Analysis of changes in the expression of Notch1 and HES1 and the prognosis of osteosarcoma patients following surgery

Fang,Long; Li,Bei; Yu,Dapeng; Wang,Baolong; Zhao,Tingbao

doi:10.3892/ol.2020.11890

Analysis of changes in the expression of Notch1 and HES1 and the prognosis of osteosarcoma patients following surgery

Authors:
- Long Fang
- Bei Li
- Dapeng Yu
- Baolong Wang
- Tingbao Zhao
View Affiliations

Affiliations: Department of Orthopaedics, Shangdong Provincial Third Hospital, Cheeloo College of Medicine, Shangdong University, Jinan, Shandong 250000, P.R. China, Department of Orthopaedics, Shangdong Provincial Western Hospital, Jinan, Shandong 250000, P.R. China
Published online on: July 17, 2020 https://doi.org/10.3892/ol.2020.11890
Article Number: 29

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

The present study aimed to analyze the changes in the expression of Notch1 and hairy and enhancer of split‑1 (HES1) and the prognosis of patients with osteosarcoma following surgery. Samples from 62 patients with osteosarcoma treated at Shandong Cancer hospital from April, 2011 to June, 2013 were collected as the research group, and those from 52 healthy individuals undergoing physical examination were collected as the control group. The expression levels of Notch1 and HES1 in the serum of patients with osteosarcoma were measured by ELISA before and after surgery. Pearson's correlation analysis was used to analyze the correlation between Notch1 expression and HES1 expression in the osteosarcoma patients. According to the expression levels of Notch1 and HES1, the patients were divided into the high expression group and the low expression group, and the 5‑year survival rate of the patients was observed. The expression levels of Notch1 and HES1 in the osteosarcoma patients before surgery were higher than those after surgery (P<0.05). The sensitivity, specificity and AUC of Notch1 for osteosarcoma were 93.55%, 58.06% and 0.732 respectively, and those of HES1 were 82.26%, 61.29% and 0.766, respectively. The expression level of Notch1 positively correlated with the expression level of HES1 in the osteosarcoma patients (r=0.795, P<0.001). According to the expression levels of Notch1 and HES1, the patients were divided into the high and low expression groups. The survival rate of the low expression group was significantly higher than that of the high expression groups (P=0.045). Finally, multiple factors were analyzed by logistic regression, and it was found that tumor location, chemotherapy response, tumor size, Notch1 and HES1 were independent risk factors for prognosis. Notch1 and HES1 exhibited a low expression in patients following surgery. ROC curve analysis revealed that the two indicators had good diagnostic efficacy and were expected to become markers for diagnosis and prognosis of osteosarcoma.

