CDKN2A 或 CDKN2B 纯合缺失伴高免疫浸润作为肺腺癌的有利预后因素。,Journal of Clinical Oncology

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CDKN2A 或 CDKN2B 纯合缺失伴高免疫浸润作为肺腺癌的有利预后因素。
Journal of Clinical Oncology ( IF 42.1 ) Pub Date : 2021-05-20 , DOI: 10.1200/jco.2021.39.15_suppl.e20543
Benxu Tan ₁ , Yonghong Chen ₁ , Lei Xia ₁ , Xian Yu ₁ , Yusheng Huang ₁ , Ni Zhang ₁ , Yuan Peng ₁ , Mengmeng Song ₂ , Liyan Ji ₃ , Pansong Li ₂ , Xuefeng Xia ₄ , Zhenzhou Yang ₅

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e20543 背景：CDKN2A 和 CDKN2B 都通过调节细胞周期作为肿瘤抑制基因，在人类中，细胞周期位于第 9 号染色体，p21.3 带。肺腺癌 (LUAD) 中 CDKN2A 和 CDKN2B 中纯合缺失 (HomDel) 的频率分别为 12.5% 和 12.1%。然而，CDKN2A/B HomDel 的 LUAD 患者的基因组、免疫基因组特征及其对预后的影响仍不清楚。方法：本研究的队列来自癌症基因组图谱（TCGA）。LUAD患者共508例，其中CDKN2A/B HomDel（homdel）99例，CDKN2A/B野生（wild）509例。本研究通过分析全外显子组测序 (WES) 和 RNA 测序数据，探讨了 homdel 和野生之间基因组和免疫基因组景观的差异。结果：突变频率最高的基因是 TP53、TTN、MUC16 和 CSMD3。它们在 homdel 和 wild 的频率分别为 46% 和 48%、43% 和 46%、35% 和 41%、33% 和 38%。homdel 和野生之间的肿瘤突变负荷 (TMB) 没有显着差异（中位 TMB，homdel 为 133，野生为 177；Wilcoxon 检验，p = 0.11），临床特征包括年龄、性别、吸烟史和肿瘤分期homdel和wild之间没有显着差异。Homdel 的总生存期 (OS) 比野生型短（对数秩检验，p = 0.04，风险比：0.7，95% CI：0.49-1.02），但无进展生存期 (PFS) 没有显着差异（对数秩检验，p = 0.05，危险比：0.73，95% CI：0.51-1.04）。我们使用单样本基因集富集分析 (ssGSEA) 计算了抗原呈递和 T 细胞介导的免疫等 25 种免疫相关途径的富集评分 (ES)，然后使用共识聚类算法（ConsensusClusterPlus）对homdel和wild分别进行聚类，并分别聚类为低免疫浸润组和高免疫浸润组。对于 homdel 和野生的高免疫浸润和低免疫浸润，高免疫浸润具有更长的 OS（对数秩检验，p = 0.009，危险比：2.19，95% CI：1.22-3.94）和 PFS（对数秩检验）测试，p = 0.044，危险比：1.8，95% CI：1.01-3.2）比 homdel 中的低免疫浸润。然而，在 PFS（对数秩检验，p = 0.28，危险比：1.21，95% CI：0.87-1.68）和 OS（对数秩检验，p = 0.96）方面，高和免疫浸润之间没有显着的异质性, Hazard Ratio: 1.01, 95% CI: 0.71-1.44) 在野生组中，野生组的 OS 比 homdel 组长，免疫浸润低（Log-rank test, p = 0.003, Hazard Ratio: 0.5, 95% CI：0.29-0.88），而与具有高免疫浸润的 homdel 具有相同的 OS，而与免疫浸润无关。PFS 也是如此（对数秩检验，p = 0.005，危险比：0.48，95% CI：0.27-0.82）。结论：CDKN2A/B homdel 是 LUAD 的不利预后因素，但具有高免疫浸润可能会提高患者的生存时间。

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CDKN2A or CDKN2B homozygous deletion with high-immune infiltration as a favorable prognostic factor for lung adenocarcinoma.

e20543 Background: CDKN2A and CDKN2B both acted as tumor suppressor genes by regulating the cell cycle, which in humans were located at chromosome 9, band p21.3. The frequencies of homozygous deletion (HomDel) in CDKN2A and CDKN2B in lung adenocarcinoma (LUAD) were 12.5% and 12.1%, respectively. However, the genomic, immunogenomic features and impact on the prognosis of LUAD patients with CDKN2A/B HomDel were still unclear. Methods: The cohort of this study was from The Cancer Genome Atlas (TCGA). A total of 508 LUAD patients, including 99 CDKN2A/B HomDel (homdel) and 509 CDKN2A/B wild (wild). This study explored the difference of genomic and immunogenomic landscape between homdel and wild by analysis of whole-exome sequencing (WES) and RNA sequencing data. Results: The most frequently mutated genes were TP53, TTN, MUC16, and CSMD3. Their frequencies in homdel and wild are 46% and 48%, 43% and 46%, 35% and 41%, 33% and 38%, respectively. There was no significant difference of tumor mutational burden (TMB) between homdel and wild (median TMB, 133 in homdel vs 177 in wild; Wilcoxon test, p = 0.11), and clinical characteristics including age, gender, smoking history, and tumor stage were not significantly different between homdel and wild. Homdel had a shorter overall survival (OS) than wild (Log-rank test, p = 0.04, Hazard Ratio: 0.7, 95% CI: 0.49-1.02), but there was no significant difference in progression-free survival (PFS) (Log-rank test, p = 0.05, Hazard Ratio: 0.73, 95% CI: 0.51-1.04). We used single sample gene set enrichment analysis (ssGSEA) to calculate the enrichment score (ES) of 25 immune-related pathways such as antigen presentation and T cell-mediated immunity, and then used the consensus clustering algorithm (ConsensusClusterPlus) to cluster homdel and wild respectively, and both clustered into low and high immune infiltration groups. For the high immune infiltration and low immune infiltration in homdel and wild, high immune infiltration had a longer OS (Log-rank test, p = 0.009, Hazard Ratio: 2.19, 95% CI: 1.22-3.94) and PFS (Log-rank test, p = 0.044, Hazard Ratio: 1.8, 95% CI: 1.01-3.2) than low immune infiltration in homdel. However, there was no significant heterogeneity between high and immune infiltration in terms of PFS (Log-rank test, p = 0.28, Hazard Ratio: 1.21, 95% CI: 0.87-1.68) and OS (Log-rank test, p = 0.96, Hazard Ratio: 1.01, 95% CI: 0.71-1.44) in the wild group, the wild group had longer OS than homdel group with low immune infiltration (Log-rank test, p = 0.003, Hazard Ratio: 0.5, 95% CI: 0.29-0.88), while had the same OS with homdel with high immune infiltration, irrespective of immune infiltration. And so was PFS (Log-rank test, p = 0.005, Hazard Ratio: 0.48, 95% CI: 0.27-0.82). Conclusions: CDKN2A/B homdel was an unfavorable prognostic factor for LUAD, but which with high immune infiltration might improve patient survival time.

更新日期：2021-05-20

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