Olfactory receptor 51E1 as a novel target for diagnosis in somatostatin receptor-negative lung carcinoids
Olfactory receptor 51E1 as a novel target for diagnosis in somatostatin receptor-negative lung carcinoids
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DOI：
10.1530/jme-13-0144
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发表时间：
2013-12-01
影响因子：
3.5
通讯作者：
Tsolakis, Apostolos V.
中科院分区：
文献类型：
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作者：
Giandomenico, Valeria;Cui, Tao;Tsolakis, Apostolos V.
生长抑素受体（SSTRs）可用于类肺癌（LCs）的诊断和治疗，尽管明确需要其他靶点。本研究旨在探讨嗅觉受体51E1 （OR51E1）是否可能是LCs的潜在靶点。分析了LC细胞株、NCI-H727和NCI-H720中OR51E1的编码序列。采用实时荧光定量PCR技术检测OR51E1转录物在LC细胞株和冷冻标本中的表达情况。在73例典型类癌（tc）、14例非典型类癌（ACs）和11例局部/远处转移瘤的石蜡切片上，通过免疫组织化学方法评估OR51E1、SSTR2、SSTR3和SSTR5的表达，并与octrescan数据进行比较。考虑到细胞区室化（膜vs细胞质）和肿瘤细胞的百分比（50%），免疫组织化学结果在0到3的范围内半定量呈现。结果表明，WT OR51E1转录本在两种LC细胞系中均有表达。OR51E1 mRNA在9 / 12的TCs和7 / 9的ACs中表达（P=NS）。免疫组化检测结果显示，OR51E1、SSTR2、SSTR3和SSTR5分别在85%、71%、25%和39%的tc和86%、79%、43%和36%的ACs中检测到。在79%的tc和86%的ACs中，OR51E1免疫组化评分高于或等于sstr。此外，在所有SSTR亚型缺失的LC病例中，17例tc中有10例和2例ACs中有1例检测到膜OR51E1表达。此外，在6例octrescan阴性LC病变中，有5例检测到较高的OR51E1免疫组化评分。因此，OR51E1在lc中的高表达使其成为sstr阴性肿瘤的潜在新诊断靶点。
Somatostatin receptors (SSTRs) may be used in lung carcinoids (LCs) for diagnosis and therapy, although additional targets are clearly warranted. This study aimed to investigate whether olfactory receptor 51E1 (OR51E1) may be a potential target for LCs. OR51E1 coding sequence was analyzed in LC cell lines, NCI-H727 and NCI-H720. OR51E1 transcript expression was investigated in LC cell lines and frozen specimens by quantitative real-time PCR. OR51E1, SSTR2, SSTR3, and SSTR5 expression was evaluated by immunohistochemistry on paraffin-embedded sections of 73 typical carcinoids (TCs), 14 atypical carcinoids (ACs), and 11 regional/distant metastases and compared with OctreoScan data. Immunohistochemistry results were rendered semiquantitatively on a scale from 0 to 3, taking into account the cellular compartmentalization (membrane vs cytoplasm) and the percentage of tumor cells (50%). Our results showed that WT OR51E1 transcript was expressed in both LC cell lines. OR51E1 mRNA was expressed in 9 out of 12 TCs and 7 out of 9 ACs (P=NS). Immunohistochemically, OR51E1, SSTR2, SSTR3, and SSTR5 were detected in 85, 71, 25, and 39% of TCs and in 86, 79, 43, and 36% of ACs respectively. OR51E1 immunohistochemical scores were higher or equal than those of SSTRs' in79% of TCs and 86% of ACs. Furthermore, in the LC cases where all SSTR subtypes were lacking, membrane OR51E1 expression was detected in 10 out of 17 TCs and 1 out of 2 ACs. Moreover, higher OR51E1 immunohistochemical scores were detected in 5 out of 6 OctreoScan-negative LC lesions. Therefore, the high expression of OR51E1 in LCs makes it a potential novel diagnostic target in SSTR-negative tumors.