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Clinical and Translational Oncology

, Volume 21, Issue 2, pp 197–205 | Cite as

Differential molecular markers of primary lung tumors and metastatic sites indicate different possible treatment selections in patients with metastatic lung adenocarcinoma

  • L.-L. Deng
  • H.-B. Deng
  • C.-L. Lu
  • G. Gao
  • F. Wang
  • Y. YangEmail author
Research Article
  • 56 Downloads

Abstract

Purpose

Detecting different molecular markers in primary tumors and metastases may provide therapeutic information. Here we investigated differences between primary tumors and four metastatic sites of lung adenocarcinoma in the biomarkers’ features and discussed potential therapeutic implications.

Methods

A total of 228 patients with metastatic lung adenocarcinoma were analyzed for EGFR, KRAS, BRAF and PIK3CA mutations detected by xTAG liquidchip technology (xTAG-LCT), as well as ERCC1, TYMS, RRM1, TUBB3, STMN1, TOP2A and VEGFR1-3 mRNA expression detected by branched DNA-liquidchip technology (bDNA-LCT).

Results

Higher rates of low ERCC1 (35.6 vs. 20.3%, P = 0.0105), RRM1 (23.3 vs. 13.0%, P = 0.0437), STMN1 (72.2 vs. 42.8%, P = 0.0000) and high VEGFR2 (34.4 vs. 18.8%, P = 0.0078) mRNA expression were found in EGFR-mutated tumors, suggesting possible benefit from platinum, gemcitabine, taxanes or VEGFR2 inhibitors. Primary lesions showed low ERCC1 (31.6 vs. 18.5%, P = 0.0271), TYMS (17.6 vs. 7.6%, P = 0.0300), TUBB3 (16.9 vs. 7.6%, P = 0.0415), STMN1 (62.1 vs. 42.9%, P = 0.0065) and high TOP2A (48.7 vs. 33.1%, P = 0.0262) mRNA expression and higher KRAS mutations (25.7 vs. 14.1%, P = 0.0350), suggesting platinum, taxanes, pemetrexed, anti-TOP2A agents and resistant to anti-EGFR therapies. Liver metastases showed absence of low TYMS expression, indicating insensitivity to pemetrexed-based regimen. Pleura metastases harbored higher rates of high VEGFR2 expression (50.0 vs. 19.1%, P = 0.0127). Lymph node metastases presented higher rates of high VEGFR2 expression (37.5 vs. 19.1%, P = 0.0253) and EGFR mutations (59.4 vs. 34.4%, P = 0.0011), suggesting use of anti-VEGFR2 and anti-EGFR therapies.

Conclusion

Molecular profiling of 228 lung adenocarcinomas determined a significant difference between biomarkers such as EGFR and KRAS subtypes at primary and metastatic sites. Our results serve as a reference for individual treatment based on different potential targets in metastatic lung adenocarcinoma directed by molecular profiling.

Keywords

Primary tumor Metastatic tumor Lung adenocarcinoma Molecular marker Therapy 

Notes

Acknowledgements

This study was funded by a Research Grant from the Postdoctoral Scientific Research Developmental Fund (Grant No. LBH-Q16143) provided by the administration office of Heilongjiang Postdoctoral Program, China. Our thanks to all participants who consented to take part in this trial.

Funding

This study was funded by a Research Grant from the Postdoctoral Scientific Research Developmental Fund (Grant No. LBH-Q16143) provided by the administration office of Heilongjiang Postdoctoral Program, China.

Compliance with ethical standards

Conflict of interest

The authors declared that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the Ethical Review Committee of Second Affiliated Hospital of Harbin Medical University and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this retrospective study formal consent is not required.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

12094_2018_1906_MOESM1_ESM.docx (17 kb)
Supplementary material 1 (DOCX 17 kb)

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Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2018

Authors and Affiliations

  1. 1.Department of OncologyThe Second Affiliated Hospital of Harbin Medical UniversityHarbinPeople’s Republic of China
  2. 2.Dental HospitalThe First Affiliated Hospital of Harbin Medical UniversityHarbinPeople’s Republic of China
  3. 3.Department of Biopharmaceutical Sciences, College of PharmacyHarbin Medical UniversityHarbinPeople’s Republic of China

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