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DGAT1 表达促进卵巢癌进展,并与不良预后相关。

DGAT1 Expression Promotes Ovarian Cancer Progression and Is Associated with Poor Prognosis.

机构信息

Department of Obstetrics and Gynecology, Changhai Hospital, Navy Medical University, Shanghai, China.

Department of Urology, Chinese People's Liberation Army(PLA) General Hospital/PLA Medical School, Beijing, China.

出版信息

J Immunol Res. 2021 May 14;2021:6636791. doi: 10.1155/2021/6636791. eCollection 2021.

DOI:10.1155/2021/6636791
PMID:34095320
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8141271/
Abstract

BACKGROUND

Ovarian cancer is the most fatal gynecological malignancy. Owing to its insidious onset, rapid development, and poor prognosis, ovarian cancer is the fifth most common cause of death in women. Although immunotherapy-related drugs, such as Olaparib, can alleviate ovarian cancer progression, there are no remarkable breakthroughs for its effective treatment. It is considered that the transformation of normal cells to cancerous ones involves "recoding" of certain metabolic pathways. Diacylglycerol O-acyltransferase 1 (DGAT1) can synthesize triglycerides by transferring acyl-CoA to diacylglycerol, which plays a key role in lipid synthesis. However, the role of DGAT1 in ovarian cancer is not yet elucidated.

MATERIALS AND METHODS

We analyzed the correlation between DGAT1 and ovarian cancer staging, grading, vascular invasion, and prognosis by collating the information of ovarian cancer specimens from The Cancer Genome Atlas (TCGA) database. Furthermore, the effects of DGAT1 expression on proliferation, migration, invasion, and tumor growth were studied using ovarian cancer cell lines. GSEA was used to analyze the KEGG pathways and biological function enriched because of DGAT1 expression in ovarian cancer.

RESULTS

The expression of DGAT1 was elevated in advanced ( = 0.0432), poorly differentiated ( = 0.0148), and vascular invaded ( = 0.0002) ovarian cancer specimens. Prognosis among patients with high expression of DGAT1 was poor. After DGAT1 expression was interfered, proliferation, migration, invasion, colony forming, and tumor growth of ovarian cancer cells were inhibited. In addition, GSEA showed that DGAT1 may be involved in the immune process.

CONCLUSION

DGAT1 expression is associated with the clinical phenotype of ovarian cancer. We suggest that DGAT1 has potential implications in the treatment of ovarian cancer.

摘要

背景

卵巢癌是最致命的妇科恶性肿瘤。由于其隐匿性发病、快速发展和预后不良,卵巢癌是女性第五大常见死亡原因。尽管免疫治疗相关药物,如奥拉帕利,可以缓解卵巢癌的进展,但对于其有效的治疗方法尚无显著突破。人们认为正常细胞向癌细胞的转化涉及某些代谢途径的“重编码”。二酰基甘油 O-酰基转移酶 1(DGAT1)可以通过将酰基辅酶 A 转移到二酰基甘油来合成甘油三酯,在脂质合成中起着关键作用。然而,DGAT1 在卵巢癌中的作用尚不清楚。

材料和方法

我们通过整理来自癌症基因组图谱(TCGA)数据库的卵巢癌标本信息,分析了 DGAT1 与卵巢癌分期、分级、血管浸润和预后的相关性。此外,还使用卵巢癌细胞系研究了 DGAT1 表达对增殖、迁移、侵袭和肿瘤生长的影响。GSEA 用于分析由于 DGAT1 表达在卵巢癌中富集的 KEGG 途径和生物学功能。

结果

DGAT1 的表达在晚期(=0.0432)、低分化(=0.0148)和血管侵袭(=0.0002)的卵巢癌标本中升高。高表达 DGAT1 的患者预后较差。干扰 DGAT1 表达后,卵巢癌细胞的增殖、迁移、侵袭、集落形成和肿瘤生长受到抑制。此外,GSEA 表明 DGAT1 可能参与免疫过程。

结论

DGAT1 的表达与卵巢癌的临床表型相关。我们认为 DGAT1 可能对卵巢癌的治疗具有潜在意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b051/8141271/790a8e88b946/JIR2021-6636791.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b051/8141271/a11d1b5b1641/JIR2021-6636791.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b051/8141271/adfd03ce779c/JIR2021-6636791.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b051/8141271/bbd469ec778c/JIR2021-6636791.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b051/8141271/790a8e88b946/JIR2021-6636791.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b051/8141271/a11d1b5b1641/JIR2021-6636791.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b051/8141271/adfd03ce779c/JIR2021-6636791.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b051/8141271/bbd469ec778c/JIR2021-6636791.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b051/8141271/790a8e88b946/JIR2021-6636791.004.jpg

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