Abstract
Background
Lung cancer, with its high morbidity and mortality, presents a major significant public health challenge. CD147, linked to cancer progression and metastasis, is a promising therapeutic target, including for lung cancer. The genetic variation may influence the expression of the gene and consequently the risk of lung cancer. This study aims to investigate single nucleotide polymorphisms (SNPs) in CD147 to understand their association with the risk of develo** lung cancer in the Han Chinese population.
Methods
A hospital-based case–control investigation was conducted, enrolling 700 lung cancer patients and 700 cancer-free controls. TagSNPs were selected using Haploview v4.2, and genotype data from the 1000 Genomes Project database were utilized. The selected SNPs (rs28992491, rs67945626, and rs79361899) within the CD147 gene were evaluated using the improved multiple ligation detection reaction method. Statistical analysis included chi-square tests, logistic regression models, and interaction analyses.
Results
Baseline characteristics of the study population showed no significant differences in gender distribution between cases and controls, but there was a notable difference in smoking rates. No significant associations were found between the three TagSNPs and lung cancer susceptibility in the codominant model. However, stratification analyses revealed interesting findings. Among females, the rs79361899 AA/AG genotype was associated with an increased risk of lung cancer. In individuals aged ≥ 65 years old, the rs28992491 GG and rs79361899 AA genotypes were linked to a higher susceptibility. Furthermore, an interaction analysis demonstrated significant genotype × gender interactions in the rs79361899 recessive model, indicating an increased lung cancer risk in female carriers of the heterozygous or homozygous polymorphic genotype.
Conclusions
CD147 polymorphisms play an important role in lung cancer development, particularly in specific subgroup of age and gender. These findings highlight the significance of incorporating genetic variations and their interactions with demographic factors in comprehending the intricate etiology of lung cancer.
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1 Introduction
Complex diseases, such as cancer, arise from the intricate interplay of numerous genetic and environmental factors, most of which exert a relatively modest impact. Genetic variations, specifically Single Nucleotide Polymorphisms (SNPs), are expected to play a significant role in determining susceptibility to complex diseases like cancer. Lung cancer is one of the most prevalent and deadly malignancies worldwide [1]. Understanding the genetic factors associated with lung cancer susceptibility can provide valuable insights into its pathogenesis and potentially lead to improved prevention and treatment strategies.
CD147, also known as basigin or extracellular matrix metalloproteinase inducer (EMMPRIN/Basigin), a type I transmembrane glycoprotein, is a glycoprotein initially known as a regulator of matrix metalloproteinase (MMPs), and inhibition of CD147 may represent a promising therapeutic strategy [2]. Previous studies have shown that CD147 interacts with caveolin-1 [3], MCT1, MCT4 [4], and beta1-integrins [5]. CD147, a multifunctional molecule implicated in the progression and metastasis of cancer, has significant therapeutic potential in diverse diseases, encompassing lung cancer, inflammation, and even COVID-19 [6]. The inhibition of CD147 via Thai traditional medicines [7] and targeted agents such as Formosanin C has demonstrated promising outcomes in reducing CD147 expression levels and impeding the advancement of non-small-cell lung cancer by disrupting MCT4/CD147-mediated lactate export [8]. CD147 is significantly upregulated in multiple cancers and some studies showed that CD147 expression was associated with the worse overall survival (OS) [36].
One of the significant strengths of our study is the similarity in allele frequency differences between our study and all population (African, American, East Asian, European and South Asian) (Ensembl database, release 111). This similarity potentially enables the generalization of our results to a wider range of populations.
We must acknowledge several limitations in our study. Firstly, the relatively modest sample size might have constrained the statistical power to identify small effect size. Secondly, despite adjusting for known confounding factors like age and smoking status, there may still be residual confounding or unmeasured variables. Nonetheless, further comprehensive research is planned to be conducted in the future, including replication studies involving diverse ethnic groups and meta-analyses. These endeavors will facilitate the assessment of the consistency of our findings across diverse populations.
The study findings offer valuable insights for improving lung cancer risk assessment, particularly in Chinese population. Although no significant associations were found between these three TagSNPs of CD147 and lung cancer susceptibility in the general population, stratification analyses revealed important subgroup-specific risks. For females, the rs79361899 AA and AG genotype are associated with the increased lung cancer risk and an interaction analysis demonstrate significant gene × gender interactions in the rs79361899 recessive model, which suggesting the need for gender-specific genetic screening. Similarly, the rs28992491 GG and rs79361899 AA genotype are linked to higher lung cancer susceptibility in individuals aged 65 and older, indicating that the important for considering age-specific genetic factors in lung cancer risk assessment.
Future studies should involve diverse ethnic groups to determine the wider applicability of our findings across different populations. Additionally, exploring the biological mechanisms by which CD147 polymorphisms influence lung cancer susceptibility will provide deeper insights into the role of CD147 in cancer progression.
In conclusion, our study investigated the association between CD147 gene polymorphisms and the risk of lung cancer in a Han Chinese population and uncovered potential gender and age-specific effects of specific genotypes on lung cancer susceptibility. These findings highlight the significance of incorporating genetic variations and their interactions with demographic factors in comprehending the intricate etiology of lung cancer.
Data availability
The raw data supporting the conclusion of this article will be provided upon request by the authors (Yuning **e, xyn0634@gmail.com).
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Funding
This work was supported by Key Project of Natural Science Foundation of Hebei province of China (No. H2017209233) and Leader talent cultivation plan of innovation team in Hebei province (No. LJRC001).
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**e YN and Zhang XM authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Zhou XL, Wu HJ and Li A. The first draft of the manuscript was written by **e YN and Huang C, all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the institutional review board of the Human Ethics Review Committee of North China University of Science and Technology (Ethics approval number: 12–002). Informed consent was obtained from all individual participants included in the study.
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**e, Y., Huang, C., Zhou, X. et al. CD147 TagSNP is associated with the vulnerability to lung cancer in the Chinese population: a case–control study. Discov Onc 15, 281 (2024). https://doi.org/10.1007/s12672-024-01155-1
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DOI: https://doi.org/10.1007/s12672-024-01155-1