CDKN2A somatic copy number amplification in normal tissues surrounding gastric carcinoma reduces cancer metastasis risk in droplet digital PCR analysis.

IF 6 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gastric Cancer Pub Date : 2024-09-01 Epub Date: 2024-06-01 DOI:10.1007/s10120-024-01515-4

Lewen Deng, Jing Zhou, Yu Sun, Ying Hu, Juanli Qiao, Zhaojun Liu, Liankun Gu, Dongmei Lin, Lianhai Zhang, Dajun Deng

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引用次数: 0

Abstract

Background: The CDKN2A gene is frequently affected by somatic copy number variations (SCNVs, including deletions and amplifications [SCNdel and SCNamp]) in the cancer genome. Using surgical gastric margin tissue samples (SMs) as the diploid reference in SCNV analysis via CDKN2A/P16-specific real-time PCR (P16-Light), we previously reported that the CDKN2A SCNdel was associated with a high risk of metastasis of gastric carcinoma (GC). However, the status of CDKN2A SCNVs in SMs and their clinical significance have not been reported.

Methods: Peripheral white blood cell (WBC) and frozen GC and SM tissue samples were collected from patients (n = 80). Droplet digital PCR (ddPCR) was used to determine the copy number (CN) of the CDKN2A gene in tissue samples using paired WBCs as the diploid reference.

Results: A novel P16-ddPCR system was initially established with a minimal proportion (or limit, 10%) of the detection of CDKN2A CN alterations. While CDKN2A SCNamp events were detected in both SMs and GCs, fewer CDKN2A SCNdel events were detected in SMs than in GCs (15.0% vs. 41.3%, P = 4.77E-04). Notably, significantly more SCNamp and fewer SCNdel of the CDKN2A gene were detected in SMs from GC patients without metastasis than in those from patients with lymph node metastasis by P16-ddPCR (P = 0.023). The status of CDKN2A SCNVs in SM samples was significantly associated with overall survival (P = 0.032). No cancer deaths were observed among the 11 patients with CDKN2A SCNamp.

Conclusion: CDKN2A SCNVs in SMs identified by P16-ddPCR are prevalent and significantly associated with GC metastasis and overall survival.

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在液滴数字 PCR 分析中，胃癌周围正常组织中 CDKN2A 体细胞拷贝数扩增可降低癌症转移风险。

背景：在癌症基因组中，CDKN2A基因经常受到体细胞拷贝数变异（SCNVs，包括缺失和扩增[SCNdel和SCNamp]）的影响。在通过 CDKN2A/P16 特异性实时 PCR（P16-Light）进行 SCNV 分析时，我们使用手术胃缘组织样本（SMs）作为二倍体参考，之前曾报道 CDKN2A SCNdel 与胃癌（GC）的高转移风险有关。然而，CDKN2A SCNVs在SMs中的状态及其临床意义尚未见报道：方法：收集患者（80 人）的外周白细胞（WBC）和冷冻 GC 和 SM 组织样本。采用液滴数字 PCR（ddPCR）测定组织样本中 CDKN2A 基因的拷贝数（CN），以配对白细胞作为二倍体参考：结果：最初建立的新型 P16-ddPCR 系统检测到 CDKN2A 基因 CN 改变的比例（或极限，10%）极小。虽然在 SMs 和 GCs 中都检测到了 CDKN2A SCNamp 事件，但在 SMs 中检测到的 CDKN2A SCNdel 事件少于在 GCs 中检测到的 CDKN2A SCNdel 事件（15.0% vs. 41.3%，P = 4.77E-04）。值得注意的是，通过P16-ddPCR，在未转移的GC患者的SMs中检测到的CDKN2A基因SCNamp明显多于淋巴结转移患者的SMs（P = 0.023），而SCNdel则明显少于淋巴结转移患者的SMs（P = 0.023）。SM 样本中 CDKN2A SCNVs 的状态与总生存期显著相关（P = 0.032）。在11例CDKN2A SCNamp患者中，未发现癌症死亡病例：结论：通过 P16-ddPCR 鉴定出的 SM 中的 CDKN2A SCNVs 普遍存在，且与 GC 转移和总生存期显著相关。

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来源期刊

Gastric Cancer 医学-胃肠肝病学

CiteScore

14.70

自引率

2.70%

发文量

审稿时长

6-12 weeks

期刊介绍： Gastric Cancer is an esteemed global forum that focuses on various aspects of gastric cancer research, treatment, and biology worldwide. The journal promotes a diverse range of content, including original articles, case reports, short communications, and technical notes. It also welcomes Letters to the Editor discussing published articles or sharing viewpoints on gastric cancer topics. Review articles are predominantly sought after by the Editor, ensuring comprehensive coverage of the field. With a dedicated and knowledgeable editorial team, the journal is committed to providing exceptional support and ensuring high levels of author satisfaction. In fact, over 90% of published authors have expressed their intent to publish again in our esteemed journal.