High Expression of Bloom Syndrome Helicase is a Key Factor for Poor Prognosis and Advanced Malignancy in Patients with Pancreatic Cancer: A Retrospective Study.

Abstract

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 < 0.001). 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.

• Authors: Chuan Lan, Yo-Ichi Yamashita, Hiromitsu Hayashi, Shigeki Nakagawa, Katsunori Imai, Kosuke Mima, Takayoshi Kaida, Takashi Matsumoto, Masataka Maruno, Zhao Liu, Xiyu Wu, Feng Wei, Hideo Baba
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 29 Issue 6 Pg. 3551-3564 (Jun 2022) ISSN: 1534-4681 [Electronic] United States
• PMID: 35419757 (Publication Type: Journal Article)
• Copyright: © 2022. Society of Surgical Oncology.

Chemical References

• RNA, Messenger

Topics

• Bloom Syndrome
• Humans
• Male
• Pancreatic Neoplasms
• Prognosis
• RNA, Messenger (genetics)
• Retrospective Studies
• Pancreatic Neoplasms