), microsatellite instability (MSI), tumor mutational burden (TMB), neoantigen load, and immune checkpoint markers (PD-L1, LAG-3 and CTLA-4) in multiple cancers. SAAL1 overexpression was also associated with immunotherapy response and overall survival (OS) in bladder cancer (BLCA) patients who had received anti-PD-L1 treatment. Gene set enrichment analysis (GSEA) further showed significant enrichment of SAAL1 in immune cell signaling, cell cycle, and cell adhesion pathways. Moreover, we detected tumor-specific correlations between SAAL1 expression and either chemoresistance or sensitivity to common chemotherapeutics. Lastly, we showed that SAAL1 silencing suppresses both malignant phenotype and expression of PD-L1 in lung cancer A549 cells in vitro. These findings suggest that SAAL1 contributes to tumorigenesis and antitumor immunity mechanisms in different cancer types, and may thus serve as both a prognostic biomarker and potential target for cancer immunotherapy.

The effects of the prognostic biomarker SAAL1 on cancer growth and its association with the immune microenvironment in lung adenocarcinoma

“…In this research, we confirmed the role of SAAL1 in LAC progression by utilizing bioinformatics analysis and basic research. The findings of the present study reflect the results of Chu et al in HCC [ 8 , 22 ], indicating that SAAL1 could play an oncogenic role in LAC progression. However, this study has the following deficiencies: 1) we should further collect the tissue samples from LAC patients to detect SAAL1 expression levels, and explore the relationship between SAAL1 expression and clinical data of LAC patients to evaluate the clinical values of SAAL1; 2) we will add more LAC cell lines to verify the roles and mechanisms of SALL1 in vivo and in vitro.…”

“…Recent studies have discovered the overexpression of the inflammatory gene SAAL1 in HCC. Furthermore, elevated SAAL1 expression was had something to do with shorter OS in patients with HCC [ 8 , 22 ]. Therefore, inhibition of SAAL1 expression could inhibit the growth and migration ability of HCC cells, impair the AKT/mTOR phosphorylation cascade driven by HGF/MET, and increase the sensitivity of HCC cells to sorafenib and foretinib [ 8 ].…”

Single-Cell Transcriptomics for Unlocking Personalized Cancer Immunotherapy: Toward Targeting the Origin of Tumor Development Immunogenicity

“…High-TMB tumors tend to respond better to immunotherapy due to the creation of more neoantigens. Examples include melanoma, lung, bladder, and head and neck cancers, which also benefit from PD-1 or PD-L1 immune checkpoint inhibitors [14]. However, prostate, pancreatic, and glioblas-toma tumors have a low TMB and tend to be resistant to immunotherapy, suppressing the immune system through various mechanisms such as reduced immune checkpoint expression or immunosuppressive molecule expression [15,16].…”

Serum Amyloid a Predicts Prognosis and Chemotherapy Efficacy in Patients with Advanced Pancreatic Cancer

“… 18 It has also been suggested that high SAA1expression levels in tumor tissues may be associated with resistance to common chemotherapy drugs including paclitaxel, platinum-based drugs, and 5-fluorodeoxyuridine. 19 Given the important role of systemic inflammation in regulating the development and progression of pancreatic cancer, and the influence of SAA1 expression in tumor tissue on the efficacy of chemotherapy, it is important to investigate the prognostic value of circulating SAA in patients with APC received chemotherapy.…”