Ki‑67 is overexpressed in human laryngeal carcinoma and contributes to the proliferation of HEp2 cells

Bai,Yanxia; Shao,Yuan; Li,Huajing; Xue,Wanli; Quan,Fang; Wu,Shengli

doi:10.3892/ol.2016.4980

Ki‑67 is overexpressed in human laryngeal carcinoma and contributes to the proliferation of HEp2 cells

Authors:
- Yanxia Bai
- Yuan Shao
- Huajing Li
- Wanli Xue
- Fang Quan
- Shengli Wu
View Affiliations

Affiliations: Department of Otorhinolaryngology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Public Health, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, P.R. China, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: August 8, 2016 https://doi.org/10.3892/ol.2016.4980
Pages: 2641-2647
Copyright: © Bai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Ki-67 is one of the most useful markers to evaluate cell proliferative activity and has been widely used in tumor treatment and research. However, its role in human laryngeal carcinoma remains poorly defined. The aim of the present study was to investigate the expression of Ki‑67 in human laryngeal squamous carcinoma and the effect of Ki‑67 gene silencing by small interfering (si)RNA on the proliferation of human laryngocarcinoma HEp2 cells. Immunohistochemistry and reverse transcription‑quantitative polymerase chain reaction were performed to examine the expression of Ki‑67 in human laryngeal squamous carcinoma tissues and adjacent non‑cancer tissues from 50 patients with laryngeal squamous carcinoma. RNA interference was used to knock down the expression of Ki‑67 in the HEp2 cell line, and the proliferation of the treated cells was observed in vitro. Western blot analysis was used to determine the expression levels of epidermal growth factor receptor (EGFR) and E‑cadherin in the treated cells. The expression of Ki‑67 in the laryngeal squamous carcinoma tissues was significantly higher than that of the adjacent non‑tumor tissues (P=0.028). The high expression of Ki‑67 in cancer was significantly correlated with cervical lymph node metastasis and clinical outcomes (all P<0.001). The silencing of Ki‑67 resulted in the inhibition of proliferation of the HEp2 human laryngocarcinoma cells (P<0.001). In addition, compared with the control group, the expression levels of EGFR and E‑cadherin in the Ki‑67 siRNA‑treated cells were significantly decreased (P<0.001) and increased (P<0.001), respectively. These results suggested that Ki‑67 is important in regulating the proliferation of human laryngocarcinoma HEp2 cells and that the mechanism may at least partially be associated with the upregulation of EGFR and the downregulation of E‑cadherin. Overall, Ki‑67 can be used as an important indicator for judging clinical progress and estimating prognosis in human laryngeal squamous carcinoma.

