胃癌（GC）是最常見的惡性腫瘤,，在中國癌癥患者中是引發(fā)死亡的首要原因之一。癌癥復(fù)發(fā)的主要因素是治療失敗和胃癌患者手術(shù)切除后5年存活率水平低的主要原因,。因此,，篩選出能預(yù)測復(fù)發(fā)風(fēng)險的潛在生物標志物是解決胃癌患者預(yù)后的關(guān)鍵問題。
近日,，發(fā)表于PLoS One雜志上的一則研究證實hsa-miR-335可作為胃癌預(yù)后的標記物,。研究人員納入74例胃癌患者進行研究，包括31例復(fù)發(fā)和43例無復(fù)發(fā)胃癌患者,。首先,，原發(fā)腫瘤樣本的miRNA芯片和生物信息學(xué)方法分析了miRNA的差異表達。之后,，使用定量PCR驗證出最適合恩的生物標記物,。
結(jié)果確定了12個差異表達的miRNA，其中包括7歌上調(diào)的,、5個下調(diào)的miRNA,。進一步確定has-miR-335是最適合的復(fù)發(fā)預(yù)測因子。hsa-miR-335的高表達,，胃癌復(fù)發(fā)率升高,，生存期降低。此外,，科研人員還評估了hsa-miR-335的幾個致癌信號途徑如P53,、TGF-β，Wnt信號,、ERBB,、mTOR、Toll樣受體等,，這些都是與癌癥轉(zhuǎn)移密切相關(guān)的信號分子,。
總之研究結(jié)果表明,，hsa-miR-335是潛在的預(yù)測復(fù)發(fā)風(fēng)險的生物標記物，能預(yù)測胃癌患者的預(yù)后情況,。（生物谷：Bioon.com）
doi:10.1371/journal.pone.0040037
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Identification of hsa-miR-335 as a Prognostic Signature in Gastric Cancer
Zhi Yan1, Yimin Xiong1, Weitian Xu1, Juan Gao1, Yi Cheng1, Zhigang Wang2, Fang Chen3, Guorong Zheng1*
Background
Gastric cancer (GC) is one of the most common malignancy and primary cause of death in Chinese cancer patients. Recurrence is a major factor leading to treatment failure and low level of 5-year survival rate in GC patients following surgical resection. Therefore, identification of biomarkers with potential in predicting recurrence risk is the key problem of the prognosis in GC patients.
Patients and Methods
A total of 74 GC patients were selected for systematic analysis, consisting of 31 patients with recurrence and 43 patients without recurrence. Firstly, miRNAs microarray and bioinformatics methods were used to characterize differential expressed miRNAs from primary tumor samples. Following, we used a ROC method to select signature with best sensitivity and specificity. Finally, we validated the signature in GC samples (frozen fresh and blood samples) using quantitative PCR.
Results
We have identified 12 differential miRNAs including 7 up-regulated and 5 down-regulated miRNAs in recurrence group. Using ROC method, we further ascertained hsa-miR-335 as a signature to recognize recurrence and non-recurrence cases in the training samples. Moreover, we validated this signature using quantitative PCR method in 64 test samples with consistent result with training set. A high frequency recurrence and poor survival were observed in GC cases with high level of hsa-miR-335 (P<0.001). In addition, we evaluated that hsa-miR-335 were involved in regulating target genes in several oncogenic signal-pathways, such as p53, MAPK, TGF-β, Wnt, ERbB, mTOR, Toll-like receptor and focal adhesion.
Conclusion
Our results indicate that the hsa-miR-335 has the potential to recognize the recurrence risk and relate to the prognosis of GC patients.
