Abstract
Purpose
To explore the relationship between Mycoplasma hyorhinis infection and tyrosine kinase inhibitor (TKI) resistance in lung adenocarcinoma patients.
Methods
Mycoplasma hyorhinis infection can be verified with the monoclonal antibody PD4, which specifically recognizes a distinct protein of M. hyorhinis. Immunohistochemistry (IHC), using PD4 to detect M. hyorhinis, was performed on paraffin-embedded lung adenocarcinoma tissues of patients who had epidermal growth factor (EGFR) mutations and had received oral TKI. The number of patients enrolled in our study was 101. Assessments following TKI treatment were performed until objective disease progression or stable disease at the cutoff date was reached. In all of the patients, the primary endpoint was investigator-assessed progression-free survival (PFS).
Results
Immunohistochemistry revealed that 61 of 101 cases (60.4%) of lung adenocarcinoma were positive for M. hyorhinis, which comprised of 31 low-positive cases and 30 high-positive cases; the remaining 40 cases (39.6%) were negative. The median PFS was significantly longer in the negative group [18 months (95% CI 14.15–21.85)] than in the low-positive group [10 months (95% CI 7.70–12.30); hazard ratio (HR) 4.095, 95% CI 2.254–7.438; p < 0.001] and in the high-positive group [4 months (95% CI 2.85–5.15); HR 31.703, 95% CI 14.425–69.678; p < 0.001]. The results of the subgroup analysis were satisfactory. The PFS benefit with negative M. hyorhinis infection was consistent across subgroups.
Conclusions
In this retrospective, exploratory analysis, M. hyorhinis infection significantly reduced PFS. With increased levels of M. hyorhinis infection, the progression of the disease was more advanced, likely due to the hydrolysis of TKI by M. hyorhinis. A strong correlation was found between M. hyorhinis infection and TKI resistance in lung adenocarcinoma. This study provides potent evidence that M. hyorhinis hydrolyses TKI and will assist in the research of related mechanisms in the future.
Implications for cancer survivors
It provides an option to improve the efficacy of TKI, including strategies to decrease M. hyorhinis infection, thereby reducing long-term distress in TKI resistance patients with EGFR mutations.
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Acknowledgments
We are grateful to all participants for taking part in this study. At the same time, we also thank Dr. Chengchao Shou for providing the Sheep Serum named PD4.
Funding
This study was supported by the Chinese Society of Clinical Oncology. Project (Y-HR2018-086).
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Contributions
WH and QS: study design. YD and FZ: literature search, data collection, data analysis, and manuscript drafting. WH and QS contributed equally to this work, as two co-corresponding authors.
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The authors declare that they have no conflict of interest.
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The study design was approved by the Medical Ethics Committee of Renmin Hospital of Wuhan University.
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Informed consent was obtained from all patients and all clinical investigations were conducted according to the ethical and legal standards.
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Dai, Y., Zhong, F., Liu, W. et al. Mycoplasma hyorhinis infection promotes tyrosine kinase inhibitor (TKI) resistance in lung adenocarcinoma patients. J Cancer Res Clin Oncol 147, 1379–1388 (2021). https://doi.org/10.1007/s00432-021-03547-0
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DOI: https://doi.org/10.1007/s00432-021-03547-0