缺氧誘導因子1 α在骨髓增生異常綜合征患者中的表達意義及潛在機制

2019年3月，廣西醫科大學**附屬醫院病理科；廣西醫科大學**附屬醫院腫瘤內科(Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China；Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China) Zhi‐gang Peng老師研究團隊在《Cancer Medicine》上發表論文：

“Expression significance and potential mechanism of hypoxia-inducible factor 1 alpha in patients with myelodysplastic syndromes”

“缺氧誘導因子1 α在骨髓增生異常綜合征患者中的表達意義及潛在機制”

Abstract：

Objective

To investigate the expression level and potential mechanism of hypoxia-inducible factor 1 alpha (HIF-1α) in patients with myelodysplastic syndromes (MDS).

Methods

Immunohistochemistry (IHC) techniques were used to examine the protein expression of HIF-1α in paraffin-embedded myeloid tissues from 82 patients with MDS and 33 controls (patients with lymphoma that is not invading myeloid tissues). In addition, the associations between the protein expression of HIF-1α and clinical parameters were examined. To further investigate the significance of HIF-1α expression in MDS patients, the researchers not only extracted the data about HIF-1α expression from MDS-related microarrays but also analyzed the correlation between the level of HIF-1α expression and MDS. The microRNA (miRNA) targeting HIF-1α was predicted and verified with a dual luciferase experiment.

Results

Immunohistochemistry revealed that the positive expression rate of HIF-1α in the bone marrow of patients with MDS was 90.24%. This rate was remarkably higher than that of the controls (72.73%) and was statistically significant (P < .05), which indicated that HIF-1α was upregulated in the myeloid tissues of MDS patients. For the GSE2779, GSE18366, GSE41130, and GSE61853 microarrays, the average expression of HIF-1α in MDS patients was higher than in the controls. Particularly for the GSE18366 microarray, HIF-1α expression was considerably higher in MDS patients than in the controls (P < .05). It was predicted that miR-93-5p had a site for binding with HIF-1α, and a dual luciferase experiment confirmed that miR-93-5p could bind with HIF-1α.

Conclusion

The upregulated expression of HIF-1α was examined in the myeloid tissues of MDS patients. The presence of HIF-1α (+) suggested an unsatisfactory prognosis for patients, which could assist in the diagnosis of MDS. In addition, miR-93-5p could bind to HIF-1α by targeting, showing its potential to be the target of HIF-1α in MDS.

摘要：

目的

探討缺氧誘導因子1α (HIF-1α)在骨髓增生異常綜合征(MDS)患者中的表達水平及其潛在機制。

方法

免疫組織化學(IHC)技術檢測了82例MDS患者和33例對照(淋巴瘤未侵襲髓樣組織)石蠟包埋髓樣組織中HIF-1α的蛋白表達。此外，研究人員還研究了HIF-1α蛋白表達與臨床參數之間的關系。為了進一步探討HIF-1α表達在MDS患者中的意義，研究人員不僅從MDS相關芯片中提取了HIF-1α表達數據，還分析了HIF-1α表達水平與MDS的相關性。通過雙熒光素酶實驗對靶向HIF-1α的microRNA (miRNA)進行了預測和驗證。

結果

免疫組化結果顯示HIF-1α在MDS患者骨髓中的陽性表達率為90.24%。這一比例顯著高于對照組(72.73%)，差異有統計學意義(P < 0.05)，說明MDS患者髓系組織中HIF-1α表達上調。對于GSE2779、GSE18366、GSE41130和GSE61853微陣列，MDS患者中HIF-1α的平均表達高于對照組。特別是對于GSE18366芯片，HIF-1α在MDS患者中的表達明顯高于對照組(P < 0.05)。預測miR-93-5p具有與HIF-1α結合的位點，雙熒光素酶實驗證實miR-93-5p能夠與HIF-1α結合。

結論

HIF-1α在MDS患者骨髓組織中表達上調。HIF-1α(+)的存在提示患者預后不佳，有助于MDS的診斷。此外，miR-93-5p可以通過靶向與HIF-1α結合，顯示其在MDS中可能成為HIF-1α的靶標。

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