Evaluation of Micro-RNA Levels, Apoptosis and Oxidative Stress Markers in Patients Recieving Chemotherapy

Author(s): Idris Kirhan*, Fehmi Kas, Hüseyin Taskiran, Hakan Buyukhatipoglu, Ataman Gönel, Ismail Koyuncu

Journal Name: Combinatorial Chemistry & High Throughput Screening
Accelerated Technologies for Biotechnology, Bioassays, Medicinal Chemistry and Natural Products Research

Volume 23 , Issue 1 , 2020

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Abstract:

Objective: The primary objective of this study was to compare oxidative DNA damage markers, apoptosis markers and changes in miRNA levels in patients diagnosed with cancer and treated through chemotherapy. Our secondary objective was also to evaluate tumor responses that can be determined after post-chemotherapy clinical evaluations by physical examinations, laboratory results and radiological imagings, and to compare the clinical results to oxidative stress and apoptosis markers and micro RNA levels.

Materials and Methods: To do that we designed a prospective observational cross-sectional study. A total of 34 cancer patients and 27 healthy controls were included in the study from the Harran University School of Medicine Department of Oncology. Newly diagnosed chemotherapy or radiotherapy naive patients without any chronic diseases were included into the study. Patients with a poor performance status (ECOG 2 and 3) and patients who did not meet the inclusion criteria were excluded. The cancer patients received chemotherapy according to their scheduled periods. Blood samples were taken from the patients before the first chemotherapy course and before the second chemotherapy round. Patients were called for toxicity control on the 10th day after the chemotherapy. Pre-chemotherapy, post-chemotherapy and control group miR-29a expression levels, change in apoptosis markers and oxidative DNA damage markers were obtained and compared. We studied 8-hydroxy 2-deoxyguanosine, total oxidant status, total anti-oxidant status, and oxidative status index for oxidative stress markers. We studied M30 and M65 as apoptosis markers. Clinical results of efficiency of the chemotherapy was acquired and compared to biochemical markers based on chemotherapy results. Chemotherapy toxicities were recorded.

Results: As a result, we found oxidative DNA damage markers and apoptosis markers were high in the cancer group, demonstrating that oxidative DNA damage and apoptosis might play a direct or indirect role in cancer etiology. However, there were subtle differences between pre-chemotherapy and post-chemotherapy levels. Mir-29a expressions were lower in cancer patients as compared to controls. However, the expression levels were not significantly change in pre- and postchemotherapy status. Moreover, we found no relationship between clinical status of patients (progression and regression) and studied biochemical markers.

Conclusion: Thus, checking for DNA damage markers and taking precautions to lower the levels of these markers in individuals with cancer risk may be helpful in preventing cancer.

Keywords: Micro-RNA, miRNA, apoptosis, DNA damage, injury, damage, cancer, metastasis, prognosis, chemotherapy, miR-29a.

