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STK11/AMPK 信号通路对食管鳞癌免疫治疗机制的研究

Immunotherapy Mechanism of Esophageal Squamous Cell Carcinoma with the Effect of STK11/AMPK Signaling Pathway.

机构信息

Department of Oncology, Taizhou People's Hospital, Taizhou, 225300 Jiangsu Province, China.

出版信息

Biomed Res Int. 2022 Apr 15;2022:8636527. doi: 10.1155/2022/8636527. eCollection 2022.

Abstract

This study was aimed at exploring the mechanism of serine threonine protein kinase 11 (STK11)/Adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathway after immunotherapy for esophageal squamous cell carcinoma (ESCC), providing basic information for the clinical treatment of ESCC. In this study, tissue specimens from 100 patients with ESCC who underwent surgical treatment in Taizhou People's Hospital (group A) and 20 patients with recurrent or metastatic ESCC who received second-line immunotherapy (group B) were collected. The real-time fluorescent quantitative polymerase chain reaction (PCR) (RT-qPCR) technology was used to detect the expression levels of STK11, interferon- (IFN-), interleukin 6 (IL-6), and vascular endothelial growth factor (VEGF) in the tissues. The immunohistochemical staining was used to detect the positive expression levels (PELs) of STK11 and AMPK in the tissues, and immunofluorescence staining was used to detect the PELs Teff cells (CD3 and CD8), Treg cells (CD4 and FOXP3), and neutrophils (CD68 and CD163). RT-qPCR results showed that the expression levels of STK11 and IFN- in group A were obviously lower, and those of IL-6 and VEGF were much higher in contrast to group B ( < 0.05). The results of immunohistochemical staining showed that the number of STK11- and AMPK-positive staining cells in group A was dramatically less than that in group B ( <0.05). The results of immunofluorescence staining revealed that the number of positive staining cells for Teff cells, Treg cells, and neutrophils in group A was also less dramatically than that in group B ( <0.05). In summary, immunotherapy can play a therapeutic effect on ESCC by regulating STK11/AMPK pathway and immune cell infiltration.

摘要

本研究旨在探讨丝氨酸苏氨酸蛋白激酶 11(STK11)/腺苷 5'-单磷酸激活蛋白激酶(AMPK)信号通路在食管鳞癌(ESCC)免疫治疗后的作用机制,为 ESCC 的临床治疗提供基础信息。本研究收集了泰州市人民医院 100 例接受手术治疗的 ESCC 患者(A 组)和 20 例接受二线免疫治疗的复发性或转移性 ESCC 患者(B 组)的组织标本。采用实时荧光定量聚合酶链反应(PCR)(RT-qPCR)技术检测组织中 STK11、干扰素-(IFN-)、白细胞介素 6(IL-6)和血管内皮生长因子(VEGF)的表达水平。免疫组织化学染色检测组织中 STK11 和 AMPK 的阳性表达率(PEL),免疫荧光染色检测 Teff 细胞(CD3 和 CD8)、Treg 细胞(CD4 和 FOXP3)和中性粒细胞(CD68 和 CD163)的 PEL。RT-qPCR 结果显示,A 组 STK11 和 IFN-的表达水平明显降低,而 IL-6 和 VEGF 的表达水平明显升高(<0.05)。免疫组织化学染色结果显示,A 组 STK11 和 AMPK 阳性染色细胞数明显少于 B 组(<0.05)。免疫荧光染色结果显示,A 组 Teff 细胞、Treg 细胞和中性粒细胞的阳性染色细胞数也明显少于 B 组(<0.05)。综上所述,免疫疗法通过调节 STK11/AMPK 通路和免疫细胞浸润对 ESCC 发挥治疗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e32/9033337/8b2b9a12c6fc/BMRI2022-8636527.001.jpg

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