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A tumor microenvironment-related mRNA–ncRNA signature for prediction early relapse and chemotherapeutic sensitivity in early-stage lung adenocarcinoma

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Objectives

Postoperative early relapse of early-stage lung adenocarcinoma is implicated in poor prognosis. The purpose of our study was to develop an integrated mRNA and non-coding RNA (ncRNA) signature to identify patients at high risk of early relapse in stage I–II lung adenocarcinoma who underwent complete resection.

Methods

Early-stage lung adenocarcinoma data from Gene Expression Omnibus database were divided into training set and testing set. Propensity score matching analysis was performed between patients in early relapse group and long-term nonrelapse group from training set. Transcriptome analysis, random survival forest and LASSO Cox regression model were used to build an early relapse-related multigene signature. The robustness of the signature was evaluated in testing set and RNA-Seq dataset from The Cancer Genome Atlas (TCGA). The chemotherapy sensitivity, tumor microenvironment and mutation landscape related to the signature were explored using bioinformatics analysis.

Results

Twelve mRNAs and one ncRNA were selected. The multigene signature achieved a strong power for early relapse prediction in training set (HR 3.19, 95% CI 2.16–4.72, P < 0.001) and testing set (HR 2.91, 95% CI 1.63–5.20, P = 0.002). Decision curve analyses revealed that the signature had a good clinical usefulness. Groups divided by the signature exhibited different chemotherapy sensitivity, tumor microenvironment characteristics and mutation landscapes.

Conclusions

Our results indicated that the integrated mRNA–ncRNA signature may be an innovative biomarker to predict early relapse of early-stage lung adenocarcinoma, and may provide more effective treatment strategies.

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Data availability

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Funding

This work was supported by the National Natural Science Foundation of China (81930073), Shanghai Municipal Science and Technology Major Project (Grant No. 2017SHZDZX01, VBH1323001/026), Shanghai Municipal Key Clinical Specialty Project (SHSLCZDZK02104), and Pilot Project of Fudan University (IDF159034), Shanghai Sailing Program 19YF1408800.

Author information

Author notes

  1. Zhendong Gao, Han Han, Yue Zhao, and Hui Yuan have contributed equally to this work.

Authors and Affiliations

  1. Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudand University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China

    Zhendong Gao, Han Han, Yue Zhao, Hui Yuan, Shanbo Zheng, Yang Zhang & Haiquan Chen

  2. Institute of Thoracic Oncology, Fudan University, Shanghai, 200032, China

    Zhendong Gao, Han Han, Yue Zhao, Hui Yuan, Shanbo Zheng, Yang Zhang & Haiquan Chen

  3. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    Zhendong Gao, Han Han, Yue Zhao, Hui Yuan, Shanbo Zheng, Yang Zhang & Haiquan Chen

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  1. Zhendong Gao
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  2. Han Han
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  3. Yue Zhao
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Corresponding author

Correspondence to Haiquan Chen.

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Conflict of interest

Zhendong Gao declares that he has no conflict of interest. Han Han declares that he has no conflict of interest. Yue Zhao declares that he has no conflict of interest. Hui Yuan declares that he has no conflict of interest. Shanbo Zheng declares that he has no conflict of interest. Zhang Yang declares that he has no conflict of interest. Haiquan Chen declares that he has no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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432_2021_3718_MOESM2_ESM.tiff

Supplementary file2 (TIFF 1390 KB) Principal components plot of the first two principal components. (a) Before batch removing. (b) After batch removing.

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Gao, Z., Han, H., Zhao, Y. et al. A tumor microenvironment-related mRNA–ncRNA signature for prediction early relapse and chemotherapeutic sensitivity in early-stage lung adenocarcinoma. J Cancer Res Clin Oncol 147, 3195–3209 (2021). https://doi.org/10.1007/s00432-021-03718-z

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  • DOI: https://doi.org/10.1007/s00432-021-03718-z

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