采用免疫沉淀高效液相色谱法分析口腔鳞状细胞癌的两种不同蛋白质表达谱。
Two different protein expression profiles of oral squamous cell carcinoma analyzed by immunoprecipitation high-performance liquid chromatography.
机构信息
Department of Oral and Maxillofacial Surgery, School of Dentistry, Dental Research Institute, Seoul National University, Seoul, South Korea.
Department of Oral Pathology, College of Dentistry, Institute of Oral Science, Gangneung-Wonju National University, Gangneung, South Korea.
出版信息
World J Surg Oncol. 2017 Aug 8;15(1):151. doi: 10.1186/s12957-017-1213-5.
BACKGROUND
Oral squamous cell carcinoma (OSCC) is one of the most dangerous cancers in the body, producing serious complications with individual behaviors. Many different pathogenetic factors are involved in the carcinogenesis of OSCC. Cancer cells derived from oral keratinocytes can produce different carcinogenic signaling pathways through differences in protein expression, but their protein expression profiles cannot be easily explored with ordinary detection methods.
METHODS
The present study compared the protein expression profiles between two different types of OSCCs, which were analyzed through immunoprecipitation high-performance liquid chromatography (IP-HPLC).
RESULTS
Two types of squamous cell carcinoma (SCC) occurred in a mandibular (SCC-1) and maxillary gingiva (SCC-2), but their clinical features and progression were quite different from each other. SCC-1 showed a large gingival ulceration with severe halitosis and extensive bony destruction, while SCC-2 showed a relatively small papillary gingival swelling but rapidly grew to form a large submucosal mass, followed by early cervical lymph node metastasis. In the histological observation, SCC-1 was relatively well differentiated with a severe inflammatory reaction, while SCC-2 showed severely infiltrative growth of each cancer islets accompanied with a mild inflammatory reaction. IP-HPLC analysis revealed contrary protein expression profiles analyzed by 72 different oncogenic proteins. SCC-1 showed more cellular apoptosis and invasive growth than SCC-2 through increased expression of caspases, MMPs, p53 signaling, FAS signaling, TGF-β1 signaling, and angiogenesis factors, while SCC-2 showed more cellular growth and survival than SCC-1 through the increased expression of proliferating factors, RAS signaling, eIF5A signaling, WNT signaling, and survivin.
CONCLUSIONS
The increased trends of cellular apoptosis and invasiveness in the protein expression profiles of SCC-1 were implicative of its extensive gingival ulceration and bony destruction, while the increased trends of cellular proliferation and survival in the protein profile of SCC-2 were implicative of its rapid growing tumor mass and early lymph node metastasis. These analyses of the essential oncogenic protein expression profiles in OSCC provide important information for genetic counseling or customized gene therapy in cancer treatment. Therefore, protein expression profile analysis through IP-HPLC is helpful not only for the molecular genetic diagnosis of cancer but also in identifying target molecules for customized gene therapy in near future.
背景
口腔鳞状细胞癌（OSCC）是体内最危险的癌症之一，会因个体行为产生严重的并发症。OSCC 的发生涉及多种不同的发病因素。口腔角质细胞来源的癌细胞可通过蛋白表达的差异产生不同的致癌信号通路，但这些蛋白表达谱用常规检测方法不易探测。
方法
本研究通过免疫沉淀高效液相色谱（IP-HPLC）比较了两种不同类型 OSCC 的蛋白表达谱。
结果
两种鳞状细胞癌（SCC）分别发生在下颌（SCC-1）和上颌牙龈（SCC-2），但它们的临床特征和进展截然不同。SCC-1 表现为大的牙龈溃疡伴严重口臭和广泛的骨破坏，而 SCC-2 表现为相对较小的乳头状牙龈肿胀，但迅速生长形成大的黏膜下肿块，随后早期发生颈部淋巴结转移。组织学观察发现，SCC-1 分化较好，炎症反应严重，而 SCC-2 则表现为每个癌巢的浸润性生长伴轻度炎症反应。IP-HPLC 分析显示，72 种不同致癌蛋白的分析结果显示出相反的蛋白表达谱。SCC-1 通过增加半胱天冬酶、MMPs、p53 信号、FAS 信号、TGF-β1 信号和血管生成因子的表达，表现出更多的细胞凋亡和侵袭性生长，而 SCC-2 通过增加增殖因子、RAS 信号、eIF5A 信号、WNT 信号和生存素的表达，表现出更多的细胞生长和存活。
结论
SCC-1 蛋白表达谱中细胞凋亡和侵袭性增加的趋势与其广泛的牙龈溃疡和骨破坏有关，而 SCC-2 蛋白谱中细胞增殖和存活增加的趋势与其快速生长的肿瘤肿块和早期淋巴结转移有关。这些 OSCC 关键致癌蛋白表达谱的分析为癌症的遗传咨询或定制基因治疗提供了重要信息。因此，通过 IP-HPLC 进行蛋白表达谱分析不仅有助于癌症的分子遗传学诊断，而且有助于在不久的将来确定定制基因治疗的靶分子。
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