Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Tumor Biology
Published in: Tumor Biology 6/2014

01-06-2014 | Research Article

Deregulation of base excision repair gene expression and enhanced proliferation in head and neck squamous cell carcinoma

Authors: Ishrat Mahjabeen, Kashif Ali, Xiaofeng Zhou, Mahmood Akhtar Kayani

Published in: Tumor Biology | Issue 6/2014

Login to get access

Abstract

Defects in the DNA damage repair pathway contribute to cancer. The major pathway for oxidative DNA damage repair is base excision repair (BER). Although BER pathway genes (OGG1, APEX1 and XRCC1) have been investigated in a number of cancers, our knowledge on the prognostic significance of these genes and their role in head and neck squamous cell carcinoma is limited. Protein levels of OGG1, APEX1 and XRCC1 and a proliferation marker, Ki-67, were examined by immunohistochemical analysis, in a cohort of 50 HNSCC patients. Significant downregulation of OGG1 (p < 0.04) and XRCC1 (p < 0.05) was observed in poorly differentiated HNSCC compared to mod–well-differentiated cases. Significant upregulation of APEX1 (p < 0.05) and Ki-67 (p < 0.05) was observed in poorly differentiated HNSCC compared to mod-well-differentiated cases. Significant correlation was observed between XRCC1 and OGG1 (r = 0.33, p < 0.02). Inverse correlations were observed between OGG1 and Ki-67 (r = −0.377, p < 0.005), between APEX1 and XRCC1 (r = −0.435, p < 0.002) and between OGG1 and APEX1 (r = −0.34, p < 0.02) in HNSCC. To confirm our observations, we examined BER pathway genes and a proliferation marker, Ki-67, expression at the mRNA level on 50 head and neck squamous cell carcinoma (HNSCC) and 50 normal control samples by quantitative real-time polymerase chain reaction. Significant downregulation was observed in case of OGG1 (p < 0.04) and XRCC1 (p < 0.02), while significant upregulation was observed in case of APEX1 (p < 0.01) and Ki-67 (p < 0.03) in HNSCC tissue samples compared to controls. Our data suggested that deregulation of base excision repair pathway genes, such as OGG1, APEX1 and XRCC1, combined with overexpression of Ki-67, a marker for excessive proliferation, may contribute to progression of HNSCC in Pakistani population.
Literature
1.
Spitz M, Wei Q, Dong Q, Amos CI, Wu X. Genetic susceptibility to lung cancer: the role of DNA damage and repair. Cancer Epidemiol Biomarkers Prev. 2003;12:689–98.PubMed
2.
Tudek B. Base excision repair modulation as a risk factor for human cancers. Mol Asp Med. 2007;28:258–75.CrossRef
3.
Mitra S, Izumi T, Boldogh I, Bhakat KK, Hill JW, Hazra TK. Choreography of oxidative damage repair in mammalian genomes. Free Radic Biol Med. 2002;33:15–28.CrossRefPubMed
4.
Kohno T, Shinmura K, Tosaka M, Tani M, Kim SR, Sugimura H, et al. Genetic polymorphisms and altered splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA. Oncogene. 1998;16:3219–25.CrossRefPubMed
5.
Campalans A, Marsin S, Nakabeppu Y, O'connor TR, Boiteux S, Radicella JP. XRCC1 interactions with multiple DNA glycosylases: a model for its recruitment to base excision repair. DNA Repair. 2005;4:826–35.CrossRefPubMed
6.
Fan CY, Liu KL, Huang HY, Barnes EL, Swalsky PA, Bakker A, et al. XRCC1 co-localizes and physically interacts with PCNA. Nucleic Acids Res. 2004;32:2193–201.PubMedCentralCrossRefPubMed
7.
Kumar A, Pant MC, Singh SH, Khandelwal S. Reduced expression of DNA repair genes (XRCC1, XPD, and OGG1) in squamous cell carcinoma of head and neck in North India. Tumor Biol. 2012;33(1):111–9.CrossRef
8.
