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Erschienen in: Tumor Biology 11/2016

20.09.2016 | Original Article

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

verfasst von: Yikun Cheng, Bin Yang, Yanfeng Xi, Xing Chen

Erschienen in: Tumor Biology | Ausgabe 11/2016

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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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Literatur
1.
Zurück zum Zitat Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cance. 2015;136:E359–86.CrossRef Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cance. 2015;136:E359–86.CrossRef
2.
Zurück zum Zitat Koh JC, Loo WM, Goh KL, Sugano K, Chan WK, Chiu WY, et al. Asian consensus on the relationship between obesity and gastrointestinal and liver diseases. J Gastroenterol Hepatol. 2016. doi:10.1111/jgh.13385. Koh JC, Loo WM, Goh KL, Sugano K, Chan WK, Chiu WY, et al. Asian consensus on the relationship between obesity and gastrointestinal and liver diseases. J Gastroenterol Hepatol. 2016. doi:10.​1111/​jgh.​13385.
3.
Zurück zum Zitat Veisani Y, Delpisheh A. Survival rate of gastric cancer in Iran; a systematic review and meta-analysis. Gastroenterol Hepatol Bed Bench. 2016;9(2):78–86.PubMedPubMedCentral Veisani Y, Delpisheh A. Survival rate of gastric cancer in Iran; a systematic review and meta-analysis. Gastroenterol Hepatol Bed Bench. 2016;9(2):78–86.PubMedPubMedCentral
4.
Zurück zum Zitat Schulte N, Ebert MP, Härtel N. Gastric cancer: new drugs—new strategies. Gastrointest Tumors. 2014;1(4):180–94.CrossRefPubMed Schulte N, Ebert MP, Härtel N. Gastric cancer: new drugs—new strategies. Gastrointest Tumors. 2014;1(4):180–94.CrossRefPubMed
5.
Zurück zum Zitat Hayakawa Y, Sethi N, Sepulveda AR, Bass AJ, Wang TC. Oesophageal adenocarcinoma and gastric cancer: should we mind the gap? Nat Rev Cancer. 2016;16(5):305–18.CrossRefPubMed Hayakawa Y, Sethi N, Sepulveda AR, Bass AJ, Wang TC. Oesophageal adenocarcinoma and gastric cancer: should we mind the gap? Nat Rev Cancer. 2016;16(5):305–18.CrossRefPubMed
6.
Zurück zum Zitat Izuishi K, Mori H. Recent strategies for treating stage IV gastric cancer: roles of palliative gastrectomy, chemotherapy, and radiotherapy. J Gastrointestin Liver Dis. 2016;25(1):87–94.PubMed Izuishi K, Mori H. Recent strategies for treating stage IV gastric cancer: roles of palliative gastrectomy, chemotherapy, and radiotherapy. J Gastrointestin Liver Dis. 2016;25(1):87–94.PubMed
7.
Zurück zum Zitat Jia S, Cai J. Update on biomarkers in development of anti-angiogenic drugs in gastric cancer. Anticancer Res. 2016;36(3):1111–8.PubMed Jia S, Cai J. Update on biomarkers in development of anti-angiogenic drugs in gastric cancer. Anticancer Res. 2016;36(3):1111–8.PubMed
8.
Zurück zum Zitat Deng N, Goh LK, Wang H, Das K, Tao J, Tan IB, et al. Acomprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets. Gut. 2012;61:673–84.CrossRefPubMedPubMedCentral Deng N, Goh LK, Wang H, Das K, Tao J, Tan IB, et al. Acomprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets. Gut. 2012;61:673–84.CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Obermannová R, Lordick F. Insights into next developments in advanced gastric cancer. Curr Opin Oncol. 2016;28:367–75.CrossRefPubMed Obermannová R, Lordick F. Insights into next developments in advanced gastric cancer. Curr Opin Oncol. 2016;28:367–75.CrossRefPubMed
