Papillary thyroid carcinoma behavior: clues in the tumor microenvironment

Abstract

The prevalence of thyroid carcinoma is increasing and represents the most common endocrine malignancy, with papillary thyroid carcinoma (PTC) being the most frequent subtype. The genetic alterations identified in PTCs fail to distinguish tumors with different clinical behaviors, such as extra-thyroidal extension and lymph node metastasis. We hypothesize that the immune microenvironment may play a critical role in tumor invasion and metastasis. Computational immunogenomic analysis was performed on 568 PTC samples in The Cancer Genome Atlas using CIBERSORT, TIMER and TIDE deconvolution analytic tools for characterizing immune cell composition. Immune cell infiltrates were correlated with histologic type, mutational type, tumor pathologic T stage and lymph node N stage. Dendritic cells (DCs) are highly associated with more locally advanced tumor T stage (T3/T4, odds ratio (OR) = 2.6, CI = 1.4–4.5, P = 5.4 × 10−4). Increased dendritic cells (OR = 3.4, CI = 1.9–6.3, P = 5.5 × 10−5) and neutrophils (OR = 10.5, CI = 2.7–44, P = 8.7 × 10−4) significantly correlate with lymph node metastasis. In addition, dendritic cells positively correlate with tall cell morphology (OR = 4.5, CI = 1.6–13, P = 4.9 × 10−3) and neutrophils negatively correlate with follicular morphology (OR = 1.3 × 10−3, CI = 5.3 × 10−5–0.031, P = 4.1 × 10−5). TIDE analysis indicates an immune-exclusive phenotype that may be mediated by increased galectin-3 found in PTCs. Thus, characterization of the PTC immune microenvironment using three computational platforms shows that specific immune cells correlate with mutational type, histologic type, local tumor extent and lymph node metastasis. Immunologic evaluation of PTCs may provide a better indication of biologic behavior, resulting in the improved diagnosis and treatment of thyroid cancer.

Immune-related key gene CLDN10 correlates with lymph node metastasis but predicts favorable prognosis in papillary thyroid carcinoma

“…In colon cancer, low tumor purity is correlated with poor prognosis because of high mutation frequency in key pathways and purity-related microenvironmental changes [9]. In PTC, immune cell infiltrates are correlated with lymph node N stage [10]. In these biological processes, immune-related genes may influence the prognosis of cancer patients by affecting the abundance of infiltrating immune cells [11].…”

Identifying the Transcriptional Regulatory Network Associated With Extrathyroidal Extension in Papillary Thyroid Carcinoma by Comprehensive Bioinformatics Analysis

“…In the brown module, GO analysis suggested functions related to the immune response. Immune cells are an important component of the tumor stroma and immunemediated dysregulation has been associated with many cancers (Balkwill et al, 2005;de Visser et al, 2006;Wyckoff et al, 2007;Bergdorf et al, 2019). Consistently, KEGG pathway analysis also suggested immunoregulatory functions, as well as enrichment in cancer-associated pathways.…”

The multifaceted anti-cancer effects of BRAF-inhibitors

“…Evidence that BRAF inhibitors do play a role in determining the specific composition of the tumor microenvironment was also provided by translational studies [77]. These studies were mostly performed on biopsy samples derived from human melanomas.…”