Clinical impact of the lung tissue transcriptome in a teenager with multifocal invasive mucinous adenocarcinoma-a case report

The transcriptional profiling of cancer and normal tissues harboring cancer can be a clinical and discovery tool, especially for the study of rare tumors. Invasive mucinous adenocarcinoma (IMA) is a rare lung cancer histotype, which mostly affects the elderly and commonly has a poor prognosis. We investigated the exceptional case of a teenager, exposed to passive smoke and chemical carcinogens, who developed a multifocal IMA with bilateral involvement. The malignancy was asymptomatic and was diagnosed occasionally during hospitalization for acute abdominal pain due to adnexitis. The young patient underwent video-assisted thoracoscopic surgery and lung samples were analysed by RNA-Sequencing. The transcriptome of patient’s normal and neoplastic lung tissues was compared with matched healthy controls and IMA signature cases, using Gene Set Enrichment Analyses, Gene Ontology and Genotype Tissue Expression database. Compared to healthy controls, the patient’s lung tissue lacked the expression of lymphocyte and humoral-mediated immune response genes, whereas genes driving the response to stimulus, chemical and organic substances, primarily, CXCL8, ACKR1, RAB7B, HOXC9, HOXD9, KLF5 and NKX2-8 were overexpressed. Genes driving extracellular structure organization, cell adhesion, cell movement, metabolic and apoptotic processes were down-modulated in patient’s lung tissue. When compared to IMA signature cases, the patient’s IMA revealed a prevalent expression of genes regulating the response to stimulus, myeloid and neutrophil activation and immune system processes, primarily CD1a and CXCL13/ BCA1, whereas stemness genes and proto-oncogenes, such as SOX4, HES1, IER3 and SERPINH1 were downmodulated. These transcriptional signature associated with a favorable clinical course, since the patient was healthy five years after initial diagnosis. The transcriptome of the normal tissues bearing tumor provides meaningful information on the gene pathways driving tumor histogenesis, with a prospective impact on early diagnosis. Unlike the tumor histotype-related transcriptional signature, the individual patient’s signature enables tailored treatment and accurate prognosis.