Clinicopathological and Prognostic Characteristics of RAD51 in Colorectal Cancer
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients and Tissue Samples
2.2. RNA Isolation and mRNA Expression Analysis
2.3. The Cancer Genome Atlas (TCGA) Data Analysis
2.4. Statistical Analysis
3. Results
3.1. Patient and Tumor Characteristics
3.2. Survival Analyses According to the Prognostic Model
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Zhai, H.; Ju, J. Implications of microRNAs in colorectal cancer development, diagnosis, prognosis, and therapeutics. Front. Genet. 2011, 2, 78. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Agostini, M.; Pucciarelli, S.; Calore, F.; Bedin, C.; Enzo, M.; Nitti, D. miRNAs in colon and rectal cancer: A consensus for their true clinical value. Clin. Chim. Acta 2010, 411, 1181–1186. [Google Scholar] [CrossRef] [PubMed]
- Zhou, Q.; Li, K.; Lin, G.Z.; Shen, J.C.; Dong, H.; Gu, Y.T.; Liu, H.Z. Incidence trends and age distribution of colorectal cancer by subsite in Guangzhou, 2000–2011. Chin. J. Cancer 2015, 34, 34. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liao, Y.; Li, S.; Chen, C.; He, X.; Lin, F.; Wang, J.; Yang, Z.; Lan, P. Screening for colorectal cancer in Tianhe, Guangzhou: Results of combining fecal immunochemical tests and risk factors for selecting patients requiring colonoscopy. Gastroenterol. Rep. 2017, 6, 132–136. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, J.N.; Zhao, L.; Zheng, W.Y.; Miao, Z.; Tang, X.Y.; Qian, J.M. The trends in clinical characteristics of colon cancer in last two decades. Zhonghua Nei Ke Za Zhi 2010, 49, 226–229. [Google Scholar]
- Ju, J.; Chang, S.; Wang, H.; Yang, S.; Jiang, J.; Chen, W.; Lin, T.; Hsu, H.; Wang, F.; Lin, J. Changes in disease pattern and treatment outcome of colorectal cancer: A review of 5,474 cases in 20 years. Int. J. Colorectal Dis. 2007, 22, 855–862. [Google Scholar] [CrossRef]
- Tennstedt, P.; Fresow, R.; Simon, R.; Marx, A.; Terracciano, L.; Petersen, C.; Borgmann, K.; Sauter, G.; Dikomey, E. RAD51 overexpression is a negative prognostic marker for colorectal adenocarcinoma. Int. J. Cancer 2013, 132, 2118–2126. [Google Scholar] [CrossRef]
- Javle, M.; Curtin, N.J. The role of PARP in DNA repair and its therapeutic exploitation. Br. J. Cancer 2011, 105, 1114–1122. [Google Scholar] [CrossRef] [Green Version]
- Benson, F.E.; Baumann, P.; West, S.C. Synergistic actions of Rad51 and Rad52 in recombination and DNA repair. Nature 1998, 391, 401–404. [Google Scholar] [CrossRef]
- West, S.C. Molecular views of recombination proteins and their control. Nat. Rev. Mol. Cell Biol. 2003, 4, 435–445. [Google Scholar] [CrossRef]
- Vispe, S.; Cazaux, C.; Lesca, C.; Defais, M. Overexpression of Rad51 protein stimulates homologous recombination and increases resistance of mammalian cells to ionizing radiation. Nucleic Acids Res. 1998, 26, 2859–2864. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Slupianek, A.; Hoser, G.; Majsterek, I.; Bronisz, A.; Malecki, M.; Blasiak, J.; Skorski, T.; Fishel, R. 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, 4189–4201. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hansen, L.T.; Lundin, C.; Spang-Thomsen, M.; Petersen, L.N.; Helleday, T. The role of RAD51 in etoposide (VP16) resistance in small cell lung cancer. Int. J. Cancer 2003, 105, 472–479. [Google Scholar] [CrossRef] [PubMed]
