Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2020; 26(35): 5287-5301
Published online Sep 21, 2020. doi: 10.3748/wjg.v26.i35.5287
Immune infiltration-associated serum amyloid A1 predicts favorable prognosis for hepatocellular carcinoma
Wei Zhang, Hui-Fang Kong, Xu-Dong Gao, Zheng Dong, Ying Lu, Jia-Gan Huang, Hong Li, Yong-Ping Yang
Wei Zhang, Hui-Fang Kong, Xu-Dong Gao, Zheng Dong, Ying Lu, Jia-Gan Huang, Yong-Ping Yang, Center for Diagnosis and Research of Liver Tumor, Fifth Medical Center of People's Liberation Army General Hospital, Beijing 100191, China
Hong Li, Department of Infectious Diseases, the Affiliated Hospital of Guizhou Medical University, Guiyang 550001, Guizhou Province, China
Author contributions: Zhang W and Kong HF conducted data analysis, wrote the manuscript, and contributed equally to this study; Gao XD and Huang JG conducted the literature research and data collection; Dong Z, Lu Y and Li H discussed the results and statistical analysis; Yang YP designed the study and revised the manuscript.
Supported by Guizhou Provincial Natural Science Foundation, No. 2020-1Y299.
Institutional review board statement: This study was approved by the Ethical committee of the Fifth Medical Center of People's Liberation Army General Hospital.
Conflict-of-interest statement: All authors have nothing to declare.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Yong-Ping Yang, MD, Chief Doctor, Center for Diagnosis and Research of Liver Tumor, Fifth Medical Center of People's Liberation Army General Hospital, No. 100 West Sihuan Road, Fengtai District, Beijing 100191, China.
Received: May 10, 2020
Peer-review started: May 10, 2020
First decision: July 29, 2020
Revised: August 3, 2020
Accepted: August 13, 2020
Article in press: August 13, 2020
Published online: September 21, 2020

Serum amyloid A1 (SAA1) is an acute-phase protein involved in acute or chronic hepatitis. Its function is still controversial. In addition, the effect of the expression of SAA1 and its molecular function on the progression in hepatocellular carcinoma (HCC) is still unclear.


To demonstrate the expression of SAA1 and its effect on the prognosis in HCC and explain further the correlation of SAA1 and immunity pathways.


SAA1 expression in HCC was conducted with The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) in GEPIA tool, and the survival analysis based on the SAA1 expression level was achieved in the Kaplan-Meier portal. The high or low expression group was then drawn based on the median level of SAA1 expression. The correlation of SAA1 and the clinical features were conducted in the UALCAN web-based portal with TCGA-LIHC, including tumor grade, patient disease stage, and the TP53 mutation. The correlation analysis between SAA1 expression and TP53 mutation was subjected to the TCGA portal. The tumor purity score and the immune score were analyzed with CIBERSORT. The correlation of SAA1 expression and tumor-infiltrating lymphocytes was achieved in TISIDB web-based integrated repository portal for tumor-immune system interactions. GSE125336 dataset was used to test the SAA1 expression in the responsive or resistant group with anti-PD1 therapy. Gene set enrichment analysis was applied to evaluate the gene enrichment signaling pathway in HCC. The similar genes of SAA1 in HCC were identified in GEPIA, and the protein-protein interaction of SAA1 was conducted in the Metascape tool. The expression of C-X-C motif chemokine ligand 2, C-C motif chemokine ligand 23, and complement C5a receptor 1 was studied and overall survival analysis in HCC was conducted in GEPIA and Kaplan-Meier portal, respectively.


SAA1 expression was decreased in HCC, and lower SAA1 expression predicted poorer overall survival, progression-free survival, and disease-specific survival. Furthermore, SAA1 expression was further decreased with increased tumor grade and patient disease stage. Also, SAA1 expression was further downregulated in patients with TP53 mutation compared with patients with wild type TP53. SAA1 expression was negatively correlated with the TP53 mutation. Lower SAA1 predicted poorer survival rate, especially in the patients with no hepatitis virus infection, other than those with hepatitis virus infection. Moreover, the SAA1 expression was negatively correlated with tumor purity. In contrast, SAA1 expression was positively correlated with the immune score in HCC, and the correlation analysis between SAA1 expression and tumor-infiltrating lymphocytes also showed a positive correlation in HCC. Decreased SAA1 was closely associated with the immune tolerance of HCC. C-X-C motif chemokine ligand 2 and C-C motif chemokine ligand 23 genes were identified as the hub genes associated with SAA1, which could also serve as favorable prognosis markers for HCC.


SAA1 is downregulated in the liver tumor, and it is closely involved in the progression of HCC. Lower SAA1 expression indicates lower survival rate, especially for those patients without hepatitis virus infection. Lower SAA1 expression also suggests lower immune infiltrating cells, especially for those with immune cells exerting anti-tumor immune function. SAA1 expression is closely associated with the anti-tumor immune pathways.

Keywords: Serum amyloid A1, Hepatocellular carcinoma, Low expression, Prognosis, Hepatitis, Immune pathways

Core Tip: In this study, we identified the downregulation of serum amyloid A1 (SAA1) in hepatocellular carcinoma (HCC). SAA1 expression could predict the favorable prognosis for HCC patients, especially for those patients without hepatitis virus infection. SAA1 expression was closely associated with anti-tumor immune signaling pathways. We also identified two signature genes associated with SAA1, suggesting a favorable prognosis function of SAA1 for HCC patients.