AMICA1 is a diagnostic and prognostic biomarker and induces immune cells infiltration by activating cGAS-STING signaling in lung adenocarcinoma

Ziyang Feng; Yan Zhang; Min He; Ying Han; Changjing Cai; Shanshan Liu; Ping Liu; Yihong Chen; Hong Shen; Shan Zeng

doi:10.1186/s12935-022-02517-x

AMICA1 is a diagnostic and prognostic biomarker and induces immune cells infiltration by activating cGAS-STING signaling in lung adenocarcinoma

Cancer Cell Int. 2022 Mar 5;22(1):111. doi: 10.1186/s12935-022-02517-x.

Authors

Ziyang Feng^{1

2}, Yan Zhang³, Min He^{1

2}, Ying Han^{1

2}, Changjing Cai^{1

2}, Shanshan Liu^{1

2}, Ping Liu^{1

2}, Yihong Chen^{1

2}, Hong Shen^{1

2

4}, Shan Zeng^{1

2}

Affiliations

¹ Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
² Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
³ Department of Oncology, Yueyang People's Hospital, Yueyang Hospital Affiliated to Hunan Normal University, Yueyang, 414000, Hunan, China. yanzhang2021@hunnu.edu.cn.
⁴ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.

Abstract

Background: Adhesion molecule interacting with CXADR antigen 1 (AMICA1), also known as Junction Adhesion Molecule Like (JAML), a recently identified member of the JAMs family, plays a critical role in mediating cancer development and immune cells transmigration. However, AMICA1 has never been reported to be related to the genesis, development and immunotherapy effect of lung adenocarcinoma (LUAD). In this research, we investigated the role of AMICA1 in LUAD through bioinformatic analysis and in vitro experiments.

Methods: Bioinformatic analysis from TCGA and GEO databases were used to investigate the expression level of AMICA1 and the correlation between AMICA1 and clinical parameters in LUAD patients. The LinkedOmics database was analyzed to investigate the co-expression network of AMICA1. TIMER and TISIDB databases were used to analyze the correlation between AMICA1 expression and immune infiltration level. Except for bioinformatic analysis, the AMICA1 mRNA (26 patients) and protein level (6 patients) were also detected by real-time PCR and western blot. The infiltration level of CD8⁺ T cells (15 patients) and PD1⁺ T cells (13 patients) were detected by immunohistochemistry. The diagnostic value of AMICA1 was revealed by receiver operating characteristic (ROC) curves. The Spearman correlation coefficient was used to analyze the correlation between AMICA1 expression and CD8⁺ T cells and PD1⁺ T cells infiltration level.

Results: Bioinformatic data from public database and our data showed that AMICA1 was significantly downregulated in LUAD. Decreased AMICA1 expression in LUAD was associated with higher T stage, M stage and pathological stage. Kaplan-Meier survival analysis indicated that patients with low AMICA1 expression had a worse prognosis. ROC curves showed that AMICA1 had high diagnostic accuracy for LUAD patients. Multivariate Cox analysis further displayed that AMICA1 expression level was an independent prognostic factor for LUAD patients. Moreover, the expression of AMICA1 was significantly different in the immune cells subtype and was obviously linked to immune cells infiltration. In vitro experiments suggested that AMICA1 significantly suppressed the proliferation of LUAD cells and played an important role in activating cGAS-STING signaling.

Conclusions: Our study suggested that AMICA1 might function as a diagnostic and prognostic biomarker and significantly suppressed the proliferation of LUAD cells. Besides, AMICA1 is positively correlated with immune cells infiltration in LUAD, and cGAS-STING signaling might play an important role in the process.

Keywords: AMICA1; Bioinformatics; Biomarkers; Immune infiltration; LUAD; cGAS-STING.

Abstract

Grants and funding