High Expression of Bloom Syndrome Helicase is a Key Factor for Poor Prognosis and Advanced Malignancy in Patients with Pancreatic Cancer: A Retrospective Study
High Expression of Bloom Syndrome Helicase is a Key Factor for Poor Prognosis and Advanced Malignancy in Patients with Pancreatic Cancer: A Retrospective Study
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DOI：
10.1245/s10434-022-11500-9
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发表时间：
2022-04-13
影响因子：
3.7
通讯作者：
Baba, Hideo
中科院分区：
文献类型：
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作者：
Lan, Chuan;Yamashita, Yo-ichi;Baba, Hideo
Bloom综合征解旋酶（Bloom syndrome helicase，BLM）在多种肿瘤中过表达，其过表达可能导致基因组不稳定。本研究的目的是确定BLM表达在胰腺癌中的功能。方法采用公开数据集分析BLM mRNA表达与胰腺癌预后的关系。总体而言，182例胰腺癌患者接受根治性切除术在我们的机构入组。通过免疫组织化学（IHC）评价BLM表达。我们通过小干扰RNA探讨了BLM对胰腺癌细胞增殖、侵袭、迁移和化疗耐药性的影响，并使用基因集富集分析进行了通路分析。结果BLM mRNA在肿瘤组织中的表达明显高于正常组织，并对总生存期和无复发生存期有影响。通过IHC验证了相同的结果。多变量分析显示，BLM高表达是OS的独立预后不良因素（风险比[HR] 1.678，p = 0.029）。在亚组分析中，年龄越小，BLM高表达对OS的影响越显著（HR 2.27，p = 0.006），男性（HR 2.39，p = 0.002），高癌抗原19-9水平（HR 2.44，p = 0.001），晚期肿瘤分期（HR 2.25，p = 0.001）、淋巴结转移（HR 2.51，p = 0.001）、神经浸润（HR 2.07，p = 0.002）和辅助化疗（HR 2.66，p）。在体外，BLM抑制导致肿瘤增殖，侵袭，迁移和化疗耐药性降低。从机制上讲，BLM表达可能与E2 F1和E2 F2相关。结论BLM表达是胰腺癌患者的一个预后因素，尤其是在晚期恶性肿瘤和接受化疗的患者中。
Background Bloom syndrome helicase (BLM) is overexpressed in multiple types of cancers and its overexpression may induce genomic instability. This study aimed to determine the function of BLM expression in pancreatic cancer. Methods BLM messenger RNA (mRNA) expression was analyzed using public datasets to determine its relationship with pancreatic cancer prognosis. Overall, 182 patients with pancreatic cancer who underwent radical resection at our institution were enrolled. BLM expression was evaluated by immunohistochemistry (IHC). We explored the effect of BLM on the proliferation, invasion, migration, and chemoresistance of pancreatic cancer cells via small-interfering RNAs and performed pathway analysis using gene set enrichment analysis. Results BLM mRNA expression was higher in tumor tissue than in normal tissue and had a prognostic effect on overall survival (OS) and recurrence-free survival. The same results were validated by IHC. Multivariate analysis showed that high BLM expression was an independent poor prognostic factor for OS (hazard ratio [HR] 1.678, p = 0.029). In subgroup analysis, the effect of high BLM expression was more significant on OS in patients with younger age (HR 2.27, p = 0.006), male sex (HR 2.39, p = 0.002), high cancer antigen 19-9 level (HR 2.44, p = 0.001), advanced tumor stage (HR 2.25, p = 0.001), lymph node metastasis (HR 2.51, p = 0.001), nerve invasion (HR 2.07, p = 0.002), and adjuvant chemotherapy (HR 2.66, p ). In vitro, BLM suppression resulted in reduced tumor proliferation, invasion, migration, and chemoresistance. Mechanistically, BLM expression may be associated with E2F1 and E2F2. Conclusion BLM expression is a prognostic factor for patients with pancreatic cancer, especially in those with advanced malignancies and receiving chemotherapy.