[1]
Van Leeuwen, F.F.; Travis, L.B. Second cancers. In: İçinde: De vita VT Jr Cancer Principle and Practice of Oncology, ; 7th ed; Hellman, S.; Rosenberg, SA., Eds., Philadelphia: WW Lippincott, . , 2005, Vol. 2 , pp. 575-602.
[2]
Manova, V.; Gecheff, K.; Stoilov, L. Efficient repair of bleomycin-induced double-strand breaks in barley ribosomal genes. Mutat. Res., 2006, 601(1-2), 179-190.
[http://dx.doi.org/10.1016/j.mrfmmm.2006.07.004] [PMID: 16930631]
[3]
Richardson, D.S.; Johnson, S.A. Anthracyclines in haematology: preclinical studies, toxicity and delivery systems. Blood Rev., 1997, 11(4), 201-223.
[http://dx.doi.org/10.1016/S0268-960X(97)90020-5] [PMID: 9481450]
[4]
Murray, R.K.; Mayes, P.A.; Granner, D.K.; Rodwell, V.W. Harper’s Biochemistry; McGraw Hill: New York, USA, 2000.
[5]
Ringer, D.P.; Schnipper, L.E. Principles of cancer Biology Lenhard. In: The American Cancer Society’s Clinical Oncology,; Lenhard R.E., Osteen R.T., Gansler T., Eds.; The American Cancer Society: Inc: Atlanta, USA,. , 2001, pp. 37-67.
[6]
Kuo, C.C.; Liu, J.F.; Shiah, H.S.; Ma, L.C.; Chang, J.Y. Tamoxifen accelerates proteasomal degradation of O6-methylguanine DNA methyltransferase in human cancer cells. Int. J. Cancer, 2007, 121(10), 2293-2300.
[http://dx.doi.org/10.1002/ijc.22927] [PMID: 17597106]
[7]
Shen, M.R.; Jones, I.M.; Mohrenweiser, H. Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans. Cancer Res., 1998, 58(4), 604-608.
[PMID: 9485007]
[8]
Ciccia, A.; Elledge, S.J. The DNA damage response: making it safe to play with knives. Mol. Cell, 2010, 40(2), 179-204.
[http://dx.doi.org/10.1016/j.molcel.2010.09.019] [PMID: 20965415]
[9]
Cheung-Ong, K.; Giaever, G.; Nislow, C. DNA-damaging agents in cancer chemotherapy: serendipity and chemical biology. Chem. Biol., 2013, 20(5), 648-659.
[http://dx.doi.org/10.1016/j.chembiol.2013.04.007] [PMID: 23706631]
[10]
Dreher, D.; Junod, A.F. Role of oxygen free radicals in cancer development. Eur. J. Cancer, 1996, 32A(1), 30-38.
[http://dx.doi.org/10.1016/0959-8049(95)00531-5] [PMID: 8695238]
[11]
Halliwell, B.; Gutteride, J.M.C. Oxidative stress: Adaptation, damage,repair and death. In: Free Radicals in Biology and Medicine, ; 3rd ed; Halliwell, B.; Gutteridge, J.M.C., Eds.; Oxford University Pres: Oxford, . , 1996, pp. 247-253.
[12]
Bartels, C.L.; Tsongalis, G.J. MicroRNAs: novel biomarkers for human cancer. Clin. Chem., 2009, 55(4), 623-631.
[http://dx.doi.org/10.1373/clinchem.2008.112805] [PMID: 19246618]
[13]
Cowland, J.B.; Hother, C.; Grønbaek, K. MicroRNAs and cancer. APMIS, 2007, 115(10), 1090-1106.
[http://dx.doi.org/10.1111/j.1600-0463.2007.apm_775.xml.x] [PMID: 18042145]
[14]
Calin, G.A.; Croce, C.M. MicroRNA signatures in human cancers. Nat. Rev. Cancer, 2006, 6(11), 857-866.
[http://dx.doi.org/10.1038/nrc1997] [PMID: 17060945]
[15]
Calin, G.A.; Croce, C.M. MicroRNA-cancer connection: the beginning of a new tale. Cancer Res., 2006, 66(15), 7390-7394.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-0800] [PMID: 16885332]
[16]
Cho, W.C. OncomiRs: the discovery and progress of microRNAs in cancers. Mol. Cancer, 2007, 6, 60.
[http://dx.doi.org/10.1186/1476-4598-6-60] [PMID: 17894887]
[17]
Zhang, B.; Pan, X.; Cobb, G.P.; Anderson, T.A. microRNAs as oncogenes and tumor suppressors. Dev. Biol., 2007, 302(1), 1-12.
[http://dx.doi.org/10.1016/j.ydbio.2006.08.028] [PMID: 16989803]
[18]
de Haas, E.C.; di Pietro, A.; Simpson, K.L.; Meijer, C.; Suurmeijer, A.J.; Lancashire, L.J.; Cummings, J.; de Jong, S.; de Vries, E.G.; Dive, C.; Gietema, J.A. Clinical evaluation of M30 and M65 ELISA cell death assays as circulating biomarkers in a drug-sensitive tumor, testicular cancer. Neoplasia, 2008, 10(10), 1041-1048.
[http://dx.doi.org/10.1593/neo.08620] [PMID: 18813353]
[19]
Kuo, T.Y.; Hsi, E.; Yang, I.P.; Tsai, P.C.; Wang, J.Y.; Juo, S.H. Computational analysis of mRNA expression profiles identifies microRNA-29a/c as predictor of colorectal cancer early recurrence. PLoS One, 2017, 7e31587
[http://dx.doi.org/10.1371/journal.pone.0031587] [PMID: 22348113]
[20]
Kamikawaji, K.; Seki, N.; Watanabe, M.; Mataki, H.; Kumamoto, T.; Takagi, K.; Mizuno, K.; Inoue, H. Regulation of LOXL2 and SERPINH1 by antitumor microRNA-29a in lung cancer with idiopathic pulmonary fibrosis. J. Hum. Genet., 2016, 61(12), 985-993.
