Abstract
The only potentially curative treatment for lung adenocarcinoma patients remains complete resection of early-stage tumors. However, many patients develop recurrence and die of their disease despite curative surgery. Underlying mechanisms leading to establishment of systemic disease after complete resection are mostly unknown. We therefore aimed at identifying molecular signatures of resected lung adenocarcinomas associated with the risk of an early relapse. The study comprised 89 patients with totally resected stage IA–IIIA lung adenocarcinomas. Patients suffering from an early relapse within two years after surgery were compared to patients without a relapse in two years. Patients were clinically and molecular pathologically characterized. Tumor tissues were immunohistochemically analyzed for the expression of Ki67, CD45, CD4, CD8, PD1, PD-L1, PD-L2 and CD34, by Nanostring nCounter PanCancer Immune Profiling Panel as well as a comprehensive methylome profiling using the Infinium MethylationEPIC BeadChip. We detected differential DNA methylation patterns as well as significantly differentially expressed genes associated with an early relapse after complete resection. Especially, CD1A was identified as a potential biomarker, whose reduced expression is associated with an early relapse. These findings might help to develop biomarkers improving risk assessment and patient selection for adjuvant therapy as well as establish novel targeted therapeutic strategies.
Highlights
The only potentially curative treatment for lung adenocarcinoma patients remains complete resection of early-stage tumors
A lot of patients suffer from early post-surgical recurrence after complete resection of early-stage lung adenocarcinomas, whereas other patients present with quite long relapse-free survival
In a study on the prognostic relevance of angiogenesis in stage III Non-small cell lung cancer (NSCLC) by Kreuter et al microvessel density was a prognostic factor in the subgroup of R0-resected stage IIIA NSCLC patients[14]
Summary
The only potentially curative treatment for lung adenocarcinoma patients remains complete resection of early-stage tumors. We aimed at identifying molecular signatures of resected lung adenocarcinomas associated with the risk of an early relapse. CD1A was identified as a potential biomarker, whose reduced expression is associated with an early relapse These findings might help to develop biomarkers improving risk assessment and patient selection for adjuvant therapy as well as establish novel targeted therapeutic strategies. Underlying mechanisms that lead to establishment of systemic spread of disease after complete resection are mostly unknown and the current staging system fails to appropriately predict clinical outcome in individual patients[3]. Category Stage IA Stage IB Stage IIA Stage IIB Stage IIIA V0: without vascular invasion V1: with vascular invasion VX: vascular invasion not determined L0: without lymphatic invasion L1: with lymphatic invasion LX: lymphatic invasion not determined G1: well differentiated (Low grade) G2: moderately differentiated (Intermediate grade) G3: poorly differentiated (High grade) G4: undifferentiated (High grade) GX: G status not determined Age [years]: average Age [years]: standard deviation Age [years]: median Sex: male Sex: female Nicotine: yes Nicotine: no Packyears: average Packyears: standard deviation Packyears: median Vital status: alive Vital status: dead Survival [months]: average Survival [months]: standard deviation Survival [months]: median Time to relapse [months]: average Time to relapse [months]: standard deviation Time to relapse [months]: median a certain amount of risk and an accurate selection of those patients who are eligible for complete resection needs to be a chieved[4]
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