Fortini P, Pascucci B, Parlanti E, D’Errico M, Simonelli V, Dogliotti E. The base excision repair: mechanisms and its relevance for cancer susceptibility. Biochimie. 2003;85:1053–71.CrossRefPubMed
9.
10.
Vidal AE, Boiteux S, Hickson ID, Radicella JP. XRCC1 coordinates the initial and late stages of DNA abasic site repair through protein–protein interactions. EMBO J. 2001;20:6530–9.PubMedCentralCrossRefPubMed
11.
Sossou M, Flohr-Beckhaus C, Schulz I, Daboussi F, Epe B, Radicella JP. APE1 overexpression in XRCC1-deficient cells complements the defective repair of oxidative single strand breaks but increases genomic instability. Nucleic Acids Res. 2005;33(1):298–306.PubMedCentralCrossRefPubMed
12.
Ashraf MJ, Maghbul M, Azarpira N, Khademi B. Expression of Ki67 and P53 in primary squamous cell carcinoma of the larynx. Indian J Pathol Microbiol. 2010;53:661–5.CrossRefPubMed
13.
Tang QL, Fan S, Li HG, Chen WL, Shen XM, Yuan XP, et al. Expression of Cyr61 in primary salivary adenoid cystic carcinoma and its relation to Ki-67 and prognosis. Oral Oncol. 2011;47:365–70.CrossRefPubMed
14.
Okabe M, Inagaki H, Murase T, Inoue M, Nagai N, Eimoto T. Prognostic significance of p27 and Ki-67 expression in mucoepidermoid carcinoma of the intraoral minor salivary gland. Mod Pathol. 2001;14:1008–14.CrossRefPubMed
15.
Schmilovitz-Weiss H, Tobar A, Halpern M, Levy I, Shabtai E, Ben-Ari Z. Tissue expression of squamous cellular carcinoma antigen and Ki67 in hepatocellular carcinoma-correlation with prognosis: a historical prospective study. Diagn Pathol. 2011;6:121.PubMedCentralCrossRefPubMed
16.
Faratian D, Munro A, Twelves C, Bartlett JM. Membranous and cytoplasmic staining of Ki67 is associated with HER2 and ER status in invasive breast carcinoma. Histopathology. 2009;54:254–7.CrossRefPubMed
17.
Han B, Lin S, Yu LJ, Wang RZ, Wang YY. Correlation of 18 F-FDG PET activity with expressions of survivin, Ki67, and CD34 in non-small-cell lung cancer. Nucl Med Commun. 2009;30:831–7.CrossRefPubMed
18.
Fischer CA, Jung M, Zlobec I, Green E, Storck C, Tornillo L, et al. Co-overexpression of p21 and Ki-67 in head and neck squamous cell carcinoma relative to a significantly poor prognosis. Head Neck. 2011;33:267–73.CrossRefPubMed
19.
Mahjabeen I, Baig RM, Masood N, Sabir M, Malik FA, Kayani MA. OGG1 Gene sequence variation in head and neck cancer patients in Pakistan. Asian Pac J Cancer Prev. 2011;12:2779–83.PubMed
20.
Mahjabeen I, Baig RM, Masood N, Sabir M, Inayat U, Malik FA, et al. Novel mutations of OGG1 base excision repair pathway gene in laryngeal cancer patients. Fam Cancer. 2012;11(4):587–93.CrossRefPubMed
21.
Mahjabeen I, Baig RM, Sabir M, Kayani MA. Genetic and expressional variations of APEX1 are associated with increased risk of head and neck cancer. Mutagenesis. 2013;28(2):213–8.CrossRefPubMed
22.
Mahjabeen I, Baig RM, Masood N, Sabir M, Inayat U, Malik FA, et al. Genetic variations in XRCC1 gene in sporadic head and neck cancer (HNC) patients. Pathol Oncol Res. 2012;19(20):183–8.PubMed
23.
Mahjabeen I, Chen Z, Zhou X, Kayani MA. Decreased mRNA expression levels of base excision repair (BER) pathway genes is associated with enhanced Ki-67 expression in HNSCC. Med Oncol. 2012;29(5):3620–5.CrossRefPubMed
24.
Wang YX, Sun YE, Li XH, Wang ZB, Tong XY, Liu YL. Comparative study on molecular staging of lymph nodes in non-small cell lung cancer patients. Ai Zheng. 2009;28(3):318–22.PubMed
25.
Al-Moundhri MS, Nirmala V, Al-Hadabi I, Al-Mawaly K, Burney I, Al-Nabhani M, et al. The prognostic significance of p53, p27 kip1, p21 waf1, HER-2/neu, and Ki67 proteins expression in gastric cancer: a clinicopathological and immunohistochemical study of 121 Arab patients. J Surg Oncol. 2005;91(4):243–52.CrossRefPubMed
