神经内分泌肿瘤中生长抑素受体表达与临床结局的关联
Association Between Somatostatin Receptor Expression and Clinical Outcomes in Neuroendocrine Tumors.
作者信息
Qian Zhi Rong, Li Tingting, Ter-Minassian Monica, Yang Juhong, Chan Jennifer A, Brais Lauren K, Masugi Yohei, Thiaglingam Arunthathi, Brooks Nichole, Nishihara Reiko, Bonnemarie Mireille, Masuda Atsuhiro, Inamura Kentaro, Kim Sun A, Mima Kosuke, Sukawa Yasutaka, Dou Ruoxu, Lin Xihong, Christiani David C, Schmidlin Fabien, Fuchs Charles S, Mahmood Umar, Ogino Shuji, Kulke Matthew H
机构信息
From the *Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; †Department of Geriatric Gastroenterology, Chinese PLA General Hospital, Beijing, China; ‡Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA; §Collaborative Innovation Center of Tianjin for Medical Epigenetics, Key Laboratory of Hormone and Development (Ministry of Health), Metabolic Disease Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China; ∥IPSEN Bioscience Inc, Global Drug Discovery Department, Cambridge, MA; ¶IPSEN Innovation, Global Drug Discovery Department, Les Ulis, France; Departments of #Biostatistics, and **Epidemiology, Harvard T.H. Chan School of Public Health, ††Massachusetts General Hospital, ‡‡Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, §§Department of Radiology, Massachusetts General Hospital, and ∥∥Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
出版信息
Pancreas. 2016 Nov;45(10):1386-1393. doi: 10.1097/MPA.0000000000000700.
OBJECTIVE
Somatostatin receptors (SSTRs), products of gene superfamily SSTR1-5, are commonly expressed in neuroendocrine tumors (NETs). Somatostatin analogs (SSAs) bind to SSTRs and are used as therapeutic agents in patients with advanced NETs. We hypothesized that tumor SSTR expression status would be associated with clinical outcomes in NET.
METHODS
Expression of the 5 SSTRs was evaluated by immunohistochemistry, using tissue microarrays comprising 173 primary NETs, 24 matched metastases, and 22 metastatic NETs from 195 patients. Cox proportional hazards regression analysis was used to assess the association of SSTR expression status (high vs low) with clinical outcomes, adjusting for potential confounders.
RESULTS
High expression of SSTR2 was associated with longer overall survival (OS) in the cohort overall (multivariate hazard ratio, 0.42; 95% confidence interval, 0.21-0.84; P = 0.013). In a subgroup of patients with metastatic small intestine NET treated with SSAs and evaluable for progression, SSTR2 expression was associated with both longer progression-free survival (PFS) and OS. No associations with PFS or OS were observed with expression of other SSTRs.
CONCLUSIONS
Our study demonstrated that expression of SSTR2, but not other SSTRs, is associated with longer OS. In patients treated with SSAs, expression of SSTR2 is associated with longer PFS survival.
目的
生长抑素受体（SSTRs）是基因超家族SSTR1 - 5的产物，在神经内分泌肿瘤（NETs）中普遍表达。生长抑素类似物（SSAs）与SSTRs结合，用作晚期NETs患者的治疗药物。我们假设肿瘤SSTR表达状态与NET的临床结局相关。
方法
采用免疫组织化学方法评估5种SSTRs的表达，使用包含195例患者的173个原发性NETs、24个配对转移灶和22个转移性NETs的组织微阵列。采用Cox比例风险回归分析评估SSTR表达状态（高表达与低表达）与临床结局的相关性，并对潜在混杂因素进行校正。
结果
在整个队列中，SSTR2高表达与更长的总生存期（OS）相关（多变量风险比，0.42；95%置信区间，0.21 - 0.84；P = 0.013）。在接受SSAs治疗且可评估进展的转移性小肠NET患者亚组中，SSTR2表达与更长的无进展生存期（PFS）和OS均相关。未观察到其他SSTRs表达与PFS或OS相关。
结论
我们的研究表明，SSTR2而非其他SSTRs的表达与更长的OS相关。在接受SSAs治疗的患者中，SSTR2表达与更长的PFS生存期相关。
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