[http://dx.doi.org/10.1038/jhg.2016.99] [PMID: 27488440]
[21]
Chen, L.; Xiao, H.; Wang, Z.H.; Huang, Y.; Liu, Z.P.; Ren, H.; Song, H. miR-29a suppresses growth and invasion of gastric cancer cells in vitro by targeting VEGF-A. BMB Rep., 2014, 47(1), 39-44.
[http://dx.doi.org/10.5483/BMBRep.2014.47.1.079] [PMID: 24209632]
[22]
Wu, Z.; Huang, X.; Huang, X.; Zou, Q.; Guo, Y. The inhibitory role of Mir-29 in growth of breast cancer cells. J. Exp. Clin. Cancer Res., 2013, 32, 98.
[http://dx.doi.org/10.1186/1756-9966-32-98] [PMID: 24289849]
[23]
Khamisipour, G.; Mansourabadi, E.; Naeimi, B.; Moazzeni, A.; Tahmasebi, R.; Hasanpour, M.; Mohammadi, M.M.; Mansourabadi, Z.; Shamsian, S. Knockdown of microRNA-29a regulates the expression of apoptosis-related genes in MCF-7 breast carcinoma cells. Mol. Clin. Oncol., 2018, 8(2), 362-369.
[PMID: 29435304]
[24]
Huang, Q.; Feng, J.; Wu, R.; Yang, Y.; Dai, C.; Li, J.; Liao, Y.; Xiang, M.; Wang, D.; Du, X.B. Total oxidant/antioxidant status in sera of patients with esophageal cancer. Med. Sci. Monit., 2017, 23, 3789-3794.
[http://dx.doi.org/10.12659/MSM.902210] [PMID: 28777781]
[25]
Wu, R.; Feng, J.; Yang, Y.; Dai, C.; Lu, A.; Li, J.; Liao, Y.; Xiang, M.; Huang, Q.; Wang, D.; Du, X.B. Significance of serum total oxidant/antioxidant status in patients with colorectal cancer. PLoS One, 2017, 12(1)e0170003
[http://dx.doi.org/10.1371/journal.pone.0170003] [PMID: 28103261]
[26]
Bukhari, S.A.; Zafar, K.; Rajoka, M.; İbrahim, Z.; Javed, S.; Sadiq, R. Oxidative stress-induced DNA damage and homocysteine accumulation may beinvolved in ovarian cancer progression in both young and old patients. Turk. J. Med. Sci., 2016, 46(3), 583-589.
[http://dx.doi.org/10.3906/sag-1406-17] [PMID: 27513230]
[27]
Dogan, R.; Meriç Hafiz, A.; Tugrul, S.; Ozturan, O.; Keskin, S.; Kocyigit, A. Can Oxidative Stress Parameters Be Used as Biomarkers for the Discrimination of Malignant Head and Neck Tumors. J. Craniofac. Surg., 2016, 27(3), e316-e320.
[http://dx.doi.org/10.1097/SCS.0000000000002575] [PMID: 27159871]
[28]
Singh, A.K.; Pandey, P.; Tewari, M.; Pandey, H.P.; Gambhir, I.S.; Shukla, H.S. Free radicals hasten head and neck cancer risk: A study of total oxidant, total antioxidant, DNA damage, and histological grade. J. Postgrad. Med., 2016, 62(2), 96-101.
[http://dx.doi.org/10.4103/0022-3859.180555] [PMID: 27089108]
[29]
Guo, C.; Li, X.; Wang, R.; Yu, J.; Ye, M.; Mao, L.; Zhang, S.; Zheng, S. Association between oxidative DNA damage and risk of colorectal cancer: sensitive determination of urinary 8-hydroxy-2′-deoxyguanosine by UPLC-MS/MS analysis. Sci. Rep., 2016, 6, 32581.
[http://dx.doi.org/10.1038/srep32581] [PMID: 27585556]
[30]
Płachetka, A.; Adamek, B.; Strzelczyk, J.K.; Krakowczyk, Ł.; Migula, P.; Nowak, P.; Wiczkowski, A. 8-hydroxy-2′-deoxyguanosine in colorectal adenocarcinoma--is it a result of oxidative stress? Med. Sci. Monit., 2013, 19, 690-695.
[http://dx.doi.org/10.12659/MSM.883999] [PMID: 23963109]
[31]
Malek-Hosseini, Z.; Khezri, A.; Amirghofran, Z. Circulating levels of M30 and M65 molecules in transitional cell carcinoma of the bladder and their relation to tumor progression. Iran. J. Cancer Prev., 2016, 9(2)e4086
[http://dx.doi.org/10.17795/ijcp-4086] [PMID: 27482329]
[32]
Smerage, J.B.; Budd, G.T.; Doyle, G.V.; Brown, M.; Paoletti, C.; Muniz, M.; Miller, M.C.; Repollet, M.I.; Chianese, D.A.; Connelly, M.C.; Terstappen, L.W.; Hayes, D.F. Monitoring apoptosis and Bcl-2 on circulating tumor cells in patients with metastatic breast cancer. Mol. Oncol., 2013, 7(3), 680-692.
[http://dx.doi.org/10.1016/j.molonc.2013.02.013] [PMID: 23538216]
[33]
Saigusa, S.; Inoue, Y.; Tanaka, K.; Okugawa, Y.; Toiyama, Y.; Uchida, K.; Mohri, Y.; Kusunoki, M. Lack of M30 expression correlates with factors reflecting tumor progression in rectal cancer with preoperative chemoradiotherapy. Mol. Clin. Oncol., 2014, 2(1), 99-104.
[http://dx.doi.org/10.3892/mco.2013.189] [PMID: 24649315]


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VOLUME: 23
ISSUE: 1
Year: 2020
Page: [17 - 27]
Pages: 11
DOI: 10.2174/1386207323666191224111348
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