- Qiao, G.B.; Wu, Y.L.; Yang, X.N.; Zhong, W.Z.; Xie, D.; Guan, X.Y.; Stuerzbecher, H.W.; Fischer, D.; Kolberg, H.C.; Kruger, S. High-level expression of Rad51 is an independent prognostic marker of survival in non-small-cell lung cancer patients. Br. J. Cancer 2005, 93, 137–143. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shinohara, A.; Ogawa, H.; Matsuda, Y.; Ushio, N.; Ikeo, K.; Ogawa, T. Cloning of human, mouse and fission yeast recombination genes homologous to RAD51 and recA. Nat. Genet. 1993, 4, 239. [Google Scholar] [CrossRef]
- RESNICK, M.A. Investigating the genetic control of biochemical events in meiotic recombination. In Meiosis; Academic Press: New York, NY, USA, 1987; pp. 157–210. [Google Scholar]
- Shinohara, A.; Ogawa, H.; Ogawa, T. Rad51 protein involved in repair and recombination in S. cerevisiae is a RecA-like protein. Cell 1992, 69, 457–470. [Google Scholar] [CrossRef]
- Benson, F.E.; Stasiak, A.; West, S.C. Purification and characterization of the human Rad51 protein, an analogue of E. coli RecA. EMBO J. 1994, 13, 5764–5771. [Google Scholar] [CrossRef]
- Baumann, P.; Benson, F.E.; West, S.C. Human Rad51 protein promotes ATP-dependent homologous pairing and strand transfer reactions in vitro. Cell 1996, 87, 757–766. [Google Scholar] [CrossRef] [Green Version]
- Gupta, R.C.; Bazemore, L.R.; Golub, E.I.; Radding, C.M. Activities of human recombination protein Rad51. Proc. Natl. Acad. Sci. USA 1997, 94, 463–468. [Google Scholar] [CrossRef] [Green Version]
- Kato, M.; Yano, K.; Matsuo, F.; Saito, H.; Katagiri, T.; Kurumizaka, H.; Nagawa, H.; Miki, Y.; Nagawa, H.; Kasumi, F.; et al. Identification of Rad51 alteration in patients with bilateral breast cancer. J. Hum. Genet. 2000, 45, 133. [Google Scholar] [CrossRef] [Green Version]
- Tachon, G.; Cortes, U.; Guichet, P.O.; Rivet, P.; Balbous, A.; Masliantsev, K.; Karayan-Tapon, L.; Berger, A.; Boissonnade, O.; Wager, M. Cell Cycle Changes after Glioblastoma Stem Cell Irradiation: The Major Role of RAD51. Int. J. Mol. Sci. 2018, 19, 3018. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Welsh, J.W.; Ellsworth, R.K.; Kumar, R.; Fjerstad, K.; Martinez, J.; Nagel, R.B.; Stea, B.; Eschbacher, J. Rad51 protein expression and survival in patients with glioblastoma multiforme. Int. J. Radiat. Oncol. Biol. Phys. 2009, 74, 1251–1255. [Google Scholar] [CrossRef] [PubMed]
- Popova, M.; Henry, S.; Fleury, F. Posttranslational modifications of Rad51 protein and its direct partners: Role and effect on homologous recombination–mediated DNA repair. DNA Repair 2011, 1, 143–160. [Google Scholar]
- Daboussi, F.; Dumay, A.; Delacôte, F.; Lopez, B.S. DNA double-strand break repair signalling: The case of RAD51 post-translational regulation. Cell. Signal. 2002, 14, 969–975. [Google Scholar] [CrossRef]
- PLoS ONE Editors. Retraction: Overexpression of Rad51 Predicts Poor Prognosis in Colorectal Cancer: Our Experience with 54 Patients. PLoS ONE 2018, 13, e0206398. [Google Scholar] [CrossRef]
