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RAD51B as a potential biomarker for early detection and poor prognostic evaluation contributes to tumorigenesis of gastric cancer

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Tumor Biology

Abstract

Gastric cancer (GC) is a common and deadly disease worldwide. Outcomes of patients are poor largely due to chemoresistance or recurrence. Thus, identifying novel biomarkers to predict response to therapy and/or prognosis are urgently needed. RAD51B, a key player in DNA repair/recombination, has the potential to be a candidate oncogene and biomarker for cancer diagnosis and prognosis. However, its relationship with GC remains unclear. To evaluate clinicopathological and prognostic significance of RAD51B in GC, we examined messenger RNA (mRNA) and protein expression via quantitative real-time polymerase chain reaction (qRT-PCR) from 69 and tissue microarray from 144 GC patients, respectively. Our results showed that RAD51B mRNA expression was significantly up-regulated in tumors compared to that of matched noncancerous tissues (P < 0.001). In parallel, RAD51B protein showed a mainly nucleus-staining pattern, and the positive rate in tumors and stomach atypical hyperplasia was significantly higher than that in matched noncancerous tissues (P = 0.015). Moreover, high level of RAD51B protein was correlated with advanced stage (P = 0.009), aggressive differentiation (P = 0.022), and lymph node metastasis (P = 0.001). Further, Kaplan-Meier analysis indicated that patients with high level of RAD51B expression exhibited worse overall survival compared to patients with low level (P = 0.040). A multivariate Cox regression analysis suggested that RAD51B may be an independent prognostic factor for GC patients in Chinese population (P = 0.004). Additionally, functional studies indicated that over-expression of RAD51B promoted cell proliferation, aneuploidy, and drug resistance, while RAD51B knockdown led to G1 arrest and sensitized cells to 5-fluorouracil (5-FU). In conclusion, RAD51B may act as an oncogene during GC progression, and its hyper-expression may be a potential biomarker for early detection and poor prognosis of GC.

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Abbreviations

GC:

Gastric cancer

HR:

Homologous recombination

DSB:

DNA double-strand breaks

HER2:

Human epidermal growth factor receptor-2

EGFR:

Epidermal growth factor receptor

PI3K/Akt:

Phosphatidylinositol 3-kinase/Ak thymoma

5-FU:

5-Fluorouracil

TMA:

Tissue microarray

OS:

Overall survival

IHC:

Immunohistochemistry

qRT-PCR:

Quantitative real-time polymerase chain reaction

SCR:

Scrammed control siRNA

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (81330063), the Innovative Team in Science and Technology of Shanxi (2013131023), and the Program for the Outstanding Innovative Teams of Higher Learning Institutions of Shanxi to X.C. We thank Qimin Zhan (Peking University Cancer Hospital and Institute) for guidance of this study and for critical reading of this article. We thank Dr. Jinjuan Yao (Memorial Sloan Kettering Cancer, Weill Cornell Medical Center) for editing this article.

Author’s contributions

Y.K.C. performed the experiments and data analyses and wrote the manuscript. B.Y. performed the experiments and data analyses. X.C. and Y.F.X. provided the clinical samples and coordinated and performed the pathology reviews. X.C. conceived this study, designed the experiments, and commented to edit the manuscript. All of the authors discussed the results and implications and commented on the manuscript.

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Authors and Affiliations

  1. Beijing New Oriental Foreign Language School at Yangzhou, Yangzhou, Jiangsu, 225006, China

    Yikun Cheng

  2. Department of Tumor Surgery, Shanxi Cancer Hospital, Taiyuan, Shanxi, 030001, People’s Republic of China

    Bin Yang

  3. Department of Pathology, Shanxi Cancer Hospital, Taiyuan, Shanxi, 030001, People’s Republic of China

    Yanfeng Xi

  4. Department of Endoscopy, Shanxi Cancer Hospital, Taiyuan, Shanxi, 030001, China

    Xing Chen

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  1. Yikun Cheng
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  2. Bin Yang
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Correspondence to Yanfeng Xi or Xing Chen.

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Electronic supplementary material

Fig. S1

Representative image shows the immunohistochemical staining of RAD51B on TMA (GIF 102 kb)

High-resolution image (TIFF 2927 kb)

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Cheng, Y., Yang, B., Xi, Y. et al. RAD51B as a potential biomarker for early detection and poor prognostic evaluation contributes to tumorigenesis of gastric cancer. Tumor Biol. 37, 14969–14978 (2016). https://doi.org/10.1007/s13277-016-5340-3

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  • DOI: https://doi.org/10.1007/s13277-016-5340-3

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