EGFR/PI3K/Akt/mTOR pathway in head and neck squamous cell carcinoma patients with different HPV status

Abstract

The aim of the study was to compare prognostic potential of PIK3CA mutations and expression of proteins involved in or regulate EGFR/PI3K/Akt/mTOR signaling in HPV16 positive and HPV negative head and neck squamous cell carcinoma (HNSCC) patients. The expression of proteins (EGFR, Akt, pAkt(Ser473), pAkt(Thr308), mTOR, PTEN, pPTEN, APOBEC3B) were assessed immunohistochemically and PIK3CA mutations (p.E542K, p.E545K, p.H1047R) by qPCR. Significantly more HPV16 positive tumors (89.29%) with low EGFR expression were found as compared to HPV negative ones (58.82%). PIK3CA mutations were detected in 7.14% of HPV16 positive and 2.5% of HPV negative cancers. In HPV16 positive patients survival analysis has shown that positive prognostic potential for disease free survival (DFS) had low expression of APOBEC3B. In HPV negative patients prognostic significance for DFS had APOBEC3B, Akt and pAkt(Thr308) levels, and for overall survival (OS) -pAkt(Thr308) only. Independent favorable prognostic factors in the whole group of patients were: low T stage, low pAkt(Thr308) expression, active HPV16 infection (for OS and DFS) and female gender (for OS). Obtained results suggest the existence of significant differences in expression and prognostic potential of proteins involved in EGFR/PI3K/Akt/mTOR signaling between HPV16 positive and HPV negative HNSCC patients.

Network pharmacology prediction and molecular docking-based strategy to explore the potential mechanism of RSG and Phellodendron against HPV infection

“…And it was found that HPV (+) infected was associated with EGFR expression only, and that the higher the tumor grade, the more signi cant the high expression of EGFR. As the negative upstream regulators of mTOR [49] , PTEN inhibit the production of mTOR, negatively regulates the PI3K/AKT/mTOR pathway [ 50] , then PTEN reverse the production of PIP3 [ 51] .Therefore, PTEN expression is mostly down-regulated or absent in HPV-related cancers [ 52] . Some reports have shown no signi cant difference in the expression of mTOR, pPTEN, and PTEN between HPV (+) and HPV (-) patients.…”

Revealing the Preventable Effects of Fu-Zheng-Qu-Xie Decoction against Recurrence and Metastasis of Postoperative Early-Stage Lung Adenocarcinoma Based on Network Pharmacology Coupled with Metabolomics Analysis

“…EGFR is a kind of proto-oncogene and is associated with tumor cell growth, metastasis, invasion, epithelial–mesenchymal transition (EMT), angiogenesis, drug resistance, immune regulation, and stem cell maintenance. Growing evidence suggests that EGFR causes different signal responses in cells through phosphorylation of cytoplasmic tyrosine kinase and binding with downstream signal pathways, including PI3K/AKT, JAK/STAT, and RAS/RAF/MAPK. − In addition, upon cancer initiation and formation, Akt mutation activates downstream signaling pathways, resulting in cancer immune tolerance and escape from classical immune attack. − Akt is a serine/threonine kinase of the AGC family, including the Akt1, Akt2, and Akt3 isoforms. Akt1 was initially found to be a proto-oncogene that plays an essential role in regulating various cell functions .…”

Cancer Cell Metabolism Reprogramming and Its Potential Implications on Therapy in Squamous Cell Carcinoma of the Head and Neck: A Review

“…Loss of PTEN expression is described in about 30% of oral cavity cancers, and loss of heterozygosity (LOH) is identified in 40% of SCCHNs. As a result, AKT activation results in an up-regulation of glycolysis, PPP, biosynthesis of fatty acids, nucleotides, and proteins favoring metabolic reprogramming [ 35 , 36 ].…”