Expression of P-EGFR and P-Akt protein in esophageal squamous cell carcinoma and its prognosis

Shan,Zheng-Zheng; Chen,Pei-Nan; Wang,Feng; Wang,Jun; Fan,Qing-Xia

doi:10.3892/ol.2017.6526

Expression of P-EGFR and P-Akt protein in esophageal squamous cell carcinoma and its prognosis

Authors:
- Zheng-Zheng Shan
- Pei-Nan Chen
- Feng Wang
- Jun Wang
- Qing-Xia Fan
View Affiliations

Affiliations: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Oncology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: July 6, 2017 https://doi.org/10.3892/ol.2017.6526
Pages: 2859-2863
Copyright: © Shan 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

The phosphorylated epidermal growth factor receptor (P-EGFR) and phosphorylated Akt (P-Akt) protein in esophageal squamous cell carcinoma (ESCC) were studied, and its significance in clinical prognosis of patients was assessed. The expression of P-EGFR and P-Akt protein in 83 cases of ESCC and 83 normal esophageal tissues was determined by immunohistochemical staining. Log-rank test and correlation analysis were used to analyze the prognosis of ESCC. The positive expression of P-EGFR in ESCC was 88% (73/83 cases) compared with 41% in normal esophageal mucosa (34/83 cases) (P<0.05). The rate of P-Akt protein expression in ESCC was 90.4% (75/83 cases), compared with 27.7% seen in normal esophageal mucosa (23/83 cases) (P<0.05). The expression of P-EGFR and P-Akt protein was positively correlated with lymph node metastasis and degree of differentiation (P<0.05) irrespective of sex, age, tumor diameter and TNM stage (P>0.05). The expression of P-EGFR was positively correlated with that of P-Akt protein (r=0.674, P<0.01). P-EGFR expression was negatively correlated with survival time of patients with ESCC (r=-0.526, P<0.01). The Kaplan-Meier survival curves showed that the cumulative survival rate of P-EGFR‑positive cases was significantly lower than that of the P-EGFR-negative cases (P<0.01). The expression of P-Akt was negatively correlated with survival in patients with ESCC (r=-0.473, P<0.01). The Kaplan‑Meier survival curves showed that the cumulative survival rate of the P-Akt-positive cases was significantly lower than that of the P-Akt-negative cases (P<0.01). In conclusion, P-EGFR and P-Akt protein expression is closely related to the incidence of ESCC and mediates the development of invasive cancer and metastasis. It is used to determine the prognosis of ESCC, and may represent a new therapeutic target for the disease.

