关键词: Liver hepatocellular carcinoma NTRK Trk bioinformatics immunohistochemistry

来  源:   DOI:10.1177/11795549231180840   PDF(Pubmed)

Abstract:
UNASSIGNED: The neurotrophic tyrosine kinase (NTRK) gene family includes NTRK1, NTRK2, and NTRK3, which encode tropomyosin receptor kinases TrkA, TrkB, and TrkC, respectively. This study aimed to initially assess the genomic and proteomic profiles of NTRK genes and Trk receptors in liver hepatocellular carcinoma (LIHC).
UNASSIGNED: The ONCOMINE, UALCAN, GEPIA, cBioPortal, FusionGDB, SurvivalMeth, and the Human Protein Atlas databases were searched for NTRK gene expression and protein data in LIHC. Immunohistochemistry was used to detect pan-Trk expression across a commercial microarray containing 96 hepatocellular carcinoma (HCC) and 94 para-cancerous tissue spots. A modified histological score (H-score) with a maximum score of 300 was used to quantify immunohistochemical staining for pan-Trk. Student\'s t- and chi-square tests were the main statistical analyses used.
UNASSIGNED: The transcriptional levels of NTRK genes in LIHC were not significantly different from healthy controls. Using UALCAN and GEPIA, only high expression of NTRK2 was significantly associated with longer disease-free survival (P = 0.004). The alteration frequencies were low (7% in NTRK1, 1.7% in NTRK2, and 2% in NTRK3). The methylation levels of NTRK genes were all significantly different as analyzed by UALCAN; the high-risk group displayed an unfavorable prognosis compared with the low-risk group for NTRK1 (P = 0.033) and NTRK3 (P = 0.005). The median H-score of pan-Trk in HCC and para-cancerous tissues was not statistically different (186.31 ± 23.86 and 192.38 ± 21.06, P = 0.065). No differences were observed in clinicopathological features of HCC with the median H-score for pan-Trk expression (p > 0.05). The survival rate of patients with pan-Trk expression was also not significantly different.
UNASSIGNED: The alteration frequency was low in NTRK genes, including gene fusion and methylation levels. Therefore, pan-Trk expression in HCC tissue has limited value in clinicopathological features and prognosis.
摘要:
神经营养酪氨酸激酶(NTRK)基因家族包括NTRK1,NTRK2和NTRK3,它们编码原肌球蛋白受体激酶TrkA,TrkB,和TrkC,分别。本研究旨在初步评估肝细胞癌(LIHC)中NTRK基因和Trk受体的基因组和蛋白质组学特征。
ONCOMINE,UALCAN,GEPIA,cBioPortal,FusionGDB,SurvivalMeth,在LIHC中搜索NTRK基因表达和蛋白质数据。免疫组织化学用于检测包含96个肝细胞癌(HCC)和94个癌旁组织斑点的商业微阵列中的pan-Trk表达。使用最大评分为300的改良组织学评分(H评分)来定量pan-Trk的免疫组织化学染色。学生t检验和卡方检验是使用的主要统计分析。
LIHC中NTRK基因的转录水平与健康对照没有显着差异。使用UALCAN和GEPIA,只有NTRK2的高表达与更长的无病生存期显著相关(P=0.004)。改变频率较低(NTRK1为7%,NTRK2为1.7%,NTRK3为2%)。通过UALCAN分析,NTRK基因的甲基化水平均存在显着差异;与NTRK1(P=0.033)和NTRK3(P=0.005)的低危组相比,高危组的预后不良。pan-Trk在HCC和癌旁组织中的中位H评分无统计学差异(186.31±23.86和192.38±21.06,P=0.065)。HCC的临床病理特征与pan-Trk表达的中位数H评分无差异(p>0.05)。pan-Trk表达患者的存活率也无明显差别。
NTRK基因的改变频率较低,包括基因融合和甲基化水平。因此,pan-Trk在HCC组织中的表达对临床病理特征和预后的影响有限。
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