A research team at Severance Hospital has found that the amount of ACTA2 (alpha-smooth muscle actin A2) expression, which induces cancer growth, affects the outcome of gastric cancer treatment.

According to data from Statistics Korea in 2021, gastric cancer is one of the most common cancers in Korea, accounting for the fourth most common cancer type (10.8 percent), after colorectal cancer.

The mortality rate for gastric cancer is also high. To improve the treatment performance of gastric cancer, it is necessary to accurately predict the prognosis and establish a treatment plan for each patient.

Previously, treatment plans for gastric cancer patients were based on the expression of HER2 (Human Epidermal growth factor Receptor 2). However, HER2 can only be used to determine the availability of the targeted therapy Herceptin.

While hospitals have also proposed using MSI-H (high microsatellite instability) mutation and EBV (Epstein-Barr virus) to predict the effectiveness of immune checkpoint inhibitors, the incidence rate of both indicators only accounts for 9 percent of gastric cancer patients, making them less effective in clinical practice.

As a result, the team, led by Professor Cheong Jae-ho of the Department of Gastrointestinal Surgery at Severance Hospital, conducted a study on 567 gastric cancer patients enrolled in Yonsei Cancer Center to predict immune checkpoint inhibitor response using ACTA2, which is often observed in tumors with poor prognosis, as a candidate biomarker.

ACTA2 helps establish a tumor microenvironment that influences cancer cell growth.

The team then identified a link between immune response and ACTA2 expression in 108 patients treated with immune checkpoint inhibitors. The immune checkpoint inhibitor response rate in patients with high ACTA2 expression (81 patients) was 25 percent, which was lower than the response rate in patients with low ACTA2 expression (27 patients).

The effectiveness of immune checkpoint inhibitors was also confirmed in patients with MSI-H mutations, where low ACTA2 expression was associated with a higher response rate.

Notably, a digital spatial transcriptome analysis of tumor tissue from nine patients with MSI-H mutations whose cancer cells did not respond to immune checkpoint inhibitors revealed high levels of ACTA2 expression in fibroblasts in their tumor microenvironment.

Digital spatial transcriptome analysis is the latest research method to identify different cell populations in the tumor microenvironment, including cancer cells, in tumor tissue.

“Previously, there were few criteria for predicting the effectiveness of anticancer drugs in gastric cancer patients, which made it difficult to plan treatment, but this study identified a statistically significant biomarker,” Professor Cheong said. “We expect that the research will help the development of gastric cancer drugs that inhibit the expression of ACTA2 in the future.”

The results of the research were published in the Clinical Cancer Research.