View Figures

View References

1	Aleskandarany MA, Rakha EA, Ahmed MA, Powe DG, Ellis IO and Green AR: Clinicopathologic and molecular significance of phospho-Akt expression in early invasive breast cancer. Breast Cancer Res Treat. 127:407–416. 2011. View Article : Google Scholar : PubMed/NCBI
2	Hembrough T, Thyparambil S, Liao WL, Darfler MM, Abdo J, Bengali KM, Taylor P, Tong J, Lara-Guerra H, Waddell TK, et al: Selected reaction monitoring (SRM) analysis of epidermal growth factor receptor (EGFR) in formalin fixed tumor tissue. Clin Proteomics. 9:52012. View Article : Google Scholar : PubMed/NCBI
3	Abdulwahab A, Sykes J, Kamel-Reid S, Chang H and Brandwein JM: Therapy-related acute lymphoblastic leukemia is more frequent than previously recognized and has a poor prognosis. Cancer. 118:3962–3967. 2012. View Article : Google Scholar : PubMed/NCBI
4	Licitra L, Störkel S, Kerr KM, Van Cutsem E, Pirker R, Hirsch FR, Vermorken JB, von Heydebreck A, Esser R, Celik I, et al: Predictive value of epidermal growth factor receptor expression for first-line chemotherapy plus cetuximab in patients with head and neck and colorectal cancer: analysis of data from the EXTREME and CRYSTAL studies. Eur J Cancer. 49:1161–1168. 2013. View Article : Google Scholar : PubMed/NCBI
5	Jia M and Souchelnytstkyi S: Comments on the cross-talk of TGFβ and EGF in cancer. Exp Oncol. 33:170–173. 2011.PubMed/NCBI
6	Mints M and Souchelnytskyi S: Impact of combinations of EGF, TGFβ, 17β-oestradiol, and inhibitors of corresponding pathways on proliferation of breast cancer cell lines. Exp Oncol. 36:67–71. 2014.PubMed/NCBI
7	Cree IA: Designing personalised cancer treatments. J Control Release. 172:405–409. 2013. View Article : Google Scholar : PubMed/NCBI
8	Moghadamtousi SZ, Kadir HA, Paydar M, Rouhollahi E and Karimian H: Annona muricata leaves induced apoptosis in A549 cells through mitochondrial-mediated pathway and involvement of NF-κB. BMC Complement Altern Med. 14:2992014. View Article : Google Scholar : PubMed/NCBI
9	Asare GA, Afriyie D, Ngala RA, Abutiate H, Doku D, Mahmood SA and Rahman H: Antiproliferative activity of aqueous leaf extract of Annona muricata L. on the prostate, BPH-1 cells, and some target genes. Integr Cancer Ther. 14:65–74. 2015. View Article : Google Scholar : PubMed/NCBI
10	Mimeault M and Batra SK: Frequent gene products and molecular pathways altered in prostate cancer- and metastasis-initiating cells and their progenies and novel promising multitargeted therapies. Mol Med. 17:949–964. 2011. View Article : Google Scholar : PubMed/NCBI
11	Mimeault M, Johansson SL and Batra SK: Pathobiological implications of the expression of EGFR, pAkt, NF-κB and MIC-1 in prostate cancer stem cells and their progenies. PLoS One. 7:e319192012. View Article : Google Scholar : PubMed/NCBI
12	Llovet P, Sastre J, Ortega JS, Bando I, Ferrer M, García-Alfonso P, Donnay O, Carrato A, Jiménez A, Aranda E, et al: Prognostic value of BRAF PI3K, PTEN, EGFR copy number, amphiregulin and epiregulin status in patients with KRAS codon 12 wild-type metastatic colorectal cancer receiving first-line chemotherapy with anti-EGFR therapy. Mol Diagn Ther. 19:397–408. 2015. View Article : Google Scholar : PubMed/NCBI
13	Pentheroudakis G, Kotoula V, De Roock W, Kouvatseas G, Papakostas P, Makatsoris T, Papamichael D, Xanthakis I, Sgouros J, Televantou D, et al: Biomarkers of benefit from cetuximab-based therapy in metastatic colorectal cancer: interaction of EGFR ligand expression with RAS/RAF, PIK3CA genotypes. BMC Cancer. 13:492013. View Article : Google Scholar : PubMed/NCBI
14	Loupakis F, Cremolini C, Fioravanti A, Orlandi P, Salvatore L, Masi G, Schirripa M, Di Desidero T, Antoniotti C, Canu B, et al: EGFR ligands as pharmacodynamic biomarkers in metastatic colorectal cancer patients treated with cetuximab and irinotecan. Target Oncol. 9:205–214. 2014. View Article : Google Scholar : PubMed/NCBI
15	Petrelli F, Borgonovo K and Barni S: The predictive role of skin rash with cetuximab and panitumumab in colorectal cancer patients: a systematic review and meta-analysis of published trials. Target Oncol. 8:173–181. 2013. View Article : Google Scholar : PubMed/NCBI
16	Li P, Yang R and Gao WQ: Contributions of epithelial-mesenchymal transition and cancer stem cells to the development of castration resistance of prostate cancer. Mol Cancer. 13:552014. View Article : Google Scholar : PubMed/NCBI
17	Pan Y, Zhang Y, Li Y, Hu H, Wang L, Li H, Wang R, Ye T, Luo X, Zhang Y, et al: Prevalence, clinicopathologic characteristics, and molecular associations of EGFR exon 20 insertion mutations in East Asian patients with lung adenocarcinoma. Ann Surg Oncol. 21 Suppl 4:S490–S496. 2014. View Article : Google Scholar : PubMed/NCBI
18	Cheng L, Ren W, Xie L, Li M, Liu J, Hu J, Liu BR and Qian XP: Anti-EGFR MoAb treatment in colorectal cancer: limitations, controversies, and contradictories. Cancer Chemother Pharmacol. 74:1–13. 2014. View Article : Google Scholar : PubMed/NCBI
19	Nishikawa M, Miyake H and Masato F: Enhanced sensitivity to sunitinib by inhibition of Akt-1 expression in human castration-resistant prostate cancer PC3 cells both in vitro and in vivo. Mol Cancer Ther. 13:1949–1960. 2014.