A Robust Panel Based on Mitochondrial Localized Proteins for Prognostic Prediction of Lung Adenocarcinoma

Weifeng Chen,Haohao Zhang,Dandan Liu,Deji Ye,Chaoyang Li,Donglin Sun,Qiumei Zhao,Xiaoren Zhang,Yongzhong Liu,Ningxia Xie,Jingyao Wang,Xianquan Zhan

doi:10.1155/2021/7569168

Abstract

Due to high energy and material metabolism requirements, mitochondria are frequently active in tumor cells. Our study found that the high energy metabolism status is positively correlated with the poor prognosis of patients with lung adenocarcinoma. We constructed a scoring system (mitoRiskscore) based on the gene expression of specific mitochondrial localized proteins through univariate and LASSO cox regression. It has been shown that high mitoRiskscore was correlated with a shorter survival time after surgery in patients with lung adenocarcinoma. Compared with the typical TNM grading system, the mitoRiskscore gene panel had higher prediction accuracy. A vast number of external verification results ensured its universality. Additionally, the mitoRiskscore could evaluate the metabolic pattern and chemotherapy sensitivity of the tumor samples. Lung adenocarcinoma with higher mitoRiskscore was more active in glycolysis, and oxidative phosphorylation expression of proliferation-related pathway genes was also significantly upregulated. In contrast, patients with low mitoRiskscore had similar metabolic patterns to normal tissues. In order to improve the accuracy of prediction ability and promote clinical usage, we developed a nomogram that combined mitoRiskscore and clinical prognostic factors to predict the 3-year, 5-year, and 10-year survival rates of patients. We also performed in vitro experiments to verify the function of the key genes in the mitoRiskscore panel. In conclusion, the mitoRiskscore scoring system may assist clinicians to judge the postoperative survival rate and chemotherapy of patients with lung adenocarcinoma.

Highlights

In recent decades, lung cancer is a common occurrence and the leading cause of cancer-related deaths
In order to explore the mitochondrial activity in lung cancer, we downloaded several mitochondrial-related pathways from molecular signature database (MSigDB), including the complete mito-protein genes, fatty acid metabolism, glycolytic pathways, hypoxia and high expression genes, and oxidative phosphorylation
It shows that lung cancer cells are not hypoxic, and fatty acid metabolism is not vigorous

Summary

Introduction

Lung cancer is a common occurrence and the leading cause of cancer-related deaths. The known factors related to the occurrence of LUAD include gender, age, smoking, environment, and heredity [2]. With the rise of medical technology, lung cancer treatment is gradually increasing, from simple surgical resection to surgery combined with adjuvant chemotherapy, immunotherapy, targeted drug therapy, and biological therapy [3]. We have made innovations in lung cancer treatment, LUAD’s annual mortality rate has not decreased as expected. It may be due to our lack of assessment of LUAD patients’ survival status after surgery [4]. If we can accurately predict patients’ survival rate after surgery and each patient’s treatment preference, clinicians can provide patients with accurate postoperative treatment. Patients with low predicted survival rates should be reviewed more frequently and treated with high-dose drugs; for patients with high predicted survival rates, more

Methods

Results

Conclusion