Significant Upregulation of HERV-K (HML-2) Transcription Levels in Human Lung Cancer and Cancer Cells

Caiqin Yang,Ziping Wang,Lin Li,Chengxi Sun,Yuyan Wang,Jingyun Li,Tongtong An,Lei Jia,Xiaolin Wang,Yujia Chi,Hong-Ling Wen,Jianjie Li,Hanping Li,Xin Guo,Jingwan Han,Bohan Zhang

doi:10.3389/fmicb.2022.850444

Abstract

Lung cancer is the second most common cancer worldwide and the leading cause of cancer death in the world. Therefore, there is an urgent need to develop new and effective biomarkers for diagnosis and treatment. Under this circumstance, human endogenous retroviruses (HERVs) were recently introduced as novel biomarkers for cancer diagnosis. This study focused on the correlation between lung cancer and HERV-K (HML-2) transcription levels. At the cellular level, different types of lung cancer cells and human normal lung epithelial cells were used to analyze the transcription levels of the HERV-K (HML-2) gag, pol, and env genes by RT–qPCR. At the level of lung cancer patients, blood samples with background information from 734 lung cancer patients and 96 healthy persons were collected to analyze the transcription levels of HERV-K (HML-2) gag, pol, and env genes. The results showed that the transcriptional levels of the HERV-K (HML-2) gag, pol, and env genes in lung cancer cells and lung cancer patient blood samples were significantly higher than those in the healthy controls, which was also verified by RNAScope ISH technology. In addition, we also found that there was a correlation between the abnormal transcription levels of HERV-K (HML-2) genes in lung cancer patients and the clinicopathological parameters of lung cancer. We also identified the distribution locations of the gag, pol, and env primer sequences on each chromosome and analyzed the function of these loci. In conclusion, HERV-K (HML-2) genes may be a potential biomarker for the diagnosis of lung cancer.

Highlights

Lung cancer, a bronchogenic malignancy originating from epithelial tissue (Wadowska et al, 2020), is the second most commonly diagnosed cancer and the leading cause of cancer deaths worldwide (Schwartz and Cote, 2016; Siegel et al, 2020)
Our results show that the occurrence of lung cancer is associated with human endogenous retroviruses (HERVs)-K (HML-2) gag, pol, and env, indicating that HERV-K (HML-2) genes may be a potential biomarker for the diagnosis of lung cancer
Analysis of the expression of HERV-K (HML-2) gag, pol, and env in lung cancers showed that the transcriptional levels of gag, pol, and env mRNA were significantly higher in small cell lung cancer (SCLC), adenocarcinoma, squamous cell carcinoma, and large cell carcinoma than in healthy controls (Figures 1D–F)

Summary

Introduction

A bronchogenic malignancy originating from epithelial tissue (Wadowska et al, 2020), is the second most commonly diagnosed cancer and the leading cause of cancer deaths worldwide (Schwartz and Cote, 2016; Siegel et al, 2020). According to the latest global cancer burden data for 2020 released by the International Agency for Research on Cancer (IARC) of the World Health Organization, in 2020, there were 2.2 million new cases of lung cancer worldwide (1.44 million males and 770,000 females), accounting for 11.4% of new cases of cancer (14.3% of males and 8.4% of females). The global number of lung cancer deaths was 1.8 million (1.19 million males and 610,000 females), accounting for 18% of cancer deaths (21.5% of males and 13.7% of females). The most common type of NSCLC includes three histological subtypes: adenocarcinoma (~50%), squamous cell carcinoma (~35%), and large cell carcinoma (~15%; Cagle et al, 2013)

Methods

Results

Conclusion