26.
Mambo E, Chatterjee A, Souza-Pinto NC, Mayard S, Hogue BA, Hoque M, et al. Oxidized guanine lesions and hOgg1 activity in lung cancer. Oncogene. 2005;24:4496–508.CrossRefPubMed
27.
Kunisada M, Sakumi K, Tominaga Y, Budiyanto A, Ueda M, Ichihashi M, et al. 8-Oxoguanine formation induced by chronic UVB exposure makes Ogg1 knockout mice susceptible to skin carcinogenesis. Cancer Res. 2005;65:6006–10.CrossRefPubMed
28.
Huang XX, Scolyer RA, Abubakar A, Halliday GM. Human 8-oxoguanine-DNA glycosylase-1 is downregulated in human basal cell carcinoma. Mol Genet Metab. 2012;106:127–30.CrossRefPubMed
29.
Karihtala P, Kauppila S, Puistola U, Jukkola-Vuorinen A. Absence of the DNA repair enzyme human 8-oxoguanine glycosylase is associated with an aggressive breast cancer phenotype. Br J Cancer. 2012;106:344–7.PubMedCentralCrossRefPubMed
30.
Salim EI, Morimura K, Menesi A, El-Lity M, Fukushima S, Wanibuchi H. Elevated oxidative stress and DNA damage and repair levels in urinary bladder carcinomas associated with schistosomiasis. Int J Cancer. 2008;123:601–8.CrossRefPubMed
31.
Ku YP, Jin M, Kim KH, Ahn YJ, Yoon SP, You HJ, et al. Immunolocalization of 8-OHdG and OGG1 in pancreatic islets of streptozotocin-induced diabetic rats. Acta Histochem. 2009;111:138–44.CrossRefPubMed
32.
Preston TJ, Henderson JT, McCallum GP, Wells PG. Base excision repair of reactive oxygen species-initiated 7, 8- dihydro-8-oxo-2′-deoxyguanosine inhibits the cytotoxicity of platinum anticancer drugs. Mol Cancer Ther. 2009;8(7):2015–26.PubMedCentralCrossRefPubMed
33.
Moore DH, Michael H, Tritt R, Parsons SH, Kelley MR. Alternations in the expression of the DNA repair/ redox enzyme APE/ref-1 in epithelial ovarian cancers. Clin Cancer Res. 2000;6:602–9.PubMed
34.
Kelley MR, Cheng L, Foster R, Tritt R, Jiang J, Broshears J, et al. Elevated and altered expression of the multifunctional DNA base excision repair and redox enzyme Ape1/ref-1 in prostate cancer. Clin Cancer Res. 2001;7:824–30.PubMed
35.
Bobola MS, Finn LS, Ellenbogen RG, Geyer JR, Berger MS, Braga JM, et al. Apurinic/apyrimidinic endonuclease activity is associatedwith response to radiation and chemotherapy in medulloblastoma and primitive neuroectodermal tumors. Clin Cancer Res. 2005;11(20):7405–14.CrossRefPubMed
36.
Yang S, Irani K, Heffron SE, Jurnak F, Meyskens FLJ. Alterations in the expression of the apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/ref-1) in human melanoma and identification of the therapeutic potential of resveratrol as an APE/ref-1 inhibitor. Mol Cancer Ther. 2005;4(12):1923–35.CrossRefPubMed
37.
Raffoul JJ, Banerjee S, Singh-Gupta V, Knoll ZV, Fite A, Zhang H, et al. Down-regulation of apurinic/apyrimidinic endonuclease 1/redox factor-1 expression by soy isoflavones enhances prostate cancer radiotherapy in vitro and in vivo. Cancer Res. 2007;67(5):2141–9.CrossRefPubMed
38.
Jiang L, Liu X, Chen Z, Jin Y, Heidbreder CE, Kolokythas A, et al. MicroRNA-7 targets insulin-like growth factor 1 receptor (IGF1R) in tongue squamous cell carcinoma cells. Biochem J. 2010;432:199–205.PubMedCentralCrossRefPubMed
39.
Fishel ML, Jiang Y, Rajeshkumar NV, Scandura G, Sinn AL, He Y, et al. Impact of APE1/ref-1 redox inhibition on pancreatic tumor growth. Mol Cancer Ther. 2011;10(9):1698–708.PubMedCentralCrossRefPubMed
40.
Schindl M, Oberhuber G, Pichlbauer EG, Obermair A, Birner P, Kelley MR. DNA repair-redox enzyme apurinic endonuclease in cervical cancer: evaluation of redox control of HIF-1α and prognostic significance. Int J Oncol. 2001;19:799–802.PubMed
