Transcriptome of non-involved lung parenchyma from smoker lung adenocarcinoma patients from Milan, Italy.. Homo sapiens

Scientific evidence indicates that genetic factors may contribute to differences in lung cancer risk for individuals with similar levels of tobacco exposure, which is the main environmental risk factor of lung cancer. Moreover, lung cancer patients show large differences in clinical staging and survival; these differences seem to be attributable, at least partially, to the genetic background. The analysis of the molecular properties (e.g., germline variations and genome-wide expression levels) of non-involved tissue from lung cancer patients may contribute in the identification of genetic factors involved in the development and progression of this pathology. To this aim, we analyzed two series (discovery series, n = 204, and validation series, n = 78) of non-tumor lung tissue samples from smokers that underwent surgical lobectomy for adenocarcinoma in Milan, Italy. First, we examined the whole transcriptome of these two series to define the candidate genes and pathways associated with either lung cancer risk or prognosis in this cohort. Moreover, as sex and age are known to strongly influence the pathophysiology of human lungs, we used transcriptome data from the same samples to identify sex- and age-related transcriptional differences in lung. Overall design: Samples of non-involved (apparently normal) lung parenchyma excised from patients who underwent lobectomy for lung adenocarcinoma in the area around Milan, Italy. The samples were analyzed in two sets: a discovery series (n = 204) and a validation series (n = 78).

科学研究证据表明，在烟草暴露水平相近的人群中，遗传因素可能是导致肺癌风险差异的重要因素——而烟草暴露正是肺癌最主要的环境风险因素。此外，肺癌患者的临床分期与生存结局存在显著差异，这类差异至少在一定程度上可归因于个体的遗传背景。对肺癌患者非受累肺组织的分子特征（例如生殖系变异（germline variations）、全基因组表达水平（genome-wide expression levels））进行分析，有助于识别与该疾病发生、发展相关的遗传因素。基于此研究目标，我们对意大利米兰地区接受肺腺癌（adenocarcinoma）肺叶切除术（surgical lobectomy）的吸烟者的非肿瘤肺组织样本进行了分析，样本分为两个队列：发现队列（discovery series，n=204）与验证队列（validation series，n=78）。首先，我们对这两个队列的全转录组（transcriptome）进行检测，以明确本队列中与肺癌风险或预后相关的候选基因及信号通路（pathways）。此外，已知性别与年龄会显著影响人类肺部的病理生理学特征，因此我们利用同批次样本的转录组数据，识别肺部中与性别、年龄相关的转录组差异。整体实验设计：采集意大利米兰周边地区接受肺腺癌肺叶切除术患者的非受累（外观正常）肺实质组织样本，将其分为两组进行分析：发现队列（n=204）与验证队列（n=78）。