Abstract
Objectives
Prior researches indicate that peripheral blood CD4 levels have an inverse correlation with distant tumor metastasis in non-small cell lung cancer (NSCLC). However, the linear relationship between CD4 and distant metastasis lacks clarity. Hence, the objective of this study was to ascertain the linear relationship between CD4 and distant metastasis in NSCLC patients.
Methods
This retrospective study analyzed clinical and laboratory data of NSCLC patients between March 2016 and July 2022 at the Cancer Hospital of Anhui University of Technology. The study first applied a generalized summation model and smoothing curve fitting to determine if there was a linear relationship between CD4 and NSCLC metastasis. Secondarily, univariate logistic analysis and multiple linear regression were used to analyze the odds ratio (OR) of CD4 as a continuous variable, dichotomous variable, and trichotomous variable when predicting NSCLC metastasis. In addition, stratified and subgroup analyses were conducted to assess the reliability of CD4 in different NSCLC patient populations.
Results
The study included a total of 213 NSCLC patients, among which 122 had distant metastasis and 91 had no metastasis. The smoothing curve fitting analysis revealed a U-shaped relationship between CD4 and NSCLC metastasis with a threshold effect. The univariate logistic analysis indicated that continuous CD4 expression was not significantly associated with NSCLC metastasis (P = 0.051); however, high levels of CD4 expression (≥ 35.06%) were found to be a protective factor against NSCLC metastasis when CD4+ T was a dichotomous variable (OR = 0.49, P = 0.010). Furthermore, multivariate linear regression models showed that low (< 32%) or high levels (> 44%) of CD4 significantly increased the risk of NSCLC metastasis compared to medium levels (32–44%) when CD4+ T was trichotomized. The significance was maintained in stratified analysis in relation to age, sex, type of pathology, smoke, PS, and T stage. CD4 levels were U-shaped in relation to different sites of distant metastases (bone, brain, liver), but not with lung metastases.
Conclusions
A threshold effect is shown to exist between the peripheral blood CD4 and distant metastasis in NSCLC patients. It was revealed that the risk of distant metastasis is lower when CD4 is maintained between 32 and 44%, whereas low (< 32%) or high (> 44) levels of CD4 are associated with an increased risk of distant metastasis in NSCLC patients.
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Data availability
The data set generated during this systematic review is available from the corresponding author on reasonable request.
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Acknowledgements
We sincerely thank all participants for their help in this study. Thanks to Medical College of Anhui University of Science and Technology and Cancer Hospital of Huainan Oriental Hospital Group.
Funding
This study was supported by the National Natural Science Foundation of China (No. 81971483), the Collaborative Innovation Project of Colleges and Universities of Anhui Province (GXXT-2020-058), and the Graduate Innovation Foundation of AUST (2021CX2124, 2021CX2125, 2021CX2126). Open Research Fund of Anhui Province Engineering Laboratory of Occupational Health and Safety (No. AYZJSGCLK202202001, AYZJSGCLK202201001, AYZJSGCLK202201002). Open Research Fund of Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes (AYZJSGXLK202202002).
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HD and WJ: conception and design, and study supervision. HC, XZ, BY, ZJ, WW, GJ, and SZ: development of methodology, analysis, and interpretation of data, and writing of the manuscript. XY, XJ, and DX: review of the manuscript.
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Ethical approval to report this case series was obtained from Cancer Hospital of Huainan Oriental Hospital Group Medical Research Ethics Committee (No: 2022-KY-FZZX-01).
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Bai, Y., Liu, Y., Wu, J. et al. CD4 levels and NSCLC metastasis: the benefits of maintaining moderate levels. J Cancer Res Clin Oncol 149, 16827–16836 (2023). https://doi.org/10.1007/s00432-023-05418-2
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DOI: https://doi.org/10.1007/s00432-023-05418-2