Prognostic role of myeloid-derived tumor-associated macrophages at the tumor invasive margin in gastric cancer with liver metastasis (GCLM): a single-center retrospective study

Zeyu Wang; Zhongyi Dong; Gang Zhao; Bo Ni; Zi-Zhen Zhang

doi:10.21037/jgo-22-530

Prognostic role of myeloid-derived tumor-associated macrophages at the tumor invasive margin in gastric cancer with liver metastasis (GCLM): a single-center retrospective study

J Gastrointest Oncol. 2022 Jun;13(3):1340-1350. doi: 10.21037/jgo-22-530.

Authors

Zeyu Wang^#¹, Zhongyi Dong^#¹, Gang Zhao¹, Bo Ni¹, Zi-Zhen Zhang¹

Affiliation

¹ Department of Gastrointestinal Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

^# Contributed equally.

Abstract

Background: Liver metastasis is one of the important factors leading to poor prognosis of gastric cancer. According to the classic "seed soil theory", it is speculated that the liver microenvironment at the invasion margin of gastric cancer liver metastases (GCLM) may have a crucial impact on tumor progression. However, few studies had stated the correlation between the patients' prognosis and the densities of stromal cells infiltrating into the invasive margin, where our retrospective study designed to identify the role of infiltrating macrophages on the prognosis of GCLM as a reliable supplement of predictive tumor markers.

Methods: The material consisted of a group of 72 gastric cancer (GC) patients with liver metastasis diagnosed from February 2015 and December 2020. The CD68⁺, CD206⁺, and Clec4f⁺ macrophages in their specimens were counted by immunohistochemistry (IHC), and the analysis area was the invasive margin of metastatic lesions. Clinical data were collected retrospectively. Overall survival (OS) was calculated from the date of initial diagnosis to the date of last follow-up or death. Survival analyses were performed using the Kaplan-Meier method and log-rank test. Multivariate Cox regression was performed to asses impact of macrophages on OS.

Results: The expression of CD206 could indicate the prognosis of patients with GCLM, and patients with high expression of CD206 had worse prognoses (P=0.0002). Univariate and multivariate analyses showed that CD206 was an independent risk factor for prognosis (HR 5.276, 95% CI: 1.730-16.089, P=0.003).

Conclusions: The CD206⁺ myeloid-derived tumor associated macrophages (TAMs) may predict whether patients could benefit from R1 resection of liver-metastatic lesions, which has important theoretical significance and practical value for accurately evaluating the clinical prognosis of patients with GCLM and guiding clinical treatment.

Keywords: Gastric cancer with liver metastasis (GCLM); invasion margin; prognosis; tumor-associated macrophages (TAMs).