View Figures

View References

1	Moore DD and Luu HH: Osteosarcoma. Cancer Treat Res. 162:65–92. 2014. View Article : Google Scholar : PubMed/NCBI
2	Harrison DJ, Geller DS, Gill JD, Lewis VO and Gorlick R: Current and future therapeutic approaches for osteosarcoma. Expert Rev Anticancer Ther. 18:39–50. 2018. View Article : Google Scholar : PubMed/NCBI
3	Ottaviani G and Jaffe N: The epidemiology of osteosarcoma. Pediatric and adolescent osteosarcoma. Cancer Treat Res. 152:3–13. 2009. View Article : Google Scholar : PubMed/NCBI
4	Lamora A, Talbot J, Bougras G, Amiaud J, Leduc M, Chesneau J, Taurelle J, Stresing V, Le Deley MC, Heymann MF, et al: Overexpression of smad7 blocks primary tumor growth and lung metastasis development in osteosarcoma. Clin Cancer Res. 20:5097–5112. 2014. View Article : Google Scholar : PubMed/NCBI
5	Artavanis-Tsakonas S, Rand MD and Lake RJ: Notch signaling: Cell fate control and signal integration in development. Science. 284:770–776. 1999. View Article : Google Scholar : PubMed/NCBI
6	Pece S, Serresi M, Santolini E, Capra M, Hulleman E, Galimberti V, Zurrida S, Maisonneuve P, Viale G and Di Fiore PP: Loss of negative regulation by Numb over Notch is relevant to human breast carcinogenesis. J Cell Biol. 167:215–221. 2004. View Article : Google Scholar : PubMed/NCBI
7	Li Y, Zhang J, Ma D, Zhang L, Si M, Yin H and Li J: Curcumin inhibits proliferation and invasion of osteosarcoma cells through inactivation of Notch-1 signaling. FEBS J. 279:2247–2259. 2012. View Article : Google Scholar : PubMed/NCBI
8	Diévart A, Beaulieu N and Jolicoeur P: Involvement of Notch1 in the development of mouse mammary tumors. Oncogene. 18:5973–5981. 1999. View Article : Google Scholar : PubMed/NCBI
9	Garber K: Notch emerges as new cancer drug target. J Natl Cancer Inst. 99:1284–1285. 2007. View Article : Google Scholar : PubMed/NCBI
10	Wang SC, Lin XL, Wang HY, Qin YJ, Chen L, Li J, Jia JS, Shen HF, Yang S, Xie RY, et al: Hes1 triggers epithelial-mesenchymal transition (EMT)-like cellular marker alterations and promotes invasion and metastasis of nasopharyngeal carcinoma by activating the PTEN/AKT pathway. Oncotarget. 6:36713–36730. 2015. View Article : Google Scholar : PubMed/NCBI
11	Candy PA, Phillips MR, Redfern AD, Colley SM, Davidson JA, Stuart LM, Wood BA, Zeps N and Leedman PJ: Notch-Induced transcription factors are predictive of survival and 5-fluorouracil response in colorectal cancer patients. Br J Cancer. 109:1023–1030. 2013. View Article : Google Scholar : PubMed/NCBI
12	Farnie G, Clarke RB, Spence K, Pinnock N, Brennan K, Anderson NG and Bundred NJ: Novel cell culture technique for primary ductal carcinoma in situ: Role of Notch and epidermal growth factor receptor signaling pathways. J Natl Cancer Inst. 99:616–627. 2007. View Article : Google Scholar : PubMed/NCBI
13	Konishi J, Kawaguchi KS, Vo H, Haruki N, Gonzalez A, Carbone DP and Dang TP: Gamma-secretase inhibitor prevents Notch3 activation and reduces proliferation in human lung cancers. Cancer Res. 67:8051–8057. 2007. View Article : Google Scholar : PubMed/NCBI
14	Bielack S, Carrle D and Casali PG; ESMO Guidelines Working Group, : Osteosarcoma: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 20 (Suppl 4):S137–S139. 2009. View Article : Google Scholar
15	Ando K, Heymann MF, Stresing V, Mori K, Rédini F and Heymann D: Current therapeutic strategies and novel approaches in osteosarcoma. Cancers (Basel). 5:591–616. 2013. View Article : Google Scholar : PubMed/NCBI
16	Sampson VB, Yoo S, Kumar A, Vetter NS and Kolb EA: MicroRNAs and potential targets in osteosarcoma: Review. Front Pediatr. 3:692015. View Article : Google Scholar : PubMed/NCBI
