Landscape of Mitochondria Genome and Clinical Outcomes in Stage 1 Lung Adenocarcinoma.

Lovely Raghav,Shinn-Ying Ho,Kuo-Hsuan Hsu,Jeremy J.W Chen,Sung-Liang Yu,Chih Liang Wang ,Yi Chiung Hsu ,Pan Chyr Yang ,Chih Yi Chen ,Ker Chau Li ,Yu Cheng Li ,Gee Chen Chang ,Shin Sheng Yuan ,Tsung Ying Yang ,Jeng‐Sen Tseng ,Hsuan-Shu Lee ,Shih Bin Su ,Yun‐Chien Chang ,Chun‐Yi Chuang ,Huei‐Wen Chen ,Kun Chieh Chen ,Hsuan Yu Chen

doi:10.3390/cancers12030755

Abstract

Risk factors including genetic effects are still being investigated in lung adenocarcinoma (LUAD). Mitochondria play an important role in controlling imperative cellular parameters, and anomalies in mitochondrial function might be crucial for cancer development. The mitochondrial genomic aberrations found in lung adenocarcinoma and their associations with cancer development and progression are not yet clearly characterized. Here, we identified a spectrum of mitochondrial genome mutations in early-stage lung adenocarcinoma and explored their association with prognosis and clinical outcomes. Next-generation sequencing was used to reveal the mitochondrial genomes of tumor and conditionally normal adjacent tissues from 61 Stage 1 LUADs. Mitochondrial somatic mutations and clinical outcomes including relapse-free survival (RFS) were analyzed. Patients with somatic mutations in the D-loop region had longer RFS (adjusted hazard ratio, adjHR = 0.18, p = 0.027), whereas somatic mutations in mitochondrial Complex IV and Complex V genes were associated with shorter RFS (adjHR = 3.69, p = 0.012, and adjHR = 6.63, p = 0.002, respectively). The risk scores derived from mitochondrial somatic mutations were predictive of RFS (adjHR = 9.10, 95%CI: 2.93–28.32, p < 0.001). Our findings demonstrated the vulnerability of the mitochondrial genome to mutations and the potential prediction ability of somatic mutations. This research may contribute to improving molecular guidance for patient treatment in precision medicine.

Highlights

Lung cancer is the leading cause of cancer death worldwide
We examined the associations of somatic mutations with prognosis of lung adenocarcinoma (LUAD) for individual genes, complexes, and the D-loop region
Mitochondrial mutations and/or dysfunction play a crucial role in shifting cellular metabolism to a state more favorable for cancer proliferation [26,27]

Summary

Introduction

Lung cancer is the leading cause of cancer death worldwide. Despite the advances in early detection and therapeutic methods, the 5 year survival rate for early-stage lung cancer remains about 55% [1]. Genomic aberrations associated with lung cancer development have been studied systematically in recent years [2]. Driver mutations in EGFR, ALK, and ROS1 have been identified for non-smoking-associated LUAD [3]. EGFR-activating mutations are frequently observed in East. Female, and non-smoking LUAD patients [4,5]. For early-stage patients, surgery with or without adjuvant chemotherapy remains the therapeutic gold standard [6]. About 30–50% of early-stage patients develop disease relapse within 5 years of surgery, and identification of prognostic markers for risk of relapse remains a challenge [6]

Methods

Results

Discussion

Conclusion