脂质滴相关基因作为诊断和预后生物标记物在头颈部鳞状细胞癌中的潜力。
The potential of lipid droplet-associated genes as diagnostic and prognostic biomarkers in head and neck squamous cell carcinoma.
发表日期:2023 Mar 28
作者:
Yu-Ting Bai, Xin Wang, Ming-Jing He, Ji-Rong Xie, Xiao-Jie Chen, Gang Zhou
来源:
BIOMEDICINE & PHARMACOTHERAPY
摘要:
脂滴(LDs)和脂滴相关基因(LD-AGs)在头颈部鳞状细胞癌(HNSCC)中的作用还不清楚。本研究旨在研究HNSCC中的LDs并鉴定对HNSCC患者诊断和预后至关重要的LD-AGs。对HNSCC和正常细胞株进行了油红O染色以显示LDs。使用生物信息学分析在HNSCC中发现了具有诊断和预后意义的LD-AGs。HNSCC细胞株中的LDs堆积与正常细胞株相比增加(P<0.05)。基于TCGA平台,在HNSCC中发现53个不同表达的基因,其中34个上调和19个下调(P<0.05)。然后,53个基因被证明在脂质代谢和LDs中功能富集。其中,34个基因具有高预测能力,AUC值>0.7。在这些诊断基因的34个基因中,6个基因(AUP1、CAV1、CAV2、CAVIN1、HILPDA和SQLE)与HNSCC患者的总生存期存在联系(P<0.05)。使用单变量和多变量cox比例风险模型进一步发现了重要的预后因素AUP1、CAV1、CAV2和SQLE(P<0.05)。CAV2和SQLE的蛋白表达在HNSCC组织中显著增加,与正常组织相比(P<0.05)。最后,敲低这四个LD-AGs之一可以分别减少LDs的积累量。LDs积累的增加是HNSCC的一个特征,AUP1、CAV1、CAV2和SQLE是具有诊断和预后潜力的差异性表达的LD-AGs。版权所有© Bentham Science Publishers;有任何疑问,请发送电子邮件至epub@benthamscience.net。
The role of lipid droplets (LDs) and lipid droplet-associated genes (LD-AGs) remains unclear in head and neck squamous cell carcinoma (HNSCC). This study aimed to investigate LDs in HNSCC and identify LD-AGs essential for the diagnosis and prognosis of HNSCC patients.The LDs in the HNSCC and normal cell lines were stained with oil red O. Bioinformatic analysis was used to find LD-AGs in HNSCC that had diagnostic and prognostic significance.LDs accumulation was increased in HNSCC cell lines compared with normal cell lines (P<0.05). Fifty-three differentially expressed genes, including 34 upregulated and 19 downregulated, were found in HNSCC based on the TCGA platform (P<0.05). Then, 53 genes were proved to be functionally enriched in lipid metabolism and LDs. Among them, with an AUC value > 0.7, 34 genes demonstrated a high predictive power. Six genes (AUP1, CAV1, CAV2, CAVIN1, HILPDA, and SQLE) out of 34 diagnostic genes were linked to overall survival in patients with HNSCC (P<0.05). The significant prognostic factors AUP1, CAV1, CAV2, and SQLE were further identified using the univariate and multivariate cox proportional hazard model (P<0.05). The protein expression of CAV2 and SQLE was significantly increased in the HNSCC tissue compared to normal tissues (P<0.05). Finally, the knockdown of the four LD-AGs decreased LDs accumulation, respectively.Increased LDs accumulation was a hallmark of HNSCC, and AUP1, CAV1, CAV2, and SQLE were discovered as differentially expressed LD-AGs with diagnostic and prognostic potential in HNSCC.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.