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基因改变与5-氨基酮戊酸在肺腺癌脑转移瘤切除术中荧光活性的相关性的临床应用

Clinical Application of the Association between Genetic Alteration and Intraoperative Fluorescence Activity of 5-Aminolevulinic Acid during the Resection of Brain Metastasis of Lung Adenocarcinoma.

作者信息

Jeong Hyeon Yeong, Suh Won Jun, Kim Seung Hwan, Nam Taek Min, Jang Ji Hwan, Kim Kyu Hong, Kim Seok Hyun, Kim Young Zoon

机构信息

Division of Cerebrovascular Disease and Department of Neurosurgery, Samsung Changwon Hospital, Sungkyunkwan University of School of Medicine, Changwon 51353, Republic of Korea.

Department of Medicine, Sungkyunkwan University of School of Medicine, Suwon 16419, Republic of Korea.

出版信息

Cancers (Basel). 2023 Dec 23;16(1):88. doi: 10.3390/cancers16010088.

Abstract

The primary objective of this study was to investigate the association of certain genetic alterations and intraoperative fluorescent activity of 5-aminolevulinic acid (ALA) in brain metastasis (BM) of lung adenocarcinoma. A retrospective cohort study was conducted among 72 patients who underwent surgical resection of BM of lung adenocarcinoma at our institute for five years. Cancer cell infiltration was estimated by the intraoperative fluorescent activity of 5-ALA, and genetic alterations were analyzed by next-generation sequencing (NGS). The sensitivity and specificity for detecting cancer cell infiltration using 5-ALA were 87.5% and 96.4%, respectively. Genes associated with cell cycle regulation ( = 0.003) and cell proliferation ( = 0.044) were significantly associated with positive fluorescence activity of 5-ALA in the adjacent brain tissue. Genetic alterations in cell cycle regulation and cell proliferation were also associated with shorter recurrence-free survival ( = 0.013 and = 0.042, respectively) and overall survival ( = 0.026 and = 0.042, respectively) in the multivariate analysis. The results suggest that genetic alterations in cell cycle regulation and cell proliferation are associated with positive fluorescence activity of 5-ALA in the adjacent infiltrative brain tissue and influence the clinical outcome of BM of lung adenocarcinoma.

摘要

本研究的主要目的是调查肺腺癌脑转移(BM)中某些基因改变与5-氨基乙酰丙酸(ALA)术中荧光活性之间的关联。对我院5年间接受肺腺癌BM手术切除的72例患者进行了一项回顾性队列研究。通过5-ALA的术中荧光活性评估癌细胞浸润情况,并通过二代测序(NGS)分析基因改变。使用5-ALA检测癌细胞浸润的敏感性和特异性分别为87.5%和96.4%。与细胞周期调控(P = 0.003)和细胞增殖(P = 0.044)相关的基因与相邻脑组织中5-ALA的阳性荧光活性显著相关。在多变量分析中,细胞周期调控和细胞增殖方面的基因改变也与无复发生存期缩短(分别为P = 0.013和P = 0.042)和总生存期缩短(分别为P = 0.026和P = 0.042)相关。结果表明,细胞周期调控和细胞增殖方面的基因改变与相邻浸润性脑组织中5-ALA的阳性荧光活性相关,并影响肺腺癌BM的临床结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ffa/10778171/d491bb09de24/cancers-16-00088-g001.jpg

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