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Frequently mutated genes in predicting the relapse of stage I lung adenocarcinoma

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Abstract

Purpose

Approximately, 45–65% stage I non-small cell lung cancer (NSCLC) patients with surgical resection relapse within 5 years. Therefore, it is urgent to identify the predictors involved in the relapse of stage I NSCLC.

Methods/patients

Targeted sequencing was used to examine the mutation of tumor tissues and matched adjacent normal tissues from 35 patients with stage I lung adenocarcinoma (LUAD). Then, tissue microarrays containing tumor tissues from 149 stage I LUAD patients were used to assess protein expression of frequently mutated genes by immunohistochemistry. COX regression model was used to evaluate the impacts of frequently mutated genes and their protein expression on relapse-free survival (RFS) in stage I LUAD.

Results and conclusions

Three hundred and twenty-nine non-synonymous somatic variants were identified in 161 genes among these 35 patients. EGFR, TP53, LRP1B, RBM10, KRAS, NTRK3, RB1, ALK, APC, FAT2, KEAP1, MED12 and MLL3 were described as frequently mutated genes with prevalence more than 10%. Patients harboring KRAS mutation had more relapse in 1 year after surgical resection. For the expression of these frequently mutated genes in 149 stage I patients, multivariate Cox regression analyses showed that the expression of RBM10 was positively associated with RFS in all patients (HR 0.40, 95% CI 0.15–1.0, p = 0.052), and the expression of APC was negative associated with RFS in patients with EGFR mutations (HR 3.10, 95% CI 1.54–6.26, p = 0.002). Stage I LUAD patients with KRAS mutation or low RBM10 expression are inclined to receive more positive intervention rather than just disease surveillance.

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Data availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank all the patients for providing clinical samples for this study.

Funding

This study is supported by National Natural Science Foundation of China, No. 8207112270.

Author information

Author notes

  1. Wen Rao and Lujie Yang have contributed equally to this study.

Authors and Affiliations

  1. Cancer Center, Daping Hospital and Army Medical Center of PLA, Army Medical University, No.10 Changjiangzhi Rd, Yuzhong District, Chongqing, People’s Republic of China

    Wen Rao, Lujie Yang, Nan Dai, Liang Zhang, Jie Liu, Bo Yang, Mengxia Li, Jinlu Shan & Dong Wang

  2. The 75th Group Army Hospital, Dali, Yunnan, People’s Republic of China

    Wen Rao

  3. Department of Pathology, Daping Hospital and Army Medical Center of PLA, Army Medical University, Chongqing, People’s Republic of China

    Qiushi Wang

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  1. Wen Rao
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Contributions

DW: conceived and designed the study, WR, ND, LZ, JL and BY: conducted the experiments and data analysis, LY, ML, JS and QW: provided technical support. The first draft of the manuscript was written by WR and LY on previous versions of the manuscript. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Dong Wang.

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Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethical approval

The studies involving human participants were reviewed and approved by Ethics Committee of Daping Hospital (2017 number 30).

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Due to the retrospective nature of the study, informed consent was waived.

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All the patients whose data were retrospectively analyzed were informed of the use of their clinical information under anonymization and received an opportunity to object to use or publication.

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Rao, W., Yang, L., Dai, N. et al. Frequently mutated genes in predicting the relapse of stage I lung adenocarcinoma. Clin Transl Oncol 25, 1767–1778 (2023). https://doi.org/10.1007/s12094-023-03074-z

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