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. 2017 Dec;14(6):7931-7940.
doi: 10.3892/ol.2017.7195. Epub 2017 Oct 16.

Peripheral lung adenocarcinomas harboring epithelial growth factor receptor mutations with microRNA-135b overexpression are more likely to invade visceral pleura

Hanbo Le  1 , Xiaoling Wang  2 , Yao Zha  2 , Jie Wang  2 , Wangyu Zhu  2 , Zhinan Ye  2 , Xiaoguang Liu  2 , Haijie Ma  2 , Yongkui Zhang  1
Affiliations

Peripheral lung adenocarcinomas harboring epithelial growth factor receptor mutations with microRNA-135b overexpression are more likely to invade visceral pleura

Hanbo Le et al. Oncol Lett. 2017 Dec.

Abstract

Lung adenocarcinoma, characterized by its early and aggressive local invasion and high metastatic potential, is the most frequently observed histological type of non-small-cell lung cancer (NSCLC). Visceral pleural invasion (VPI) caused by peripheral lung adenocarcinomas is closely associated with the poor prognosis of patients with NSCLC. The association between VPI and some clinicopathological characteristics has been observed in the past few decades. However, the molecular mechanism of VPI in lung adenocarcinomas is unknown. In the present, the expression level of microRNA (miR-)135b and epidermal growth factor receptor (EGFR) mutations using the reverse transcription-quantitative polymerase chain reaction and DNA sequencing, respectively. In addition, the present study aimed at exploring the association between the miR-135b level, EGFR mutations and VPI in peripheral lung adenocarcinoma. The results of the present study demonstrated that miR-135b was significantly upregulated in lung adenocarcinoma compared with adjacent normal tissue and positively associated EGFR mutations in peripheral lung adenocarcinoma. Furthermore, it was identified that lung adenocarcinomas with EGFR mutations and miR-135b overexpression were more likely to invade visceral pleura. Taken together, these findings indicate that miR-135b overexpression is positively associated with mutations to EGFR, which may promote the development of peripheral lung adenocarcinomas by the formation of VPI. This indicates that the two factors may serve as prognostic markers and molecular targets for the treatment of peripheral lung adenocarcinomas.

Keywords: epithelial growth factor receptor mutations; invasion; microRNA-135b; peripheral lung adenocarcinomas; visceral pleural invasion.

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Figures

Figure 1.
Figure 1.
Expression level of miR-135b in 65 paraffin-embedded samples. (A) miR-135b is significantly upregulated in lung adenocarcinomas compared with the corresponding para-carcinoma tissue (P<0.001). (B) miR-135b is markedly upregulated in invasive lung adenocarcinoma compared to AIS/MIA (P=0.006). miR-135b, microRNA-135b; AIS/MIA, adenocarcinoma in situ/minimally invasive adenocarcinoma; IAC, invasive adenocarcinoma; ADC, adenocarcinoma; T, lung adenocarcinoma tissue; N, adjacent normal tissue.
Figure 2.
Figure 2.
EGFR mutation status in peripheral lung adenocarcinomas. (A) The EGFR mutation rate in invasive lung adenocarcinoma (60%) was higher than that in AIS/MIA (20%) (P=0.001). (B) Patients harboring EGFR mutations have a higher incidence of VPI (52.2%) than those with wild-type EGFR (11.9%) (P=0.000412). EGFR wt, patients with wild-type epithelial growth factor receptor; EGFR mt, patients harboring EGFR mutations; VPI, visceral pleural invasion; IAC, invasive adenocarcinoma.
Figure 3.
Figure 3.
Association between EGFR mutations, miR-135b and VPI. (A) Patients harboring EGFR mutations have exhibited higher expression levels of miR-135b than ones with wild-type EGFR. (P=0.025). (B) Patients harboring EGFR mutations with microRNA-135b overexpression are more likely to invade visceral pleura (P=0.000086). A total of 60% of patients harboring EGFR mutation with miR-135b overexpression had pleural invasion vs. 11% of patients that did not. EGFR wt, patients with wild-type epithelial growth factor receptor; EGFR mt, patients harboring EGFR mutations; ADC, adenocarcinoma; mir-135b, microRNA-135b; VPI, visceral pleural invasion.
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References

    1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30. doi: 10.3322/caac.21166. - DOI - PubMed
    1. Meoni G, Cecere FL, Lucherini E, Di Costanzo F. Medical treatment of advanced non-small cell lung cancer in elderly patients: A review of the role of chemotherapy and targeted agents. J Geriatr Oncol. 2013;4:282–290. doi: 10.1016/j.jgo.2013.04.005. - DOI - PubMed
    1. Lin CW, Chang YL, Chang YC, Lin JC, Chen CC, Pan SH, Wu CT, Chen HY, Yang SC, Hong TM, Yang PC. MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the hippo pathway and LZTS1. Nat Commun. 2013;4:1877. doi: 10.1038/ncomms2876. - DOI - PubMed
    1. Travis WD, Brambilla E, Riely GJ. New pathologic classification of lung cancer: Relevance for clinical practice and clinical trials. J Clin Oncol. 2013;31:992–1001. doi: 10.1200/JCO.2012.46.9270. - DOI - PubMed
    1. Siegelin MD, Borczuk AC. Epidermal growth factor receptor mutations in lung adenocarcinoma. Lab Invest. 2014;94:129–137. doi: 10.1038/labinvest.2013.147. - DOI - PubMed