Abstract
The malignant phenotypes of cancer are defined not only by its intrinsic tumor cells but also by the tumor infiltrating immune cells (TIICs) recruited to the cancer microenvironment. Clear cell renal cell carcinoma (ccRCC) immune microenvironment plays an important role in the tumorigenesis. This research investigated the characteristics of immune cell invasion of renal cell carcinoma and provided clues for future clinical implementation. Retrospectively, ccRCC gene expression was analyzed with appropriate clinicopathological data from the Cancer Genome Atlas (TCGA) and GEO database up to December 2019. The CIBERSORT algorithm, meta-analysis, principal component analysis (PCA), Single-Sample Gene Set Enrichment Analysis (ssGSEA) and hierarchical agglomerative clustering were used to measure and evaluate the respective proportions of 22 cell types of immune infiltration using normalized gene expression data. We also focused on evaluating the association with TIICs subpopulations and clinical features and molecular subtypes. TIICs subpopulation, especially Macrophages subgroup, T follicular helper (Tfh) cells and CD8 T cells, all contribute to tumorigenesis. Unsupervised clustering analysis revealed that there existed two distinct TIICs subgroups with different survival patterns. TIICs are extensively involved in the pathogenesis and development of the ccRCC. Characterizing the composition of TIICs influences the metabolism of tumors, activity, level, stage, and survival of patients. Collectively, the TIIC analysis has the potential to assist in the assessment and selection of ccRCC prognosis and treatment.
Highlights
Clear cell renal cell carcinoma is the second most common tumor in urology
Immunohistochemical (IHC) stainings showed that the expression trends of different levels of specific immune cells (Figure 2D)
In increments of 10%, we randomly deleted this gene group until 10% of the genes remained. These findings suggested that the accuracy of the inferred immune cell proportions was accurate while variable limited to cases with CIBERSORT P ≤ 0.05 and barcode genes >0%
Summary
Clear cell renal cell carcinoma (ccRCC) is the second most common tumor in urology. As one of the popular urinary tumors, the incidence rate increases by 2–4% per year [1]. Surgery is the most important treatment method for most patients with RCC and has achieved good efficacy in early renal cancer patients. Recurrence and metastasis are the main factors influencing the survival of ccRCC patients. The prognosis varied among ccRCC patients with the same TNM stage due to the heterogeneous subgroup of cancer cells.
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