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
Research background

Serum amyloid A1 (SAA1) is regarded as an important regulator in the immune network. Recently, SAA1 was reported to regulate the development of some cancers, and it may function as a biomarker for some cancers.

Research motivation

SAA1 is a potential biomarker in some cancers, but its expression and function in hepatocellular carcinoma (HCC) are still unclear.

Research objectives

The project was designed to determine the expression level of SAA1 in HCC and to analyze the association between SAA1 expression and prognosis of HCC patient and its potential regulation on the immune network.

Research methods

GEPIA web-based analytical tool was subjected to evaluate the expression of SAA1 in HCC. The patients from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) were sub-grouped according to the median expression level of SAA1. Then, the Kaplan-Meier portal was used to analyze the survival curve of the high or low SAA1 expression groups. UALCAN tool was used to evaluate the expression of SAA1 in different tumor grades, stages, and TP53 mutation or not. The CIBERSORT method was subjected to test the correlation between SAA1 expression and immune infiltration score in HCC. TISIDB integrated portal was conducted to reveal the association between SAA1 level and the tumor-infiltrating lymphocytes. GSE125336 dataset was subjected to analyze the SAA1 level according to the anti-PD1 response. Gene set enrichment analysis method was subjected to analyze the enriched signaling pathways based on SAA1 in HCC. The co-expression genes of SAA1 was subjected to Metascape to evaluate the hub genes. These hub genes were subjected to GEPIA and Kaplan-Meier to analyze the expression and overall survival.

Research results

SAA1 level was downregulated in the liver tumor, and the lower expression could function as a prognostic biomarker in overall survival, progression-free survival, and disease-specific survival of HCC. Besides, the SAA1 expression level was closely associated with tumor grades and patient stages. More interestingly, the HCC patients with TP53 mutation showed a lower expression of SAA1. SAA1 could act as a good prognostic marker in HCC patients without hepatitis infection. SAA1 expression was positively correlated with the immune infiltration score and tumor-infiltrating lymphocytes. Low SAA1 expression was negatively correlated with anti-immune signaling, including cytokine-cytokine receptor interaction, natural killer cell-mediated cytotoxicity, and antigen processing and presentation. CXCL2 and CCL23 were identified as the hub genes that interacted with SAA1 and acted as prognostic markers for HCC.

Research conclusions

SAA1 expression is low in HCC, and its expression is closely associated with the progression of HCC. Besides, SAA1 can act as a poor prognostic biomarker for HCC patients. More interestingly, SAA1 is closely involved in the regulation of the immune infiltrating process.

Research perspectives

In this study, SAA1 was identified as a negative regulator for HCC, and its expression might be a poor prognostic biomarker for HCC patients. Interestingly, the SAA1 expression was closely related to the tumor-infiltrating immune cells network. However, these findings were based on the expression levels. SAA1 is a secreted protein from the liver, and the secreted levels could be much more practical clinically, especially in the prognosis analysis.