LCN2 Is a Potential Biomarker for Radioresistance and Recurrence in Nasopharyngeal Carcinoma.
LCN2 Is a Potential Biomarker for Radioresistance and Recurrence in Nasopharyngeal Carcinoma.
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LCN2 是鼻咽癌放射抗性和复发的潜在生物标志物。
DOI：
10.3389/fonc.2020.605777
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发表时间：
2020
影响因子：
4.7
通讯作者：
Tu ZW
中科院分区：
文献类型：
--
作者：
Zhang MX;Wang L;Zeng L;Tu ZW
放射抵抗引起的局部失败是鼻咽癌治疗失败的主要原因之一，可导致肿瘤残留或复发。已知脂质运载蛋白2（LCN 2）在癌症的发生、进展和治疗反应中起重要作用。然而，其在鼻咽癌放射抵抗中的作用尚不清楚。从基因表达Omnibus（GEO）的微阵列数据中筛选与NPC放射抗性相关的候选生物标志物。采用实时荧光定量PCR（RT-qPCR）和Western blotting检测LCN 2在鼻咽癌细胞系中的表达。采用软琼脂集落形成实验和γ H2 AX实验检测LCN 2基因敲低或过表达对鼻咽癌放射敏感性的影响。免疫组化法检测LCN 2在鼻咽癌组织中的表达。分析生存结局。LCN 2和缺氧诱导因子1-α（HIF-1A）之间可能的相关性通过蛋白质印迹和组织芯片进行了检查。LCN 2在鼻咽癌放射抗性细胞系CNE 2 R中高表达。敲低LCN 2通过损害NPC细胞修复DNA损伤或增殖的能力来增强NPC细胞的辐射敏感性，而LCN 2的异位表达赋予NPC细胞额外的辐射抗性。100例鼻咽癌标本的免疫组化分析显示，LCN 2在放射抵抗的鼻咽癌组织中表达显著上调，并与鼻咽癌复发有关。此外，LCN 2和HIF-1A的表达之间的显着相关性被检测到。LCN 2与鼻咽癌的放射抵抗和复发相关，并可能通过与HIF-1A相互作用促进放射抵抗表型的发展。我们的数据表明，LCN 2是预测和克服鼻咽癌放射抗性的一个有前途的靶点。
Radioresistance-induced local failure, which can result in residual or recurrent tumors, remains one of the major causes of treatment failure in nasopharyngeal carcinoma (NPC). Lipocalin 2 (LCN2) is known to play important roles in cancer initiation, progression, and treatment responses. However, its role in the radioresistance of NPC remains unclear. Microarray data from the Gene Expression Omnibus (GEO) was screened for candidate biomarkers relating to the radioresistance of NPC. The expression of LCN2 in NPC cell lines was verified by quantitative real-time PCR (RT-qPCR) and western blotting. The effects of knockdown or overexpression of LCN2 on NPC radiosensitivity were examined using a soft agar colony formation assay and a γH2AX assay. LCN2 expression in NPC specimens was evaluated by immunohistochemistry. Survival outcomes were analyzed. A possible correlation between LCN2 and hypoxia-inducible factor 1-alpha (HIF-1A) was examined by western blotting and a tissue microarray. LCN2 was highly expressed in the radioresistant NPC cell line CNE2R. Knocking down LCN2 enhanced the radiosensitivity of NPC cells by impairing their ability to repair DNA damage or proliferate, while ectopic expression of LCN2 conferred additional radioresistance to NPC cells. Immunohistochemical analysis of 100 NPC specimens revealed that LCN2 expression was significantly upregulated in radioresistant NPC tissues and was associated with NPC recurrence. Furthermore, a significant correlation between the expression of LCN2 and HIF-1A was detected. LCN2 is associated with radioresistance and recurrence in NPC and may facilitate the development of a radioresistant phenotype through interacting with HIF-1A. Our data indicate that LCN2 is a promising target for predicting and overcoming radioresistance in NPC.
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影响因子：
16
作者：
Goetz, DH;Holmes, MA;Strong, RK
通讯作者：
Strong, RK
影响因子：
2
作者：
Horsman MR;Overgaard J
通讯作者：
Overgaard J
影响因子：
4.7
作者：
Lin, Chiao-Wen;Yang, Wei-En;Chien, Ming-Hsien
通讯作者：
Chien, Ming-Hsien
影响因子：
3.4
作者：
Guo, WF;Lin, RX;Wang, SQ
通讯作者：
Wang, SQ
通过蛋白质组学鉴定预测鼻咽癌放疗反应的生物标志物
影响因子：
11.2
作者：
Feng, Xue-Ping;Yi, Hong;Xiao, Zhi-Qiang
通讯作者：
Xiao, Zhi-Qiang