17	Zhao H, Yao Y, Wang Z, Lin F, Sun Y and Chen P: Therapeutic effect of pirarubicin-based chemotherapy for osteosarcoma patients with lung metastasis. J Chemother. 22:119–124. 2010. View Article : Google Scholar : PubMed/NCBI
18	He A, Yang X, Huang Y, Feng T, Wang Y, Sun Y, Shen Z and Yao Y: CD133(+) CD44(+) cells mediate in the lung metastasis of osteosarcoma. J Cell Biochem. 116:1719–1729. 2015. View Article : Google Scholar : PubMed/NCBI
19	Daw NC, Chou AJ, Jaffe N, Rao BN, Billups CA, Rodriguez- Galindo C, Meyers PA and Huh WW: Recurrent osteosarcoma with a single pulmonary metastasis: A multi-institutional review. Br J Cancer. 112:278–282. 2015. View Article : Google Scholar : PubMed/NCBI
20	Faisham WI, Mat Saad AZ, Alsaigh LN, Nor Azman MZ, Kamarul Imran M, Biswal BM, Bhavaraju VM, Salzihan MS, Hasnan J, Ezane AM, et al: Prognostic factors and survival rate of osteosarcoma: A single-institution study. Asia Pac J Clin Oncol. 13:e104–e110. 2017. View Article : Google Scholar : PubMed/NCBI
21	Chen J, Ma L and Wei G: Comment on Fu et al.: A systematic review of p53 as a biomarker of survival in patients with osteosarcoma. Tumour Biol. 35:5049–5050. 2014. View Article : Google Scholar : PubMed/NCBI
22	Shin SH, Jeong HJ, Han I, Cho HS and Kim HS: Osteosarcoma and chondrosarcoma of the shoulder: Site-Specific comparative analysis. Orthopedics. 36:e179–e185. 2013. View Article : Google Scholar : PubMed/NCBI
23	He H, Ni J and Huang J: Molecular mechanisms of chemoresistance in osteosarcoma (Review). Oncol Lett. 7:1352–1362. 2014. View Article : Google Scholar : PubMed/NCBI
24	Miele L: Notch signaling. Clin Cancer Res. 12:1074–1079. 2006. View Article : Google Scholar : PubMed/NCBI
25	Chiba S: Notch signaling in stem cell systems. Stem Cells. 24:2437–2447. 2006. View Article : Google Scholar : PubMed/NCBI
26	Villanueva A, Alsinet C, Yanger K, Hoshida Y, Zong Y, Toffanin S, Rodriguez-Carunchio L, Solé M, Thung S, Stanger BZ and Llovet JM: Notch signaling is activated in human hepatocellular carcinoma and induces tumor formation in mice. Gastroenterology. 143:1660–1669.e7. 2012. View Article : Google Scholar : PubMed/NCBI
27	Bocchicchio S, Tesone M and Irusta G: Convergence of wnt and notch signaling controls ovarian cancer cell survival. J Cell Physiol. 234:22130–22143. 2019. View Article : Google Scholar : PubMed/NCBI
28	Lai XX, Li G, Lin B and Yang H: Interference of Notch 1 inhibits the proliferation and invasion of breast cancer cells: Involvement of the β-catenin signaling pathway. Mol Med Rep. 17:2472–2478. 2018.PubMed/NCBI
29	Takebayashi K, Sasai Y, Sakai Y, Watanabe T, Nakanishi S and Kageyama R: Structure, chromosomal locus, and promoter analysis of the gene encoding the mouse helix-loop-helix factor HES-1. Negative autoregulation through the multiple N box elements. J Biol Chem. 269:5150–5156. 1994.PubMed/NCBI
30	Sasai Y, Kageyama R, Tagawa Y, Shigemoto R and Nakanishi S: Two mammalian helix-loop-helix factors structurally related to Drosophila hairy and enhancer of split. Genes Dev. 6:2620–2634. 1992. View Article : Google Scholar : PubMed/NCBI
31	Ishibashi M, Ang SL, Shiota K, Nakanishi S, Kageyama R and Guillemot F: Targeted disruption of mammalian hairy and Enhancer of split homolog-1 (HES-1) leads to up-regulation of neural helix-loop-helix factors, premature neurogenesis, and severe neural tube defects. Genes Dev. 9:3136–3148. 1995. View Article : Google Scholar : PubMed/NCBI
32	Ohtsuka T, Ishibashi M, Gradwohl G, Nakanishi S, Guillemot F and Kageyama R: Hes1 and Hes5 as notch effectors in mammalian neuronal differentiation. EMBO J. 18:2196–2207. 1999. View Article : Google Scholar : PubMed/NCBI
33	Zhang P, Yang Y, Zweidler-McKay PA and Hughes DP: Critical role of notch signaling in osteosarcoma invasion and metastasis. Clin Cancer Res. 14:2962–2969. 2008. View Article : Google Scholar : PubMed/NCBI