Erasmus University Medical Center, Departments of Pulmonary Diseases, Internal Medicine and Pathology, Bioinformatic Unit, Dr. Molewaterplein 40, 3015 GD, the Netherlands.
University of Groningen and University Medical Center Groningen, Departments of Pulmonary Diseases and Pathology and Medical Biology, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
Lung Cancer. 2020 Aug;146:341-349. doi: 10.1016/j.lungcan.2020.06.008. Epub 2020 Jun 20.
Non-small-cell lung cancer exhibits a range of transcriptional and epigenetic patterns that not only define distinct phenotypes, but may also govern immune related genes, which have a major impact on survival.
We used open-source RNA expression and DNA methylation data of the Cancer Genome Atlas with matched non-cancerous tissue to evaluate whether these pretreatment molecular patterns also influenced genes related to the immune system and overall survival.
The distinction between lung adenocarcinoma and squamous cell carcinoma are determined by 1083 conserved methylation loci and RNA expression of 203 genes which differ for >80 % of patients between the two subtypes. Using the RNA expression profiles of 6 genes, more than 95 % of patients could be correctly classified as having either adeno or squamous cell lung cancer. Comparing tumor tissue with matched normal tissue, no differences in RNA expression were found for costimulatory and co-inhibitory genes, nor genes involved in cytokine release. However, genes involved in antigen presentation had a lower expression and a wider distribution in tumor tissue.
Only a small number of genes, influenced by DNA methylation, determine the lung cancer subtype. The antigen presentation of cancer cells is dysfunctional, while other T cell immune functions appear to remain intact.
非小细胞肺癌表现出一系列转录和表观遗传模式，这些模式不仅定义了不同的表型，而且可能还控制着与免疫相关的基因，这些基因对生存有重大影响。
我们使用癌症基因组图谱的开源 RNA 表达和 DNA 甲基化数据，并结合配对的非癌组织，评估这些预处理分子模式是否也会影响与免疫系统和整体生存相关的基因。
肺腺癌和鳞状细胞癌的区别由 1083 个保守的甲基化位点和 203 个基因的 RNA 表达决定，这两个亚型之间超过 80%的患者存在差异。使用 6 个基因的 RNA 表达谱，超过 95%的患者可以正确分类为患有腺癌或鳞状细胞肺癌。与配对的正常组织相比，在共刺激和共抑制基因以及细胞因子释放相关基因中没有发现 RNA 表达的差异。然而，参与抗原呈递的基因在肿瘤组织中的表达较低且分布较广。
只有少数受 DNA 甲基化影响的基因决定了肺癌的亚型。癌细胞的抗原呈递功能失调，而其他 T 细胞免疫功能似乎保持完整。
