Abstract
Purpose
Podoplanin-positive cancer-associated fibroblasts (CAFs) play an essential role in tumor progression. However, it is still unclear whether specific genomic alterations of cancer cells are required to recruit podoplanin-positive CAFs. The aim of this study was to investigate the relationship between the mutation status of lung adenocarcinoma cells and the presence of podoplanin-positive CAFs.
Methods
Ninety-seven lung adenocarcinomas for which whole exome sequencing data were available were enrolled. First, we analyzed the clinicopathological features of the cases, and then, evaluated the relationship between genetic features of cancer cells (major driver mutations and the number of single nucleotide variants, SNVs) and the presence of podoplanin-positive CAFs.
Results
The presence of podoplanin-positive CAFs was associated with smoking history, solid predominant subtype, and lymph node metastasis. We could not find any significant correlations between major genetic mutations (EGFR, KRAS, TP53, MET, ERBB2, BRAF, and PIC3CA) in cancer cells and the presence of podoplanin-positive CAFs. However, cases with podoplanin-positive CAFs had a significantly higher number of SNVs in cancer cells than the podoplanin-negative CAFs cases (median 84 vs 37, respectively; p = 0.001). This was also detected in a non-smoker subgroup (p = 0.037). Multivariate analyses revealed that the number of SNVs in cancer cells was the only statistically significant independent predictor for the presence of podoplanin-positive CAFs (p = 0.044).
Conclusions
In lung adenocarcinoma, the presence of podoplanin-positive CAFs was associated with higher numbers of SNVs in cancer cells, suggesting a relationship between accumulations of SNVs in cancer cells and the generation of a tumor-promoting microenvironment.
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2H9Oa0r
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