View Figures

View References

1	Markou K, Christoforidou A, Karasmanis I, Tsiropoulos G, Triaridis S, Constantinidis I, Vital V and Nikolaou A: Laryngeal cancer: Epidemiological data from Νorthern Greece and review of the literature. Hippokratia. 17:313–318. 2013.PubMed/NCBI
2	Iovănescu GH, Poenaru M, Doroş C and Borugă O: Histopathological prognostic and risk factors in patients with laryngeal neoplasms. Rom J Morphol Embryol. 54:1087–1092. 2013.PubMed/NCBI
3	Traoré CB, Kamaté B, Kéita M, Tchoupa MM, Timbo SK, Ag MA and Bayo S: Laryngo-pharyngeal cancer at a health service of last resort in Mali: Anatomo-clinical and therapeutic aspects. Mali Med. 23:51–54. 2008.(In French).
4	Arshad H, Ahmad Z and Hasan SH: Gliomas: Correlation of histologic grade, Ki67 and p53 expression with patient survival. Asian Pac J Cancer Prev. 11:1637–1640. 2010.PubMed/NCBI
5	Klintman M, Bendahl PO, Graban D, Lövgren K, Malmström P and Fernö M: South Sweden Breast Cancer Group: The prognostic value of Ki67 is dependent on estrogen receptor status and histological grade in premenopausal patients with node-negative breast cancer. Mod Pathol. 23:251–259. 2010. View Article : Google Scholar : PubMed/NCBI
6	Tadbir AA, Pardis S, Ashkavandi ZJ, Najvani AD, Ashraf MJ, Taheri A, Zadeh MA and Sardari Y: Expression of Ki67 and CD105 as proliferation and angiogenesis markers in salivary gland tumors. Asian Pac J Cancer Prev. 13:5155–5159. 2012. View Article : Google Scholar : PubMed/NCBI
7	Naderi N Jalayer, Tirgari F, Kharazi-Fard MJ and Parsa F Farahani: A study on the relationship between clinical features with Ki67 expression and eosinophil cells infiltration in oral squamous cell carcinoma. Med J Islam Repub Iran. 28:1152014.PubMed/NCBI
8	Thompson L: World Health Organization classification of tumours: pathology and genetics of head and neck tumours. Ear Nose Throat J. 85:742006.PubMed/NCBI
9	Schmittgen TD and Livak KJ: Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 3:1101–1108. 2008. View Article : Google Scholar : PubMed/NCBI
10	Edge SB and Compton CC: The American Joint Committee on Cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17:1471–1474. 2010. View Article : Google Scholar : PubMed/NCBI
11	Zhou Y, Jiang HG, Lu N, Lu BH and Chen ZH: Expression of ki67 in papillary thyroid microcarcinoma and its clinical significance. Asian Pac J Cancer Prev. 16:1605–1608. 2015. View Article : Google Scholar : PubMed/NCBI
12	Li LT, Jiang G, Chen Q and Zheng JN: Ki67 is a promising molecular target in the diagnosis of cancer (review). Mol Med Rep. 11:1566–1572. 2015.PubMed/NCBI
13	Liu HB, Gao XX, Zhang Q, Liu J, Cui Y, Zhu Y and Liu YF: Expression and prognostic implications of FOXO3a and Ki67 in lung adenocarcinomas. Asian Pac J Cancer Prev. 16:1443–1448. 2015. View Article : Google Scholar : PubMed/NCBI
14	Chen LY, Tsang JY, Ni YB, Chan SK, Chan KF, Zhang S and Tse GM: Bcl2 and Ki67 refine prognostication in luminal breast cancers. Breast Cancer Res Treat. 149:631–643. 2015. View Article : Google Scholar : PubMed/NCBI
15	Beuschlein F, Weigel J, Saeger W, Kroiss M, Wild V, Daffara F, Libé R, Ardito A, Al Ghuzlan A, Quinkler M, et al: Major prognostic role of ki67 in localized adrenocortical carcinoma after complete resection. J Clin Endocrinol Metab. 100:841–849. 2015. View Article : Google Scholar : PubMed/NCBI
16	Li N, Deng W, Ma J, Wei B, Guo K, Shen W, Zhang Y and Luo S: Prognostic evaluation of Nanog, Oct4, Sox2, PCNA, Ki67 and E-cadherin expression in gastric cancer. Med Oncol. 32:4332015. View Article : Google Scholar : PubMed/NCBI
17	Leopardi G, Serafini G, Simoncelli C, Ludovini V, Pistola L and Altissimi G: Ki67 and p53 in laryngeal epithelial lesions: Correlations with risk factors. Acta Otorhinolaryngeal Ital. 21:243–247. 2001.(In Italian).
18	Liu M, Lawson G, Delos M, Jamart J, Chatelain B, Remacle M and Marbaix E: Prognostic value of cell proliferation markers, tumour suppressor proteins and cell adhesion molecules in primary squamous cell carcinoma of the larynx and hypopharynx. Eur Arch Otorhinolaryngol. 260:28–34. 2003.PubMed/NCBI
19	Teppo H, Soini Y, Melkko J, Koivunen P and Alho OP: Prognostic factors in laryngeal carcinoma: The role of apoptosis, p53, proliferation (Ki-67) and angiogenesis. APMIS. 111:451–457. 2003. View Article : Google Scholar : PubMed/NCBI
20	Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, Carotenuto A, De Feo G, Caponigro F and Salomon DS: Epidermal growth factor receptor (EGFR) signaling in cancer. Gene. 366:2–16. 2006. View Article : Google Scholar : PubMed/NCBI
21	Buckley AF, Burgart LJ, Sahai V and Kakar S: Epidermal growth factor receptor expression and gene copy number in conventional hepatocellular carcinoma. Am J Clin Pathol. 129:245–251. 2008. View Article : Google Scholar : PubMed/NCBI
22	Carcereny E, Morán T, Capdevila L, Cros S, Vilà L, de Los Llanos Gil M, Remón J and Rosell R: The epidermal growth factor receptor (EGRF) in lung cancer. Transl Respir Med. 3:12015. View Article : Google Scholar : PubMed/NCBI
23	Carlsson J, Wester K, De La Torre M, Malmström PU and Gårdmark T: EGFR-expression in primary urinary bladder cancer and corresponding metastases and the relation to HER2-expression. On the possibility to target these receptors with radionuclides. Radiol Oncol. 49:50–58. 2015. View Article : Google Scholar : PubMed/NCBI
24	Li F, Kang N, Fu W, Sun X, Gao H and Sun K: Detection of epidermal growth factor receptor gene amplification in human laryngeal carcinomas by means of fluorescence in situ hybridization. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 17:278–280. 2000.(In Chinese). PubMed/NCBI
25	Li M, Wei M, Jiang Z, Wei H, Lu W, Dou W and Lu S: BRAF overexpression induces rampant glioma proliferation independent of phospho-EGFR expression. Adv Clin Exp Med. 23:893–899. 2014. View Article : Google Scholar : PubMed/NCBI
26	Yang Y, Xuan J, Yang Z, Han A, Xing L, Yue J, Hu M and Yu J: The expression of epidermal growth factor receptor and Ki67 in primary and relapse nasopharyngeal cancer: A micro-evidence for anti-EGFR targeted maintenance therapy. Med Oncol. 29:1448–1455. 2012. View Article : Google Scholar : PubMed/NCBI
27	Onder TT, Gupta PB, Mani SA, Yang J, Lander ES and Weinberg RA: Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res. 68:3645–3654. 2008. View Article : Google Scholar : PubMed/NCBI
28	Nakagawa Y, Ohira M, Kubo N, Yamashita Y, Sakurai K, Toyokawa T, Tanaka H, Muguruma K, Shibutani M, Yamazoe S, et al: Tumor budding and E-cadherin expression are useful predictors of nodal involvement in T1 esophageal squamous cell carcinoma. Anticancer Res. 33:5023–5029. 2013.PubMed/NCBI
29	Rodrigo JP, Dominguez F, Alvarez C, Manrique C, Herrero A and Suárez C: Expression of E-cadherin in squamous cell carcinomas of supraglottic larynx with correlations to clinicopathological features. Eur J Cancer. 38:1059–1064. 2002. View Article : Google Scholar : PubMed/NCBI
30	Simionescu C, Mărgăritescu C, Stepan A, Georgescu CV, Niculescu M and Muntean M: The utility of p16, E-cadherin and Ki67 in cervical squamous intraepithelial lesions diagnosis. Rom J Morphol Embryol. 51:621–626. 2010.PubMed/NCBI