Molecular characteristics of lung adenocarcinoma with respect to patient age at diagnosis

Abstract

Lung cancer is primarily a disease of the elderly, with a median age at diagnosis around 70 years. In our study we sought to address the question of whether and how clinical characteristics, molecular alterations and molecular phenotypes differ between patient populations with early-stage lung adenocarcinoma (AC) with respect to age at diagnosis. Patients were stratified based on age at diagnosis into five systematic age bins (<50, 50-60, 60-70, 70-80 and ≥80 years). To assess clinicopathological variables on a population-based level, we accessed data from the national quality registry for lung cancer in Sweden. In parallel, we used compiled datasets from public cohorts to investigate focal and genome-wide DNA alterations, epigenetic alterations, immune composition and transcriptional patterns in relation to age at diagnosis. Gender, stage, WHO performance and likelihood of receiving chemotherapy as adjuvant treatment were linked to age at diagnosis. Associations between younger patient age and likelihood of harboring certain driver mutations (eg, in EGFR and ALK) were confirmed. We also found an association between age at diagnosis and certain mutational signatures. However, age did not seem to drive transcriptional, copy number, or epigenetic variation in the tumors. Based on our findings, age at diagnosis alone does not appear to provide an additional layer of biological complexity above that of proposed genetic and transcriptional phenotypes of AC.

Aging-associated Alterations in the Gene Regulatory Network Landscape Associate with Risk, Prognosis and Response to Therapy in Lung Adenocarcinoma

“…We suspect that a higher targeting of immune pathways in conjunction with a higher proportion of immune cells among older individuals might contribute to an age-biased response to immunotherapy. This is concordant with evidence from earlier studies which demonstrated that while chemotherapy is more beneficial for younger individuals [5], some immune checkpoint inhibitors provide greater benefit to adults with age 65 or older, compared to younger adults [54,55].…”

“…While lung adenocarcinoma (LUAD) in younger adults is often diagnosed at more advanced stages compared to those in older adults [3], elderly individuals have more comorbidities and tend to be less tolerant of certain cancer therapeutics than younger individuals [4]. These differences are likely the result of aging-induced alterations in the regulation of key cellular processes [5], but the mechanism by which age shifts the gene regulatory landscape to alter lung cancer risk and survival outcome is largely unknown. In this paper we address this critical gap in our understanding by building individual (person)-specific gene regulatory networks to gain insights into aging related changes in gene regulation that might influence the risk and prognosis of LUAD across all age groups.…”

Distinguishing EGFR mutant subtypes in stage IA non-small cell lung cancer using the presence status of ground glass opacity and final histologic classification: a systematic review and meta-analysis

“…Multiple studies have shown that the risk of EGFR mutations increases with age in NSCLC patients ( 31 , 32 ). Despite adjusting for patient histology, smoking status, and pathological staging, one study found an independent statistical difference between EGFR mutations and the age of the patient at diagnosis ( 33 ). In response to this conclusion, we suggest that those who are older have an increased risk of developing mutations due to changes in their own hormone levels, diminished nucleotide repair capacity, and increased exposure to carcinogenic stimuli from the environment ( 34 – 37 ).…”