Tumor Immune Microenvironment Characterization of Primary Lung Adenocarcinoma and Lymph Node Metastases

Abstract

Background. The essential roles of the tumor microenvironment (TME) have been recognized during the initiation and progression of primary lung adenocarcinoma (LUAD). The aim of the present study was to delineate the immune landscape in both primary cancer and matched lymph node metastasis from a cohort of locally advanced stage LUAD patients with distinct outcomes. Methods. Formalin-fixed, paraffin-embedded samples were collected from 36 locally advanced LUAD patients. Transcriptome data of the tumor immune microenvironment were resolved using an immune oncology panel RNA sequencing platform. Bioinformatics approaches were used to determine the differentially expressed genes (DEGs), dysregulated pathways, and immune cell fraction between patients with early recurrence (ER) and late recurrence (LR). Results. Here, we showed that in primary cancer tissues, 23 DEGs were obtained between patients with ER and LR. Functional analysis revealed that the LR in LUAD patients may be associated with enriched gene sets belonging to the antigen presentation and MHC protein complex, innate immune response, and IFN-γ signaling pathways. Next, the transcriptome data were adopted to quantify immune cell fractions, indicating that high infiltration of mast cells and neutrophils was correlated with ER. Interestingly, similar findings were observed in metastatic lymph nodes from patients suffering from ER or LR. By analyzing the shared immune features of primary cancers and lymphatic metastases, we unraveled the prognostic value and joint utility of two DEGs, CORO1A and S100A8. Conclusions. In LUAD, the enrichment in antigen presentation, MHC protein complex, and IFN-γ signaling, and low infiltration of neutrophils in primary or metastatic nodules may be indications for a favorable prognosis. Integrated with bioinformatics approaches, transcriptome data of immune-related genes from formalin-fixed, paraffin-embedded (FFPE) samples can effectively profile the landscape of the tumor immune microenvironment and help predict clinical outcomes.

Uncovering the relationship between YTHDF1 related to immune cells and prognosis and diagnosis in lung adenocarcinoma

“…The changes of TIME play a signi cant role in the progression of LUAD (51,52). YTHDF1, as a m6A modi cation regulator gene, plays a signi cant role in immune regulation of various cancers (53)(54)(55).…”

Expression Landscape and Functional Roles of HOXA4 and HOXA5 in Lung Adenocarcinoma

“…Due to no obvious symptoms and lack of effective screening tests, most LUAD Ivyspring International Publisher patients were judged to be in late clinical stage when diagnosed, and missed the window for best opportunity of surgical treatment [1]. Although multidisciplinary efforts jointly have greatly promoted the advancement of diagnosis and treatment of LUAD and even target gene therapy have been proposed, the prognosis of LUAD patients remained poor and some patients were tortured by short-term relapse or distant metastasis [2][3][4][5]. Thus, it was necessary to investigate genes related to the occurrence and progression of LUAD and find new biomarkers for early diagnosis and clinical treatment of LUAD.…”