- Han, H.; Bearss, D.J.; Browne, L.W.; Calaluce, R.; Nagle, R.B.; Von Hoff, D.D. Identification of differentially expressed genes in pancreatic cancer cells using cDNA microarray. Cancer Res. 2002, 62, 2890–2896. [Google Scholar]
- Maacke, H.; Jost, K.; Opitz, S.; Miska, S.; Yuan, Y.; Hasselbach, L.; Stürzbecher, H.W.; Lüttges, J.; Kalthoff, H. DNA repair and recombination factor Rad51 is over-expressed in human pancreatic adenocarcinoma. Oncogene 2000, 19, 2791. [Google Scholar] [CrossRef]
- Raderschall, E.; Bazarov, A.; Cao, J.; Lurz, R.; Smith, A.; Mann, W.; Haaf, T.; Ropers, H.; Sedivy, J.; Golub, E.; et al. Formation of higher-order nuclear Rad51 structures is functionally linked to p21 expression and protection from DNA damage-induced apoptosis. J. Cell Sci. 2002, 115, 153–164. [Google Scholar]
- Li, Y.; Yu, H.; Luo, R.; Zhang, Y.; Zhang, M.; Wang, X.; Jia, W.H. Elevated expression of Rad51 is correlated with decreased survival in resectable esophageal squamous cell carcinoma. J. Surg. Oncol. 2011, 104, 617–622. [Google Scholar] [CrossRef]
- Soderlund, K.; Skoog, L.; Fornander, T.; Askmalm, M.S. The BRCA1/BRCA2/Rad51 complex is a prognostic and predictive factor in early breast cancer. Radiother. Oncol. 2007, 84, 242–251. [Google Scholar] [CrossRef]
RAD51 Expression | p | ||
---|---|---|---|
(−) | (+) | ||
Total | 39 (81.2) | 9 (18.8) | |
Age | 0.741 | ||
≤60 | 15 (78.9) | 4 (21.1) | |
>60 | 24 (82.8) | 5 (17.2) | |
BMI | 0.517 | ||
≤25 | 26 (78.8) | 7 (21.2) | |
>25 | 13 (86.7) | 2 (13.3) | |
T stage | 0.027 | ||
T 1 | 0 (0.0) | 2 (100.0) | |
T 2 | 5 (83.3) | 1 (16.7) | |
T 3 | 26 (83.9) | 5 (16.1) | |
T 4 | 8 (88.9) | 1(11.1) | |
N stage | 0.957 | ||
N 0 | 23 (82.1) | 5 (17.9) | |
N 1 | 9 (81.8) | 2 (18.2) | |
N 2 | 7 (77.8) | 2 (22.2) | |
CEA (ng/mL) | 0.716 | ||
≤5 | 28 (80.0) | 7 (20.0) | |
>5 | 11 (84.6) | 2 (15.4) | |
Differentiation | 0.111 | ||
Well-differentiated | 1 (50.0) | 1 (50.0) | |
Moderately differentiated | 36 (85.7) | 6 (14.3) | |
Poorly differentiated | 2 (50.0) | 2 (50.0) | |
Lymphovascular invasion | 0.348 | ||
(−) | 15 (75.0) | 5 (25.0) | |
(+) | 24 (85.7) | 4 (14.3) | |
Perineural invasion | 0.091 | ||
(−) | 23 (74.2) | 8 (25.8) | |
(+) | 16 (94.1) | 1 (5.9) |
Age | BMI | CEA | RAD51 | ||
---|---|---|---|---|---|
Age | R | 1 | 0.032 | 0.212 | 0.165 |
P | 0.811 | 0.103 | 0.262 | ||
BMI | R | 0.032 | 1 | 0.087 | −0.046 |
P | 0.811 | 0.510 | 0.756 | ||
CEA | R | 0.212 | 0.087 | 1 | 0.041 |
P | 0.103 | 0.510 | 0.779 | ||
RAD51 | R | 0.165 | −0.046 | 0.041 | 1 |
P | 0.262 | 0.756 | 0.779 |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Lee, J.-H.; Bae, A.-N.; Jung, S.-J. Clinicopathological and Prognostic Characteristics of RAD51 in Colorectal Cancer. Medicina 2020, 56, 48. https://doi.org/10.3390/medicina56020048
Lee J-H, Bae A-N, Jung S-J. Clinicopathological and Prognostic Characteristics of RAD51 in Colorectal Cancer. Medicina. 2020; 56(2):48. https://doi.org/10.3390/medicina56020048
Chicago/Turabian StyleLee, Jae-Ho, An-Na Bae, and Soo-Jung Jung. 2020. "Clinicopathological and Prognostic Characteristics of RAD51 in Colorectal Cancer" Medicina 56, no. 2: 48. https://doi.org/10.3390/medicina56020048