Tao Ya, Wang Kun, Chen Zhen, Long Lu, Wu Qiong, Cui Facai, Zhu Lepan, Xiang Manlin, Jiang Yuan, Liang Yunlai, Qiu Shiyang, Xiao Zhiqiang, Yi Bin
Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Clinical Laboratory, Hunan Cancer Hospital, Changsha, Hunan, China.
Oncotarget. 2017 Apr 25;8(17):29383-29394. doi: 10.18632/oncotarget.14725.
In our previous study, five different secretory proteins, including GSN, ADAMTSL4, CALR, PPIA and TXN, have been identified to be associated with the nasopharyngeal carcinoma (NPC) metastasis.In this work, the 5 proteins were further investigated. Bioinformatics analysis suggested that they might play an important role in the process of NPC development.Western blotting analysis showed that all of these 5 targets could be secreted into extracellular by both high metastatic NPC 5-8F cells and non-metastatic NPC 6-10B cells. Except for GSN, the expressions of ADAMTSL4, CALR, PPIA and TXN proteins in extracts of the 5-8F and 6-10B cells were significantly different (P < 0.05). Thus, the expressions of these 4 differentially expressed proteins were further tested in a cohort of NPC tissue specimens. The results indicated that the expression levels of ADAMTSL4 and TXN were highly correlated with the lymph node and distant metastasis (P<0.05) in NPC patients. Moreover, Enzyme-linked immunosorbent assay (ELISA) was used to investigate the concentrations of the ADAMTSL4 and TXN in serum specimens of NPC patients. The results revealed that serum ADAMTSL4 expression level was closely correlated with lymph node metastasis and clinical stage (P<0.05) in NPC patients, and it was able to discriminate metastasis NPC from non-metastasis NPC with a sensitivity of 75.6% and a specificity of 64.7%. The present data show for the first time that the ADAMTSL4 and TXN may be novel and potential biomarkers for predicting the NPC metastasis.Furthermore, the serum ADAMTSL4 could be a potential serum tumor biomarker for prognosis of NPC.
在我们之前的研究中，已鉴定出包括凝溶胶蛋白（GSN）、含血小板反应蛋白基序的解聚蛋白样金属蛋白酶4（ADAMTSL4）、钙网蛋白（CALR）、肽基脯氨酰异构酶A（PPIA）和硫氧还蛋白（TXN）在内的五种不同分泌蛋白与鼻咽癌（NPC）转移相关。在这项工作中，对这5种蛋白进行了进一步研究。生物信息学分析表明，它们可能在NPC发展过程中起重要作用。蛋白质印迹分析表明，这5个靶点均可由高转移性NPC 5-8F细胞和非转移性NPC 6-10B细胞分泌到细胞外。除GSN外，ADAMTSL4、CALR、PPIA和TXN蛋白在5-8F和6-10B细胞提取物中的表达存在显著差异（P<0.05）。因此，在一组NPC组织标本中进一步检测了这4种差异表达蛋白的表达。结果表明，ADAMTSL4和TXN的表达水平与NPC患者的淋巴结转移和远处转移高度相关（P<0.05）。此外，采用酶联免疫吸附测定（ELISA）法检测NPC患者血清标本中ADAMTSL4和TXN的浓度。结果显示，NPC患者血清ADAMTSL4表达水平与淋巴结转移及临床分期密切相关（P<0.05），其区分转移性NPC和非转移性NPC的灵敏度为75.6%，特异性为64.7%。目前的数据首次表明，ADAMTSL4和TXN可能是预测NPC转移的新型潜在生物标志物。此外，血清ADAMTSL4可能是NPC预后的潜在血清肿瘤生物标志物。
