Gasdermin D in Different Subcellular Locations Predicts Diverse Progression, Immune Microenvironment and Prognosis in Colorectal Cancer.
Gasdermin D in Different Subcellular Locations Predicts Diverse Progression, Immune Microenvironment and Prognosis in Colorectal Cancer.
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不同亚细胞位置的 Gasdermin D 预测结直肠癌的不同进展、免疫微环境和预后
DOI：
10.2147/jir.s338584
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发表时间：
2021
影响因子：
4.5
通讯作者：
Xu F
中科院分区：
文献类型：
--
作者：
Wang J;Kang Y;Li Y;Sun L;Zhang J;Qian S;Luo K;Jiang Y;Sun L;Xu F
背景细胞凋亡是一种引起免疫反应的细胞死亡。Gasdermin D（GSDMD）作为细胞凋亡的执行者，已成为肿瘤研究的一个重要靶点。然而，GSDMD在不同亚细胞位置表达的临床意义仍不清楚。方法采用免疫组化法检测178例有随访资料的结直肠癌组织中GSDMD的表达。从病例记录中收集关于全身炎症指标的一般数据和信息，并通过显微镜检查审查临床病理参数。免疫组化检测CD 3+、CD 4+、CD 8 + T淋巴细胞、CD 20 + B淋巴细胞和CD 68+巨噬细胞。采用单因素生存分析（Kaplan-Meier法，Log rank检验）和多因素考克斯比例风险模型分析GSDMD对总生存期的影响。结果生存分析显示胞浆GSDMD高表达是独立的预后有利指标（P=0.027），并可提高化疗疗效（P=0.012）。胞浆GSDMD阳性表达提示远处转移的可能性较低（P=0.024），而胞核GSDMD阳性表达预示浸润深度较深（P=0.007）。GSDMD膜表达与肿瘤中心的CD 68+巨噬细胞（P=0.002）和肿瘤浸润前沿的CD 8+淋巴细胞（P=0.007）呈正相关。核GSDMD与肿瘤浸润前沿的CD 68+巨噬细胞（P<0.001）和肿瘤中心的CD 8+淋巴细胞（P=0.069）呈负相关。胞浆型GSDMD与肿瘤中心（P=0.066）和肿瘤浸润前沿（P=0.008）的CD 3+淋巴细胞增多有关。此外，阳性膜GSDMD表明较低的嗜中性粒细胞与淋巴细胞的比例（P=0.013）。结论GSDMD亚细胞定位模式与结直肠癌的进展和免疫反应有关，值得进一步研究。
Background Pyroptosis is a type of cell death that causes an immune reaction. Gasdermin D (GSDMD), as an executor of pyroptosis, has become an attractive target in cancer research. However, the clinical significance of GSDMD expression in different subcellular locations remains unclear. Methods GSDMD was detected by immunohistochemistry in 178 cases of colorectal cancer with follow-up information. General data and information on systemic inflammatory indicators were collected from case records, and the clinicopathological parameters were reviewed by microscopy. CD3+, CD4+, and CD8+ T lymphocytes, CD20+ B lymphocytes, and CD68+ macrophages were detected by immunohistochemistry. Univariate survival analysis (Kaplan–Meier method, Log rank test) and a multivariate Cox proportional hazard model were used to analyze the impact of GSDMD on overall survival. Results Survival analysis showed that high expression of cytoplasmic GSDMD was an independent favorable indicator for prognosis (P=0.027) and improved the efficacy of chemotherapy (P=0.012). Positive cytoplasmic GSDMD expression indicated lower probability of distant metastasis (P=0.024), yet nuclear GSDMD expression predicted deeper infiltration depth (P=0.007). Membranous GSDMD expression positively correlated with CD68+ macrophages in tumor center (P=0.002) and CD8+ lymphocytes in tumor invasive front (P=0.007). However, nuclear GSDMD was negatively related to CD68+ macrophages in tumor invasive front (P<0.001) and CD8+ lymphocytes in tumor center (P=0.069). Cytoplasmic GSDMD was associated with more CD3+ lymphocytes both in tumor center (P=0.066) and tumor invasive front (P=0.008). Moreover, positive membranous GSDMD indicated a lower neutrophil-to-lymphocyte ratio (P=0.013). Conclusion GSDMD subcellular localization patterns are related to CRC progression and immune reaction, and should be investigated in future studies.