Transcriptional Characterization Of The Tumor Immune Microenvironment And Its Prognostic Value For Locally Advanced Lung Adenocarcinoma In A Chinese Population

Abstract

Objective

We investigated the relationship of the transcriptional tumor immune microenvironment with prognosis of patients with locally advanced lung adenocarcinoma (LUAD).

Materials and methods

A targeted RNA-Seq approach was used to measure the abundance of 395 immune-related transcripts of 24 formalin-fixed paraffin embedded (FFPE) tumor specimens from our institution and transcription data of 85 matched LUAD samples from The Cancer Genome Atlas (TCGA). Gene set variation analysis (GSVA) was used to identify gene sets related to prognosis, and the microenvironment cell-population (MCP)-counter method was used to quantify infiltrated immune cells. Survival analysis with the log rank test was used to determine the relationships of different immune-related transcripts with prognosis. Cox proportional hazards models were also used to identify risk factors associated with poor prognosis.

Results

Among our patients, GSVA and the log rank test demonstrated that enrichment of the antigen processing pathway (P = 0.01) correlated with a favorable prognosis. MCP-counter and survival analysis demonstrated that greater CD8 T cell infiltration correlated with a favorable prognosis (P = 0.05), but greater infiltration of neutrophils (P = 0.014) and NK cells (P = 0.015) correlated with poor prognoses. Cox hazard analysis showed that greater infiltration of neutrophils was an independent risk factor for poor prognosis. These results were consistent with LUAD data from TCGA.

Conclusion

When integrated with computational bioinformatics methods, targeted RNA-Seq from FFPE specimens provides profiles of the tumor immune microenvironment that have prognostic value for patients with locally advanced LUAD.

Keywords:

• NSCLC
• lung adenocarcinoma
• RNA-Seq
• tumor immune microenvironment
• transcriptomic markers

Acknowledgments

The present study was funded by the Human Provincial Science and Technology Department (2017JJ2345) and the National Natural Science Foundation of China (No. 81673516).

Ethical Approval

This study has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Disclosure

The authors report no conflicts of interest in this work.