Abstract
The identification of reliable indicators in the tumor microenvironment (TME) is critical for tumor prognosis. Tumor associated macrophages (TAMs) are the major component of non-tumor stromal cells in TME and have increasingly been recognized as a predictive biomarker for lung adenocarcinoma (LUAD) prognosis. Here, we report the development of a prognosis model for LUAD using three immune-related genes (IRGs) detected in The Cancer Genome Atlas (TCGA) which potentially regulate TAMs in TME. In 497 LUAD patients, higher immune scores conferred better overall survival (OS). We identified 93 hub IRGs out of 234 for further prognostic significance. Among them, three IRGs (BTK, Cd1c, and S100P) were proved to be closely correlated to the prognosis of patients with LUAD. Moreover, the immune risk score (IRS) based on the gene expression level of the three IRGs was an independent prognostic factor for OS. Higher IRS predicted lower OS, higher mortality and worse tumor stage. With a good predictive ability [area under the ROC curve (AUC) in TCGA = 0.701, AUC in GEO = 0.722], the IRS contributed to a good risk stratification ability of the nomogram. Immunologically, the three IRGs were related to M1 macrophages and NK cell subsets in TME. Interestingly, by characterizing these immune components in situ we found that S100P is a driver for tumor cells to induce TAM migration and M2 polarization in the immunosuppressive tumor niche. We identified the key genes driving TAM migration and transformation and elucidated the immune landscape of LUAD. The data suggest that IRGs from TME have the potential to become indicators for estimating cancer prognosis and guiding individualized treatment.
Highlights
Lung adenocarcinoma (LUAD) is one of the leading causes of cancer-related deaths globally due to early metastasis and poor prognosis (Skoulidis et al, 2018)
To further verify the relationship between S100P and macrophage polarization, we designed a loss of function assay by transfecting
The immune status of tumor microenvironment (TME) is closely related to the prognosis of lung adenocarcinoma (LUAD) patients
Summary
Lung adenocarcinoma (LUAD) is one of the leading causes of cancer-related deaths globally due to early metastasis and poor prognosis (Skoulidis et al, 2018). Immunosuppressive cells in the tumor microenvironment (TME) facilitate tumor metastasis and tumor stem cell formation, which are closely related to clinically poor prognosis (Li et al, 2019). Single cell sequencing is well suited to identify diverse immune cell subsets in TME, it costs too much for routine diagnostic and prognostic evaluation of LUAD patients (Guo et al, 2020). It is necessary to identify crucial IRGs closely related to immune cell dysfunction for an economically acceptable and reliable prognostic prediction. A network analysis integrating the immune gene signature and cell map is important to illuminate the mechanism of TME development, which could improve the accuracy of prognosis prediction
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