10.
Zurück zum Zitat Shah MA, Janjigian YY, Stoller R, Shibata S, Kemeny M, Krishnamurthi S, et al. Randomized multicenter phase II study of modified docetaxel, cisplatin, and fluorouracil (DCF) versus DCF plus growth factor supporting patients with metastatic gastric adenocarcinoma: a study of the US gastric cancer consortium. J ClinOnco. 2015;33:3874–9.CrossRef Shah MA, Janjigian YY, Stoller R, Shibata S, Kemeny M, Krishnamurthi S, et al. Randomized multicenter phase II study of modified docetaxel, cisplatin, and fluorouracil (DCF) versus DCF plus growth factor supporting patients with metastatic gastric adenocarcinoma: a study of the US gastric cancer consortium. J ClinOnco. 2015;33:3874–9.CrossRef
11.
Zurück zum Zitat Krumm A, Barckhausen C, Kücük P, Tomaszowski KH, Loquai C, Fahrer J, et al. Enhanced histone deacetylase activity in malignant melanoma provokes RAD51 and FANCD2 triggered drug resistance. Cancer Res. 2016;76:3067–77.CrossRefPubMed Krumm A, Barckhausen C, Kücük P, Tomaszowski KH, Loquai C, Fahrer J, et al. Enhanced histone deacetylase activity in malignant melanoma provokes RAD51 and FANCD2 triggered drug resistance. Cancer Res. 2016;76:3067–77.CrossRefPubMed
12.
Zurück zum Zitat Suwaki N, Klare K, Tarsounas M. RAD51 paralogs: roles in DNA damage signalling, recombinational repair and tumorigenesis. Semin Cell Dev Biol. 2011;22(8):898–905.CrossRefPubMed Suwaki N, Klare K, Tarsounas M. RAD51 paralogs: roles in DNA damage signalling, recombinational repair and tumorigenesis. Semin Cell Dev Biol. 2011;22(8):898–905.CrossRefPubMed
13.
Zurück zum Zitat Nagathihallia NS, Nagarajub G. RAD51 as a potential biomarker and therapeutic target for pancreatic cancer. Biochim Biophys Acta. 2011;1816:209–18. Nagathihallia NS, Nagarajub G. RAD51 as a potential biomarker and therapeutic target for pancreatic cancer. Biochim Biophys Acta. 2011;1816:209–18.
14.
Zurück zum Zitat Thacker J. The RAD51 gene family, genetic instability and cancer. Cancer Lett. 2005;219(2):125–35.CrossRefPubMed Thacker J. The RAD51 gene family, genetic instability and cancer. Cancer Lett. 2005;219(2):125–35.CrossRefPubMed
16.
Zurück zum Zitat Zwicker J, Brüsselbach S, Jooss KU, Sewing A, Behn M, Lucibello FC, Müller R. Functional domains in cyclin D1: pRb-kinase activity is not essential for transformation. Oncogene. 1999;18:19–25.CrossRefPubMed Zwicker J, Brüsselbach S, Jooss KU, Sewing A, Behn M, Lucibello FC, Müller R. Functional domains in cyclin D1: pRb-kinase activity is not essential for transformation. Oncogene. 1999;18:19–25.CrossRefPubMed
17.
Zurück zum Zitat Halaban R. Rb/E2F: a two-edged sword in the melanocytic system. Cancer Metastasis Rev. 2005;24:339–56.CrossRefPubMed Halaban R. Rb/E2F: a two-edged sword in the melanocytic system. Cancer Metastasis Rev. 2005;24:339–56.CrossRefPubMed
18.
