Researchers from The University of Texas MD Anderson Cancer Center have conducted a comprehensive study that deepens the understanding of the tumor microenvironment's evolution during gastric cancer progression. The study, published in Cancer Cell, highlights the connection between multicellular communities and clinical outcomes, as well as a potential therapeutic target.
Gastric adenocarcinoma, a highly lethal cancer, is known for its inherent treatment resistance. However, the cellular and molecular mechanisms involved in the progression of this cancer from early pre-cancerous stages to tumor formation and metastasis remain poorly understood. This study sheds light on the dynamic changes that occur in immune and stromal cell subsets throughout gastric cancer development.
Led by Dr. Linghua Wang, the researchers employed single-cell RNA sequencing (scRNA-seq) to analyze 68 gastric adenocarcinoma samples representing various disease stages, along with normal tissue and peripheral blood samples. By characterizing the diverse immune and stromal cell populations within the tumor microenvironment, the team identified exploitable targets for modulating the microenvironment.
The study introduced the concept of "ecotypes," referring to multicellular communities or collections of cell states within an individual tumor sample. Six unique ecotypes dominated by specific immune and stromal cell states were identified. Two ecotypes (EC3 and EC6) were found to correlate with different histological, genomic, and clinical features of primary gastric adenocarcinomas. Patients with EC6 tumors exhibited more aggressive disease and significantly shorter survival compared to those with EC3 tumors.
A potential therapeutic target, SDC2, was identified in stromal cells, particularly in cancer-associated fibroblasts. Overexpression of SDC2 in stromal cells was associated with aggressive disease, advanced stages, and unfavorable survival outcomes. Notably, elevated SDC2 expression was consistently observed in stromal cells across various cancer types.
The findings of this study have been shared with the research community through the Wang Lab's online Single-Cell Research Portal, facilitating further collaboration and exploration in the field.