41.
Freitas S, Moore DH, Michael H, Kelley MR. Studies of apurinic/apyrimidinic endonuclease/ref-1 expression in epithelial ovarian cancer: correlations with tumor progression and platinum resistance. Clin Cancer Res. 2003;9:4689–94.PubMed
42.
Lee JW, Jin J, Rha KS, Kim YM. Expression pattern of apurinic/apyrimidinic endonuclease in sinonasal squamous cell carcinoma. Otolaryngol Head Neck Surg. 2012;147(4):788–95.CrossRefPubMed
43.
Ford BN, Ruttan CC, Kyle VL, Brackley ME, Glickman BW. Identification of single nucleotide polymorphisms in human DNA repair genes. Carcinogenesis. 2000;21:1977–81.CrossRefPubMed
44.
Hu JJ, Smith TR, Miller MS, Mohrenweiser HW, Golden A, Case LD. Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity. Carcinogenesis. 2001;22:917–22.CrossRefPubMed
45.
Liu W, AO L, Cui Z, Zhou Z, Zhou Y, Yuan X, et al. Molecular analysis of DNA repair gene methylation and protein expression during chemical-induced rat lung carcinogenesis. Biochem Biophys Res Commun. 2011;408:595–601.CrossRefPubMed
46.
Wang P, Tang JT, Peng YS, Chen XY, Zhang YJ, Fang JY. XRCC1 downregulated through promoter hypermethylation is involved in human gastric carcinogenesis. J Dig Dis. 2010;11:343–51.CrossRefPubMed
47.
Wang S, Wu X, Chen Y, Zhang J, Ding J, Zhou Y, et al. Prognostic and predictive role of JWA and XRCC1 expressions in gastric cancer. Clin Cancer Res. 2012;18(10):2987–96.CrossRefPubMed
48.
Chetty C, Dontula R, Gujrati M, Dinh DH, Lakka SS. Blockade of SOX4 mediated DNA repair by SPARC enhances radioresponse in medulloblastoma. Cancer Lett. 2012;323:188–98.PubMedCentralCrossRefPubMed
49.
Sak SC, Harnden P, Johnston CF, Paul AB, Kiltie AE. APE1 and XRCC1 protein expression levels predict cancer-specific survival following radical radiotherapy in bladder cancer. Clin Cancer Res. 2005;11:6205.CrossRefPubMed
50.
Cheng X, Lu W, Ye F, Wan X, Xie X. The association of XRCC1 gene single nucleotide polymorphisms with response to neoadjuvant chemotherapy in locally advancedcervical carcinoma. J Exp Clin Cancer Res. 2009;28:91.PubMedCentralCrossRefPubMed
51.
Kang CH, Jang BG, Kim DW, Chung DH, Kim YT, Jheon S, et al. The prognostic significance of ERCC1, BRCA1, XRCC1, and betaIII-tubulin expression in patients with non-small cell lung cancer treated by platinum- and taxane-based neoadjuvant chemotherapy and surgical resection. Lung Cancer. 2010;68:478–83.CrossRefPubMed
52.
Ang MK, Patel MR, Yin XY, Sundaram S, Fritchie K, Zhao N, et al. High XRCC1 protein expression is associated with poorer survival in patients with head and neck squamous cell carcinoma. Clin Cancer Res. 2011;17(20):6542–52.PubMedCentralCrossRefPubMed
53.
Rybarova S, Vecanova J, Hodorova I, Mihalik J, Cizmarikova M, Mojzis J, et al. Association between polymorphisms of XRCC1, p53 and MDR1 genes, the expression of their protein products and prognostic significance in human breast cancer. Med Sci Monit. 2011;17:BR354–63.PubMedCentralCrossRefPubMed
54.
Fujimura M, Morita-Fujimura Y, Noshita N, Yoshimoto T, Chan PH. Reduction of the DNA base excision repair protein, XRCC1, may contribute to DNA fragmentation after cold injury-induced brain trauma in mice. Brain Res. 2000;869:105–11.CrossRefPubMed
55.
Rodrigues RB, Motta Rda R, Machado SM, Cambruzzi E, Zettler EW, Zettler CG, et al. Prognostic value of the immunohistochemistry correlation of Ki-67 and p53 in squamous cell carcinomas of the larynx. Braz J Otorhinolaryngol. 2008;74:855–9.PubMed
56.
Kim SJ, Shin HJ, Jung K, Baek S, Shin BK, Choi J, et al. Prognostic value of carbonic anhydrase IX and Ki-67 expression in squamous cell carcinoma of the tongue. Jpn J Clin Oncol. 2007;37:812–9.CrossRefPubMed
