PLoS One：胃癌预后标记物hsa-miR-335

胃癌（GC）是最常见的恶性肿瘤，在中国癌症患者中是引发死亡的首要原因之一。癌症复发的主要因素是治疗失败和胃癌患者手术切除后5年存活率水平低的主要原因。因此，筛选出能预测复发风险的潜在生物标志物是解决胃癌患者预后的关键问题。

近日，发表于PLoS One杂志上的一则研究证实hsa-miR-335可作为胃癌预后的标记物。研究人员纳入74例胃癌患者进行研究，包括31例复发和43例无复发胃癌患者。首先，原发肿瘤样本的miRNA芯片和生物信息学方法分析了miRNA的差异表达。之后，使用定量PCR验证出最适合恩的生物标记物。

结果确定了12个差异表达的miRNA，其中包括7歌上调的、5个下调的miRNA。进一步确定has-miR-335是最适合的复发预测因子。hsa-miR-335的高表达，胃癌复发率升高，生存期降低。此外，科研人员还评估了hsa-miR-335的几个致癌信号途径如P53、TGF-β，Wnt信号、ERBB、mTOR、Toll样受体等，这些都是与癌症转移密切相关的信号分子。

总之研究结果表明，hsa-miR-335是潜在的预测复发风险的生物标记物，能预测胃癌患者的预后情况。

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.