A new study led by researchers at The University of Texas MD Anderson Cancer Center provides a deeper understanding of the evolution of the tumor microenvironment during gastric cancer progression. Highlights of the study, published in Cancer Cell, include a link between multicellular communities and clinical outcomes as well as a potential new therapeutic target.
By obtaining single-cell RNA sequencing (scRNA-seq) data from 68 gastric adenocarcinoma samples encompassing various disease stages — including precancerous lesions, localized tumors and distant metastases — along with normal tissue and peripheral blood samples, the team characterized the diverse immune and stromal cell populations within the tumor microenvironment and discovered exploitable targets to modulate the tumor microenvironment.
Various immune and stromal cell subsets formed multicellular communities, or collections of cell states, present in the tumor microenvironment of an individual tumor sample. The research team termed these groups “ecotypes” and identified six unique ecotypes, with each dominated by specific immune and stromal cell states.
A notable discovery is that two ecotypes (EC3 and EC6) correlated with different histological, genomic and clinical features of primary gastric adenocarcinomas. Tumors categorized as EC3 were composed mainly of immune cell subsets, whereas EC6 tumors predominantly included stromal cell subsets. Patients with EC6 tumors had more aggressive disease and significantly shorter survival compared to those with EC3 tumors.
This study identified SDC2 as a potential target worthy of further investigation. Researchers found SDC2 overexpression in stromal cells, especially in cancer-associated fibroblasts, was correlated with aggressive disease and advanced stages, and strongly associated with unfavorable survival outcomes. In addition, SDC2 expression was consistently elevated in stromal cells across various other cancer types, including pancreatic cancer, colorectal cancer, bladder cancer, breast cancer and clear cell renal cell carcinoma.
