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bioRxiv · 10.1101/677567

Novel immune and stromal subtype classification system of lung adenocarcinoma based on tumor microenvironment

Zeng, Z.·Li, J.·Zhang, N.·Jiang, X.·Gao, Y.·Xu, L.·Liu, X.·Chen, J.·Han, L.·Ren, J.·Gong, Y.·Xie, C.
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Abstract

BackgroundTumor microenvironment has complex effects on tumorigenesis and metastasis in lung adenocarcinoma (LUAD). However, there is still a lack of comprehensive understanding of the relationship between immune and non-immune stromal characteristics in tumor microenvironment.\n\nPatients and methodsEight cohort of 1681 lung caner patients were included in this study. The immune and non-immune stromal signatures of tumor microenvironment were identified by eigendecomposition and extraction algorithms. We developed a novel immune and stromal scoring system to quantify anti-tumor immune and promote-metastasis stromal activation, namely PMBT (prognostic model based on tumor microenvironment) as an R package. Tumors were classified into 4 subtypes according to PMBT system. Comprehensive analysis was performed in different subtypes.\n\nResultsThe 4 subgroups had different mutation landscape, molecular, cellular characteristics and prognosis, which validated by 7 data sets containing 1175 patients. 19% patients was characterized by highly active anti-tumor reaction with high production of immunoactive mediators, immunocyte, low fibroblasts infiltration, low TGF-{beta}, VEGFA, collagen and glucose catabolic, low immune checkpoint per T cell, tumor mutation burden, and favourable overall survival (all, P < 0.05) named high-immune and low-stromal activation subgroup (HL). Cellular paracrine network showed both high humoral and cellular immune interaction in HL group. The low-immune and high-stromal activation group (19%) had opposite characteristics with HL group. Moreover, the PMBT system showed the value to predict overall survival and immunotherapy responses (all, P < 0.05).\n\nConclusionsDifferent molecular, cellular characteristics, mutation landscape and prognosis were discovered in the 4 subgroups. Our classification, PMBT system provided novel insight for clinical monitoring and treatment in LUAD.

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Zeng, Z., Li, J., Zhang, N., Jiang, X., Gao, Y., Xu, L., Liu, X., Chen, J., Han, L., Ren, J., Gong, Y., Xie, C.. 2019-06-21. Novel immune and stromal subtype classification system of lung adenocarcinoma based on tumor microenvironment. https://doi.org/10.1101/677567

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