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半胱天冬酶3/ GasderminE介导的细胞焦亡对多种癌症肿瘤免疫微环境及临床预后的影响

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

作者信息

Huang YuanLi, Liu JinJie, Lin ChunLian, Zhu Qing, Wu LiGao

机构信息

Department of Pathology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, People's Republic of China.

Graduate School of Bengbu Medical University, Bengbu, Anhui, People's Republic of China.

出版信息

Cancer Manag Res. 2024 Nov 26;16:1663-1683. doi: 10.2147/CMAR.S492171. eCollection 2024.

Abstract

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.

摘要

背景

在全球范围内,对人类健康影响最大且最难攻克的疾病是癌症(肿瘤或恶性肿瘤是其别称)。目前我们已知的癌症几乎可起源于人体的任何器官或组织。其不受控制的生长模式和转移特性是癌症高死亡率及当前难以治愈的根本原因。越来越多的研究发现,一种程序性细胞死亡方式——细胞焦亡,可能通过改变肿瘤免疫微环境(TIME)来抑制肿瘤生长。

方法

通过回顾性研究,我们选取了160例不同肿瘤组织(包括食管癌、胃癌、乳腺癌和宫颈癌各40例),通过免疫组化染色鉴定肿瘤组织中半胱天冬酶3/ GasderminE的表达以及肿瘤相关免疫细胞的浸润情况,并分析其与肿瘤患者临床参数的关系。此外,我们还对半胱天冬酶家族成员中的半胱天冬酶8和半胱天冬酶9进行标记,以分析半胱天冬酶3上游的主要因素。

结果

结果显示,不同肿瘤组织中半胱天冬酶3/GSDME的表达水平与肿瘤相关免疫细胞(自然杀伤细胞、CD8 + T细胞、巨噬细胞等)的浸润程度呈正相关。此外,半胱天冬酶3的表达水平与半胱天冬酶8呈正相关,但与半胱天冬酶9无关。

总结

半胱天冬酶3和GSDME的表达水平对多种肿瘤患者的生存预后以及肿瘤组织免疫微环境的改变具有显著影响,具有统计学意义。半胱天冬酶3/GSDME触发细胞焦亡途径后,可能改变肿瘤组织免疫微环境的组成成分,从而达到抑制肿瘤的效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4af/11608053/b01349ca0e76/CMAR-16-1663-g0001.jpg

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