Significance of Gene Polymorphism and Gene Expression of BACE2 in Swedish Patients with Colorectal Cancer.

IF 2.5 3区医学 Q3 ONCOLOGY

Oncology Pub Date : 2024-08-14 DOI:10.1159/000540887

Jan Dimberg, Levar Shamoun, Kristin Af Geijerstam, Kalle Landerholm, Dick Wågsäter

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引用次数: 0

Abstract

Introduction: β-site amyloid precursor protein (APP) cleaving enzyme 2 (BACE2) cleaves APP which is ubiquitously expressed in a variety of cell types including cancer cells. BACE2 can process APP in several ways and appears to be involved in the pathogenesis of cancer. Our purpose was to assess the association of mRNA expression and genetic polymorphism of BACE2 in colorectal cancer (CRC) susceptibility and its association to clinicopathological factors in Swedish patients with CRC.

Methods: A total of 720 CRC patients and 470 healthy controls were genotyped for BACE2 gene polymorphism rs2012050, using TaqMan single nucleotide polymorphism (SNP) assays based on polymerase chain reaction. Reverse transcription quantitative PCR was used to investigate the BACE2 gene expression in 192 CRC tissue and 181 paired normal tissue.

Results: Assessing clinicopathological factors, we noted that carrying of T allele in C/T and C/T+T/T was significantly associated with a protective role against disseminated cancer and higher lymph node status. Moreover, individuals carrying T/T genotype were significantly more likely to have poorly differentiated cancer. Follow-up data for patients in poorly differentiated cancer and the Kaplan-Meier analysis showed that the cancer-specific survival curves differed between C/C and C/T+T/T for the BACE2 gene polymorphism and that the carriers of the genotype C/C were associated with more favorable prognosis. We found no significant differences in the genotypic frequencies between the patients and healthy controls. BACE2 mRNA level was significantly 2.2-fold upregulated in CRC tissue when compared to noncancerous tissue. A higher BACE2 mRNA level was observed in smaller tumors and in rectal cancer when compared to colon cancer.

Conclusion: In patients with CRC, our results indicate BACE2 rs2012050 as a useful potential predictor of poor differentiation, disseminated cancer and lymph node status and that the BACE2 mRNA expression is associated to tumor size and cancer location.

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瑞典结直肠癌患者 BACE2 基因多态性和基因表达的意义

导言：β位点淀粉样前体蛋白（APP）裂解酶2（BACE2）能裂解APP，而APP在包括癌细胞在内的多种细胞类型中普遍表达。BACE2 能以多种方式处理 APP，似乎与癌症的发病机制有关。我们的目的是评估 BACE2 的 mRNA 表达和遗传多态性与结直肠癌（CRC）易感性的关系，以及与瑞典 CRC 患者临床病理因素的关系：方法：使用基于聚合酶链反应的 TaqMan 单核苷酸多态性 (SNP) 检测法，对 720 名 CRC 患者和 470 名健康对照者进行 BACE2 基因多态性 rs2012050 的基因分型。采用逆转录定量 PCR 技术研究了 192 例 CRC 组织和 181 例配对正常组织中 BACE2 基因的表达情况：在评估临床病理因素时，我们注意到 C/T 和 C/T+T/T 中的 T 等位基因携带者对扩散癌和较高淋巴结状态有明显的保护作用。此外，携带T/T基因型的人患分化不良癌症的几率明显更高。对分化不良癌症患者的随访数据和 Kaplan-Meier 分析表明，BACE2 基因多态性的 C/C 和 C/T+T/T 之间的癌症特异性生存曲线不同，基因型 C/C 携带者的预后更佳。我们发现患者与健康对照组的基因型频率无明显差异。与非癌组织相比，BACE2 mRNA水平在CRC组织中明显上调2.2倍。与结肠癌相比，在较小的肿瘤和直肠癌中观察到更高的 BACE2 mRNA 水平：我们的研究结果表明，在 CRC 患者中，BACE2 rs2012050 是分化不良、扩散癌和淋巴结状态的有效潜在预测因子，而且 BACE2 mRNA 的表达与肿瘤大小和癌症位置有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Oncology 医学-肿瘤学

CiteScore

6.00

自引率

2.90%

发文量

审稿时长

6-12 weeks

期刊介绍： Although laboratory and clinical cancer research need to be closely linked, observations at the basic level often remain removed from medical applications. This journal works to accelerate the translation of experimental results into the clinic, and back again into the laboratory for further investigation. The fundamental purpose of this effort is to advance clinically-relevant knowledge of cancer, and improve the outcome of prevention, diagnosis and treatment of malignant disease. The journal publishes significant clinical studies from cancer programs around the world, along with important translational laboratory findings, mini-reviews (invited and submitted) and in-depth discussions of evolving and controversial topics in the oncology arena. A unique feature of the journal is a new section which focuses on rapid peer-review and subsequent publication of short reports of phase 1 and phase 2 clinical cancer trials, with a goal of insuring that high-quality clinical cancer research quickly enters the public domain, regardless of the trial’s ultimate conclusions regarding efficacy or toxicity.