Zurück zum Zitat Burlaka AP, Ganusevich II, Gafurov MR, Lukin SM, Sidorik EP. Stomach cancer: interconnection between the redox state, activity of MMP-2, MMP-9 and stage of tumor growth. Cancer Microenviron. 2016;9(1):27–32.CrossRefPubMedPubMedCentral Burlaka AP, Ganusevich II, Gafurov MR, Lukin SM, Sidorik EP. Stomach cancer: interconnection between the redox state, activity of MMP-2, MMP-9 and stage of tumor growth. Cancer Microenviron. 2016;9(1):27–32.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Tang S, Wu WK, Li X, Wong SH, Wong N, Chan MT, et al. Stratification of digestive cancers with different pathological features and survival outcomes by microRNA expression. Sci Rep. 2016;6:24466.CrossRefPubMedPubMedCentral Tang S, Wu WK, Li X, Wong SH, Wong N, Chan MT, et al. Stratification of digestive cancers with different pathological features and survival outcomes by microRNA expression. Sci Rep. 2016;6:24466.CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Smid D, Kulda V, Srbecka K, Kubackova D, Dolezal J, Daum O, et al. Tissue microRNAs as predictive markers for gastric cancer patients undergoing palliative chemotherapy. Int J Oncol. 2016. doi:10.3892/ijo.2016.3484.PubMed Smid D, Kulda V, Srbecka K, Kubackova D, Dolezal J, Daum O, et al. Tissue microRNAs as predictive markers for gastric cancer patients undergoing palliative chemotherapy. Int J Oncol. 2016. doi:10.​3892/​ijo.​2016.​3484.PubMed
21.
Zurück zum Zitat Chen KH, Yuan CT, Tseng LH, Shun CT, Yeh KH. Case report: mismatch repair proficiency and microsatellite stability in gastric cancer may not predict programmed death-1 blockade resistance. J Hematol Oncol. 2016;9:29.CrossRefPubMedPubMedCentral Chen KH, Yuan CT, Tseng LH, Shun CT, Yeh KH. Case report: mismatch repair proficiency and microsatellite stability in gastric cancer may not predict programmed death-1 blockade resistance. J Hematol Oncol. 2016;9:29.CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Yamamoto M, Kurokawa Y, Miyazaki Y, Makino T, Takahashi T, Yamasaki M, et al. Usefulness of preoperative plasma fibrinogen versus other prognostic markers for predicting gastric cancer recurrence. World J Surg. 2016;40:1904–9.CrossRefPubMed Yamamoto M, Kurokawa Y, Miyazaki Y, Makino T, Takahashi T, Yamasaki M, et al. Usefulness of preoperative plasma fibrinogen versus other prognostic markers for predicting gastric cancer recurrence. World J Surg. 2016;40:1904–9.CrossRefPubMed
23.
Zurück zum Zitat Greene ECDNA. Sequence alignment during homologous recombination. J Biol Chem. 2016;291:11572–80.CrossRefPubMed Greene ECDNA. Sequence alignment during homologous recombination. J Biol Chem. 2016;291:11572–80.CrossRefPubMed
24.
Zurück zum Zitat Slupianek A, Hoser G, Majsterek I, Bronisz A, Malecki M, Blasiak J, et al. Fusion tyrosine kinases induce drug resistance by stimulation of homology-dependent recombination repair, prolongation of G(2)/M phase, and protection from apoptosis. Mol Cell Biol. 2002;22:4189–201.CrossRefPubMedPubMedCentral Slupianek A, Hoser G, Majsterek I, Bronisz A, Malecki M, Blasiak J, et al. Fusion tyrosine kinases induce drug resistance by stimulation of homology-dependent recombination repair, prolongation of G(2)/M phase, and protection from apoptosis. Mol Cell Biol. 2002;22:4189–201.CrossRefPubMedPubMedCentral
Metadaten
Titel
RAD51B as a potential biomarker for early detection and poor prognostic evaluation contributes to tumorigenesis of gastric cancer
verfasst von
Yikun Cheng
Bin Yang
Yanfeng Xi
Xing Chen
Publikationsdatum
20.09.2016
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 11/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5340-3

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