57.
Szczuraszek K, Mazur G, Jelen M, Dziegiel P, Surowiak P, Zabel M. Prognostic significance of Ki-67 antigen expression in non-Hodgkin’s lymphomas. Anticancer Res. 2008;28:1113–8.PubMed
58.
Cheang MCU, Chia SK, Voduc D, Gao D, Leung S, Snider J, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. JNCI. 2009;101(10):736–50.PubMedCentralCrossRefPubMed
59.
Sym S, Hong J, Cho E, Lee W, Chung M, Ha S, Park Y, Park J, Lee J, Shin D (2011) Prognostic impact of immunohistochemical expression of Ki-67 in patients with advanced gastric cancer who underwent curative Resection. J Clin Oncol 29
60.
61.
62.
Jiang Y, Zhou S, Sandusky GE, Kelley MR, Fishel ML. Reduced expression of DNA repair and redox signaling protein APE1/ref-1 impairs human pancreatic cancer cell survival, proliferation, and cell cycle progression. Cancer Investig. 2010;228:885–95.CrossRef
63.
Al-Attar A, Gossage L, Fareed KR, Shehata M, Mohammed M, Zaitoun AM, et al. Human apurinic/apyrimidinic endonuclease (APE1) is a prognostic factor in ovarian, gastro-oesophageal and pancreatico-biliary cancers. Br J Cancer. 2010;102:704–9.PubMedCentralCrossRefPubMed
64.
Grosch S, Kaina B. Transcriptional activation of apurinic/apyrimidinic endonuclease (Ape, ref-1) by oxidative stress requires CREB. Biochem Biophys Res Commun. 1999;261:859–63.CrossRefPubMed
65.
Vaezi A, Feldman CH, Niedernhofer LJ. ERCC1 and XRCC1 as biomarkers for lung and head and neck cancer. Pharmgenomics Pers Med. 2011;4:47–63.PubMedCentralPubMed
66.
Krskova L, Kalinova M, Brızova H, Mrhalova M, Sumerauer D, Kodet R. Molecular and immunohistochemical analyses of BCL2, KI-67, and cyclin D1 expression in synovial sarcoma. Cancer Genet Cytogenet. 2009;193:1–8.CrossRefPubMed
67.
Brouwer-Visser J, Cossio MJ, Chao SK, Huang GS. Effect of IGF2 overexpression on the tumorigenicity of human ovarian carcinoma cells. Cancer Res. 2012;72:1.CrossRef
68.
Ma J, Li J, Li H, Xiao X, Shen L, Fang L. Downregulation of pancreatic-duodenal homeobox 1 expression in breast cancer patients: a mechanism of proliferation and apoptosis in cancer. Mol Med Rep. 2012;6:983–8.PubMed
69.
Urruticoechea A, Smith IE, Dowsett M. Proliferation marker Ki-67 in early breast cancer. J Clin Oncol. 2005;23:7212–20.CrossRefPubMed
Metadata
Title
Deregulation of base excision repair gene expression and enhanced proliferation in head and neck squamous cell carcinoma
Authors
Ishrat Mahjabeen
Kashif Ali
Xiaofeng Zhou
Mahmood Akhtar Kayani
Publication date
01-06-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 6/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-1792-5

Other articles of this Issue 6/2014

Tumor Biology 6/2014 Go to the issue

Research Article

ARID1A is downregulated in non-small cell lung cancer and regulates cell proliferation and apoptosis

Research Article

The effect of RAD51 135 G>C and XRCC2 G>A (rs3218536) polymorphisms on ovarian cancer risk among Caucasians: a meta-analysis

Research Article

RETRACTED ARTICLE: Canine transmissible venereal tumor and seminoma: a cytohistopathology and chemotherapy study of tumors in the growth phase and during regression after chemotherapy

Research Article

Increased FAT10 expression is related to poor prognosis in pancreatic ductal adenocarcinoma

Research Article

MDM2 SNP309 variation increases cervical cancer risk among Asians

Research Commentary

Comment on Jiang G. et al.: Efficacy and safety between temozolomide alone and temozolomide-based double therapy for malignant melanoma: a meta-analysis
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits