Role of LATS1/2 in Prognosis of Advanced Gastric Cancer and Its Relationship With the Tumor Immune Microenvironment

Yixian Guo; Xu Liu; Danhua Xu; Chen Huang; Zeyu Wang; Xiang Xia; Chunchao Zhu; Jia Xu; Zizhen Zhang; Yanying Shen; Wenyi Zhao; Gang Zhao

doi:10.3389/fonc.2020.01406

Role of LATS1/2 in Prognosis of Advanced Gastric Cancer and Its Relationship With the Tumor Immune Microenvironment

Front Oncol. 2020 Aug 25:10:1406. doi: 10.3389/fonc.2020.01406. eCollection 2020.

Authors

Yixian Guo¹, Xu Liu¹, Danhua Xu¹, Chen Huang¹, Zeyu Wang¹, Xiang Xia¹, Chunchao Zhu¹, Jia Xu¹, Zizhen Zhang¹, Yanying Shen², Wenyi Zhao¹, Gang Zhao¹

Affiliations

¹ Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
² Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Abstract

Background: Gastric cancer (GC) remains a refractory cancer particularly in Eastern Asia. Large tumor suppressor kinases 1/2 (LATS1/2) are core members of the Hippo pathway. The role of LATS1/2 in the prognosis of different subtypes of advanced gastric cancer and its relationship with the tumor immune microenvironment in GC remain unknown. Exploring the role of LATS1/2 in GC might provide potential immunotherapeutic approaches for treating GC. Methods: Four hundred and ninety surgically resected primary GC samples were assessed for LATS1/2, CD8, FOXP3, and CD163. Correlations between LATS1/2 expression and immune-related markers were investigated and the prognoses of patients with different GC subtypes were analyzed. Results: CD8 and CD163 appeared to be favorable and adverse prognostic factors, respectively. LATS1/2 and FOXP3 did not predict patients' overall survival. However, in microsatellite-stable GC patients, high LATS1/2 and FOXP3 expression and low CD8 expression predicted poor prognoses. Furthermore, high LATS1/2 expression was significantly correlated with decreased CD8 and increased FOXP3. Combined analysis of LATS1/2, CD8, and FOXP3 had better prognostic accuracy than did each marker individually. Conclusions: Different biological molecules can predict the prognoses of different types of GC patients. LATS1/2, core kinases in the Hippo pathway, are closely related to CD8 and FOXP3. Further understanding the mechanisms of LATS1/2 in CD8⁺ T cells and FOXP3⁺ Treg cells provides further theoretical basis and potential targets for GC immunotherapy.

Keywords: CD163; CD8; FOXP3; LATS1/2; gastric cancer; microsatellite stability; prognosis.