Single‐cell profiling reveals tumour cell heterogeneity accompanying a pre‐malignant and immunosuppressive microenvironment in gastric adenocarcinoma

• Published in: Clinical and translational medicine 2023-12, Vol.13 (12), p.e1490-n/a
• Main Authors: Ge, Jie, Xiao, Xiao, Zhou, Haiyan, Tang, Mimi, Bai, Jing, Zou, Xinchen, Zhang, Chunliu, Huang, Changhao, Feng, Xiang, Liu, Ting, Yi, Xin, Xia, Xuefeng, Liu, Heli, Chen, Zihua
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - pathology; Angiogenesis; Cells; Conflicts of interest; Fibroblasts; Gastric cancer; Genomics; Humans; Hypoxia; Immunotherapy; Lymphocytes; Medical prognosis; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Tumor Microenvironment - genetics; Tumors
• ISSN: 2001-1326; 2001-1326
• DOI: 10.1002/ctm2.1490

[...]we classified patients into higher ITH (ITH-H) and lower ITH (ITH-L) groups based on the median of ITH score (Supporting Information Methods), validated by the observation that ITH-H tumours spanned multiple epithelial clusters, which were scarce in ITH-L tumours (Figure 1D and Figure S2C,D). Furthermore, ITH correlated with inferior disease-free survival (DFS) in TCGA-STADs, even after adjusting for confounding factors in multivariate COX regression analysis (Figure 1J,K), suggesting ITH as an independent prognostic factor for recurrence.3 Considering Lauren's subtype, intestinal-type epithelial cells exhibited higher levels of CNV (Figure S2I), consistent with previous reports.4 However, no association was observed between Lauren's subtype and ITH degree either in our cohort or in TCGA-STAD data (Figure S2J,K). MYC was previously reported as a potent regulator in tumour-associated macrophages (TAMs).7,8 Consistently, we detected high expression of MYC and its target genes specific to Mφ-SPP1 (Figure 2E,F and Figure S5F). [...]the targets of MYC were mainly upregulated in Mφ-SPP1 compared with the other two cell types (Figure 2G,H). [...]using a novel scoring method based on cellular similarity of transcriptional profiles, we classified GACs into different ITH groups and comprehensively analysed the associated TME heterogeneity.