Impact of Caspase3/GSDME-Mediated Pyroptosis on Tumor Immune Microenvironment and Clinical Prognosis Across Multiple Cancers.

Background: Globally, the disease that has the greatest impact on human health and is the most difficult to overcome is cancer (tumor or malignant tumor is another name for it). Cancers currently known to us can arise from almost any organ or tissue in the human body. Its uncontrolled growth pattern and metastasis characteristics are the fundamental reasons for the high mortality rate of cancer and its current incurability. An increasing number of studies have found that pyroptosis, a mode of programmed cell death, may inhibit tumor growth by changing the tumor immune microenvironment (TIME).

Methods: Through a retrospective study, we selected 160 cases of different tumor tissues (including 40 cases each of esophageal cancer, gastric cancer, breast cancer, and cervical cancer), and identified the expression of caspase3/GasderminE in the tumor tissues through immunohistochemical staining and infiltration of tumor-related immune cells. And analyze its relationship with clinical parameters of tumor patients. In addition, we also marked caspase8 and caspase9 among the caspase family members to analyze the main factors upstream of caspase3.

Results: The results showed that the expression level of caspase3/GSDME in different tumor tissues was positively correlated with the infiltration degree of tumor-related immune cells (natural killer cells, CD8+T cells, macrophages, etc). In addition, the expression level of caspase3 was positively correlated with caspase8, but not caspase9.

Summary: The expression levels of caspase3 and GSDME exhibited significant impacts on the survival prognosis of patients with diverse tumors as well as alterations in the immune microenvironment of tumor tissues, demonstrating statistical significance. After Caspase3/GSDME triggers the pyroptosis pathway, it may change the components of the immune microenvironment of tumor tissue, thereby achieving the effect of inhibiting tumors.