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Characterisation of the Expression of Neurotensin and Its Receptors in Human Colorectal Cancer and Its Clinical Implications.
Biomolecules ( IF 4.8 ) Pub Date : 2020-08-05 , DOI: 10.3390/biom10081145
Shengyang Qiu 1, 2, 3 , Stella Nikolaou 1, 2, 3 , Jie Zhu 4 , Peter Jeffery 4 , Robert Goldin 5 , James Kinross 1 , James L Alexander 6 , Shahnawaz Rasheed 1, 2 , Paris Tekkis 1, 2, 3 , Christos Kontovounisios 1, 2, 3
Affiliation  

Introduction: Colorectal Cancer (CRC) accounts for 9% of cancer deaths globally. Hormonal pathways play important roles in some cancers. This study investigated the association of CRC expression of neurotensin (NTS), NTS receptors 1 and 3 (NTSR1 and NTSR3) and clinical outcomes. Methods: A prospective cohort study which quantifies the protein expression of NTS, NTSR1 and NTSR3 in human CRCs using immunohistochemistry. Expression levels were then compared with clinico-pathological outcome including histological grade, overall survival (OS) and disease-free survival (DFS). Results: Sixty-four patients were enrolled with median follow-up of 44.0 months. There was significantly higher expression of NTS in cancer tissue in CRC with higher T stages (p < 0.01), N stages (p = 0.03), and AJCC clinical stages (p = 0.04). There was significantly higher expression of NTS, NTSR1 and NTSR3 in cancer tissue compared to surrounding normal epithelium (median H-score 163.5 vs 97.3, p < 0.01). There was significantly shorter DFS in individuals with CRC with high levels of NTS compared to lower levels of NTS (35.8 months 95% CI 28.7–42.8 months vs 46.4 months 95% CI 42.2–50.5 months, respectively, p = 0.02). Above median NTS expression in cancer tissue was a significant risk factor for disease recurrence (HR 4.10, 95% CI 1.14–14.7, p = 0.03). Discussion: The expression of NTS and its receptors has the potential to be utilised as a predictive and prognostic marker in colorectal cancer for postoperative selection for adjuvant therapy and identify individuals for novel therapies targeting the neurotensinergic pathways. Conclusions: High NTS expression appears to be associated with more advanced CRC and worse DFS.

中文翻译:

大肠癌中神经降压素及其受体表达的特征及其临床意义。

简介:大肠癌(CRC)占全球癌症死亡人数的9%。激素途径在某些癌症中起重要作用。这项研究调查了神经降压素(NTS),NTS受体1和3(NTSR1和NTSR3)的CRC表达与临床结局的关系。方法:一项前瞻性队列研究,采用免疫组织化学方法定量检测人CRC中NTS,NTSR1和NTSR3的蛋白表达。然后将表达水平与临床病理结果进行比较,包括组织学等级,总生存期(OS)和无病生存期(DFS)。结果:64例患者入组,中位随访44.0个月。T期较高的CRC患者癌组织中NTS表达明显升高(p<0.01),N个阶段(p = 0.03)和AJCC临床阶段(p = 0.04)。与周围正常上皮相比,癌组织中NTS,NTSR1和NTSR3的表达明显更高(中位数H评分163.5对97.3,p <0.01)。与低水平的NTS相比,高水平NTS的CRC患者的DFS明显短(分别为35.8个月95%CI 28.7-42.8个月和46.4个月95%CI 42.2-50.5个月,p = 0.02)。癌组织中高于NTS表达中位数是疾病复发的重要危险因素(HR 4.10,95%CI 1.14-14.7,p = 0.03)。讨论区:NTS及其受体的表达可能被用作大肠癌的预测和预后标志物,用于术后辅助治疗的选择和确定针对神经降压能途径的新疗法的个体。结论:高NTS表达似乎与更高级的CRC和较差的DFS有关。
更新日期:2020-08-05
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