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Background <p>Small cell lung cancer is the most malignant subtype of lung cancer and has a poor prognosis. However, the mechanism is not well understood. The aim of this study was to investigate the characteristics of gene mutation in small cell lung cancer patients and the differences in HLA-I alleles between small cell lung cancer patients and healthy controls, and to explore the effects of gene mutations and specific HLA-I alleles on small-cell lung cancer from the perspective of immune regulation.</p> Methods <p>Differences in HLA-I allele frequencies between the two groups were analyzed in a case-control study. Genetic testing was performed using target gene capture and sequencing method. The association between small cell lung cancer, HLA-I alleles, and gene mutation was analyzed by statistical methods.</p> Results <p>The small cell lung cancer group showed significantly higher HLA-A*11:02 (p &lt; 0.001, OR = 4.693, 95%CI = 1.737–12.677), B*40:01 (p = 0.020, OR = 1.916, 95%CI = 1.101–3.333), and B*55:02 (p = 0.037, OR = 2.565, 95%CI = 1.027–6.408) and significantly lower B*44:03 (p = 0.015, OR = 0.196, 95%CI = 0.046–0.843) and C*06:02 (p = 0.005, OR = 0.369, 95%CI = 0.178–0.765) than the control group. Haplotype analysis results showed that HLA-A*11:01-B*51:01 (p = 0.044, OR = 3.433, 95%CI = 0.959–12.292), A*02:06-C*07:02 (p = 0.005, OR = 11.459, 95%CI = 1.331–98.689), A*11:01-C*07:02 (p = 0.007, OR = 3.040, 95%CI = 1.311–7.047), and B*46:01-C*01:02 (p = 0.048, OR = 2.310, 95%CI = 0.986–5.415) frequencies significantly increased and A*02:01-B*13:02 (p = 0.036, OR &lt; 0.001, 95%CI = 0.000-0.918) and B*13:02-C*06:02 (p = 0.009, OR = 0.108, 95%CI = 0.014–0.810) frequency significantly decreased in small cell lung cancer patients. Three-locus haplotype analysis showed that the differences between small cell lung cancer patients and controls were not statistically significant.</p> Conclusion <p>HLA-A*11:01, B*40:01, and B*55:02 may be the immune modulators associated with susceptibility and HLA-B*44:03 and C*06:02 act as the immune modulators associated with resistance of small cell lung cancer. Haplotypes HLA-A*11:01-B*51:01, A*02:06-C*07:02, A*11:01-C*07:02, and B*46:01-C*01:02 are positively associated with small cell lung cancer. Haplotypes A*02:01-B*13:02 and B*13:02-C*06:02 are negatively associated with small cell lung cancer.</p>

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Small cell lung cancer: relationship with HLA-I alleles and gene mutation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月31日

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  • Xuanpeng Wu,
  • Fei Xue,
  • Tao Jiang,
  • Hao Wang,
  • Ming Ni,
  • Zhikun Jia,
  • Yunfeng Ma,
  • Tianju Wang,
  • Qifei Wu

摘要

Background

Small cell lung cancer is the most malignant subtype of lung cancer and has a poor prognosis. However, the mechanism is not well understood. The aim of this study was to investigate the characteristics of gene mutation in small cell lung cancer patients and the differences in HLA-I alleles between small cell lung cancer patients and healthy controls, and to explore the effects of gene mutations and specific HLA-I alleles on small-cell lung cancer from the perspective of immune regulation.

Methods

Differences in HLA-I allele frequencies between the two groups were analyzed in a case-control study. Genetic testing was performed using target gene capture and sequencing method. The association between small cell lung cancer, HLA-I alleles, and gene mutation was analyzed by statistical methods.

Results

The small cell lung cancer group showed significantly higher HLA-A*11:02 (p < 0.001, OR = 4.693, 95%CI = 1.737–12.677), B*40:01 (p = 0.020, OR = 1.916, 95%CI = 1.101–3.333), and B*55:02 (p = 0.037, OR = 2.565, 95%CI = 1.027–6.408) and significantly lower B*44:03 (p = 0.015, OR = 0.196, 95%CI = 0.046–0.843) and C*06:02 (p = 0.005, OR = 0.369, 95%CI = 0.178–0.765) than the control group. Haplotype analysis results showed that HLA-A*11:01-B*51:01 (p = 0.044, OR = 3.433, 95%CI = 0.959–12.292), A*02:06-C*07:02 (p = 0.005, OR = 11.459, 95%CI = 1.331–98.689), A*11:01-C*07:02 (p = 0.007, OR = 3.040, 95%CI = 1.311–7.047), and B*46:01-C*01:02 (p = 0.048, OR = 2.310, 95%CI = 0.986–5.415) frequencies significantly increased and A*02:01-B*13:02 (p = 0.036, OR < 0.001, 95%CI = 0.000-0.918) and B*13:02-C*06:02 (p = 0.009, OR = 0.108, 95%CI = 0.014–0.810) frequency significantly decreased in small cell lung cancer patients. Three-locus haplotype analysis showed that the differences between small cell lung cancer patients and controls were not statistically significant.

Conclusion

HLA-A*11:01, B*40:01, and B*55:02 may be the immune modulators associated with susceptibility and HLA-B*44:03 and C*06:02 act as the immune modulators associated with resistance of small cell lung cancer. Haplotypes HLA-A*11:01-B*51:01, A*02:06-C*07:02, A*11:01-C*07:02, and B*46:01-C*01:02 are positively associated with small cell lung cancer. Haplotypes A*02:01-B*13:02 and B*13:02-C*06:02 are negatively associated with small cell lung cancer.