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SMPDL3B 通过促进 M2 巨噬细胞浸润促进胃腺癌的进展。

SMPDL3B contributes to gastric adenocarcinoma cells progression by promoting the infiltration of M2 macrophages.

机构信息

Department of Rheumatology and Immunology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China.

Department of Oncology, Tianjin Union Medical Center, Nankai University, Tianjin, China.

出版信息

Turk J Med Sci. 2023 Oct 4;53(6):1635-1647. doi: 10.55730/1300-0144.5732. eCollection 2023.

DOI:10.55730/1300-0144.5732
PMID:38813495
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10760593/
Abstract

BACKGROUND/AIM: The common disease gastric adenocarcinoma (GAC) has a high morbidity and mortality, so there is an urgent need for research to explore new diagnostic markers and therapeutic targets. This investigation was carried out to investigate the expression of sphingomyelin phosphodiesterase acid-like 3b (SMPDL3B) in GAC and its effects on tumor progression.

MATERIALS AND METHODS

Samples were collected from patients who underwent radical gastrectomy from January 2021 to December 2022. Along with the normal gastric epithelial cell lines GES-1 and SGC-7901, the AGS, MGC-803, and MSN-45 human gastric cancer cell lines were used to confirm SMPDL3B expression. RT-qPCR, Western blot, immunohistochemical, cell proliferation, assay of wound healing, transwell migration assay, invasion assay, flow cytometry, and immune evaluation experiments were carried out.

RESULTS

SMPDL3B was found to be substantially expressed in GAC, and this condition has a bad prognosis. By establishing SMPDL3B knockdown and overexpression of GAC cell lines, this study confirmed that SMPDL3B promoted tumor cell proliferation, migration, and invasion. Additional bioinformatics research revealed a connection between SMPDL3B and immune cell infiltration in the GAC immunological microenvironment, which enhanced tumor cell proliferation by promoting the infiltration content of M2 macrophages.

CONCLUSION

This study determined the function of SMPDL3B for the clinical diagnosis, prediction, and novel management of GAC.

摘要

背景/目的:常见疾病胃腺癌(GAC)发病率和死亡率高,因此迫切需要研究探索新的诊断标志物和治疗靶点。本研究旨在探讨鞘磷脂磷酸二酯酶酸性样 3b(SMPDL3B)在 GAC 中的表达及其对肿瘤进展的影响。

材料与方法

收集 2021 年 1 月至 2022 年 12 月行根治性胃切除术患者的标本。同时采用正常胃上皮细胞系 GES-1 和 SGC-7901,AGS、MGC-803 和 MSN-45 人胃癌细胞系,证实 SMPDL3B 表达。进行 RT-qPCR、Western blot、免疫组化、细胞增殖、划痕愈合试验、Transwell 迁移试验、侵袭试验、流式细胞术和免疫评估实验。

结果

发现 SMPDL3B 在 GAC 中大量表达,且该情况预后不良。通过建立 SMPDL3B 敲低和过表达的 GAC 细胞系,本研究证实 SMPDL3B 促进肿瘤细胞增殖、迁移和侵袭。进一步的生物信息学研究揭示了 SMPDL3B 与 GAC 免疫微环境中免疫细胞浸润之间的联系,通过促进 M2 巨噬细胞的浸润含量来促进肿瘤细胞增殖。

结论

本研究确定了 SMPDL3B 在 GAC 的临床诊断、预测和新的管理中的功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d9d/10760593/acca0b5d3c0a/turkjmedsci-53-6-1635f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d9d/10760593/42dce7950307/turkjmedsci-53-6-1635f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d9d/10760593/0c28fca48c3d/turkjmedsci-53-6-1635f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d9d/10760593/058bd34037d6/turkjmedsci-53-6-1635f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d9d/10760593/d1d1ec296d1f/turkjmedsci-53-6-1635f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d9d/10760593/a2f28a674baf/turkjmedsci-53-6-1635f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d9d/10760593/acca0b5d3c0a/turkjmedsci-53-6-1635f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d9d/10760593/42dce7950307/turkjmedsci-53-6-1635f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d9d/10760593/0c28fca48c3d/turkjmedsci-53-6-1635f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d9d/10760593/058bd34037d6/turkjmedsci-53-6-1635f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d9d/10760593/d1d1ec296d1f/turkjmedsci-53-6-1635f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d9d/10760593/a2f28a674baf/turkjmedsci-53-6-1635f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d9d/10760593/acca0b5d3c0a/turkjmedsci-53-6-1635f6.jpg

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本文引用的文献

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Effect of Charlson Comorbidity Index and Treatment Strategy on Survival of Elderly Patients After Endoscopic Submucosal Dissection for Gastric Adenocarcinoma: A Multicenter Retrospective Study.高龄患者胃腺癌内镜黏膜下剥离术后生存的 Charlson 共病指数及治疗策略的影响:一项多中心回顾性研究。
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SMPDL3B Predicts Poor Prognosis and Contributes to Development of Acute Myeloid Leukemia.
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EMT and Cancer Cell Stemness Associated With Chemotherapeutic Resistance in Esophageal Cancer.上皮-间质转化和癌细胞干性与食管癌化疗耐药性相关
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