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. 2018 May;144(5):893-900.
doi: 10.1007/s00432-018-2619-3. Epub 2018 Mar 6.

Podoplanin-positive cancer-associated fibroblast recruitment within cancer stroma is associated with a higher number of single nucleotide variants in cancer cells in lung adenocarcinoma

Shoko Nakasone  1   2 , Sachiyo Mimaki  3 , Tomohiro Ichikawa  2 , Keiju Aokage  2 , Tomohiro Miyoshi  2 , Masato Sugano  4 , Motohiro Kojima  1 , Satoshi Fujii  1 , Takeshi Kuwata  4 , Atsushi Ochiai  5 , Masahiro Tsuboi  2 , Koichi Goto  6 , Katsuya Tsuchihara  3 , Genichiro Ishii  7
Affiliations

Podoplanin-positive cancer-associated fibroblast recruitment within cancer stroma is associated with a higher number of single nucleotide variants in cancer cells in lung adenocarcinoma

Shoko Nakasone et al. J Cancer Res Clin Oncol. 2018 May.

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.

Keywords: Cancer-associated fibroblasts; Lung adenocarcinoma; Podoplanin; Single nucleotide variants.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Podoplanin expression in cancer-associated fibroblasts (CAFs). a Podoplanin-positive CAFs cases. b Podoplanin-negative CAFs cases
Fig. 2
Fig. 2
Kaplan–Meier curve according to the expression status of podoplanin in the CAFs. a Kaplan–Meier curve for recurrence-free survival patients according to the expression status of podoplanin in the CAFs. b Kaplan–Meier curve for overall survival patients according to the expression status of podoplanin in the CAFs
Fig. 3
Fig. 3
The association between podoplanin expression in CAFs and number of single nucleotide variants (SNVs) in cancer cells. a All cases (n = 97). b Non-smoking cases (n = 43)
Fig. 4
Fig. 4
The percentage of each SNVs in podoplanin-positive and podoplanin-negative cases. a All cases (n = 97). b Non-smoking cases (n = 43)
See this image and copyright information in PMC

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References

    1. Alexandrov LB, Ju YS, Haase K et al (2016) Mutational signatures associated with tobacco smoking in human cancer. Science 354:618–622. 10.1126/science.aag0299 - PMC - PubMed
    1. Bavarva JH, Tae H, McIver L, Garner HR (2014) Nicotine and oxidative stress induced exomic variations are concordant and overrepresented in cancer-associated genes. Oncotarget 5:4788–4798. 10.18632/oncotarget.2033 - PMC - PubMed
    1. Bristow RG, Hill RP (2008) Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability. Nat Rev Cancer 8:180–192. 10.1038/nrc2344 - PubMed
    1. Collins MA, Bednar F, Zhang Y et al (2012) Oncogenic Kras is required for both the initiation and maintenance of pancreatic cancer in mice. J Clin Invest 122:639–653. 10.1172/JCI59227 - PMC - PubMed
    1. Dimanche-Boitrel MT, Vakaet L, Pujuguet P et al (1994) In vivo and in vitro invasiveness of a rat colon-cancer cell line maintaining E-cadherin expression: an enhancing role of tumor-associated myofibroblasts. Int J Cancer 56:512–521 - PubMed

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