Thyroid hormone receptor \u03b11 acts as a new squamous cell lung cancer diagnostic marker and poor prognosis predictor

Fatma El Zahraa A Mohamed,Ali Omar Abdelaziz,Tarek Ellethy,Ahmed Hussein Kasem,Mariana F Gayyed

doi:10.1038/s41598-021-86754-6

Fatma El Zahraa A Mohamed, Ali Omar Abdelaziz + Show 3 more

Open Access

https://doi.org/10.1038/s41598-021-86754-6

Copy DOI

Abstract

Lung cancer is considered the major cause of cancer-related deaths worldwide. Unfortunately, all chemotherapy regimens used in lung cancer treatment showed nearly the same efficacy. Finding a new therapeutic target that can be used as an alternative after the failure of or in association with chemotherapy to improve the prognosis is an urgent demand. Up to date, it is Known that thyroid hormones (THs) and Thyroid hormone receptors (THRs) control the progression of several types of tumours. Nevertheless, their role in non-small cell lung cancer (NSCLC) is unknown. This study investigated the expression of THRα1 in NSCLC cases and its correlation to tumour clinicopathological parameters to shed new light on the relevance of THRα1 in lung cancer. Immunohistochemistry utilizing THRα1 antibody was performed on tissue sections obtained from 80 patients diagnosed with NSCLC. We also investigated the expression of THRα gene in Microarrays of lung squamous cell carcinoma (SCC) and adenocarcinoma (AC) patients by using GEO data sets on https://www.ncbi.nlm.nih.gov. We showed, for the first time, the expression of THRα1 in NSCLC. Intermediate and high THRα1 expressions were detected in (25% and 66.7%) of SCC cases respectively. High THRα1 expression was associated with shorter OS. On the other hand, 86.7% of AC cases revealed low THRα1 expression. Inflammatory cells in SCC cases showed high THRα1 expression. By analysing GEO data sets, a significant increase in THRα gene expression was found in SCC compared to AC cases. Our study underscores the possibility of using THRα1 expression not only as a prognostic marker, but also as an innovative diagnostic additive tool for lung SCC, which could be tested as a potential therapeutic target for SCC in the future.

Highlights

Lung cancer is considered the major cause of cancer-related deaths worldwide
We investigated the expression of thyroid hormone receptor α gene values in squamous cell carcinoma (SCC) and AD patients from previous gene microarray studies by using Gene Expression Omnibus database (GEO) data sets on https://www.ncbi.nlm.nih.gov
THRα1 expression was detected in the cytoplasm of Non-small cell lung carcinoma (NSCLC) but not in normal lung tissue as shown in (Fig. 1)

Summary

Introduction

Lung cancer is considered the major cause of cancer-related deaths worldwide. all chemotherapy regimens used in lung cancer treatment showed nearly the same efficacy. It is Known that thyroid hormones (THs) and Thyroid hormone receptors (THRs) control the progression of several types of tumours Their role in non-small cell lung cancer (NSCLC) is unknown. The S2 site can bind binds T4 as well as with a lower affinity T3 leading to activation of the ERK1/2 pathway[12] In this way, αvβ[3] integrin binding promotes the hormones’ proliferative effect on cancer cells through a non-genomic pathway. In NSCLC, physiological concentrations of T4 facilitated internalization as well as nuclear translocation of the integrin αv monomer that binds inside the cell nucleus promoters of central cancer-related genes, such as thyroid hormone receptor β1, ERα and cyclooxygenase-2 and hypoxia-inducible factor-1α (HIF1α)[15]. A significant association was revealed between the expression of THRα1, tumour size and tumour s tage[19]

Objectives

Methods

Results

Conclusion