| 摘要: |
| 目的 分析神经母细胞瘤大鼠肉瘤病毒癌基因同源物（NRAS）基因突变结直肠癌（CRC）患者的临床病理特征与其肿瘤组织中Kirsten大鼠肉瘤病毒癌基因同源物（KRAS）、磷脂酰肌醇4,5-二磷酸3-激酶催化亚基α（PIK3CA）、v-raf鼠科肉瘤病毒癌基因同源物B1（BRAF）基因突变状态及错配修复（MMR）蛋白、人表皮生长因子受体2（HER-2）蛋白表达的关系。方法 回顾性分析546例NRAS基因突变CRC患者的临床病理资料。采用基因突变联合检测试剂盒（荧光PCR法）检测NRAS、KRAS、PIK3CA、BRAF基因的突变状态，采用免疫组织化学染色EnVision法检测MMR、HER-2蛋白的表达情况，并分析它们与患者临床病理特征的关系。结果 NRAS基因突变CRC患者中，NRAS基因单一位点突变者占98.35%（537/546），NRAS基因双位点突变者占1.65%（9/546），NRAS和KRAS基因同时突变者占1.47%（8/546），未检出PIK3CA、BRAF基因突变的患者。NRAS基因突变类型包括Q61R（或Q61K、Q61L、Q61H）突变（266/546，48.72%）、G12D（或G12S）突变（154/546，28.21%）、G13R（或G12C、G12V、G12A、G13V）突变（134/546，24.54%）和A146T突变（1/546，0.18%）。其中，G13R（或G12C、G12V、G12A、G13V）突变更容易发生在原发于直肠的CRC患者（P＝0.035）；与该位点未突变患者相比，突变患者虽然肿瘤最大径更大（P＝0.029），但患者术后无进展生存期更长（P＝0.028）。在NRAS基因突变的患者中，HER-2阳性与神经周围浸润相关（P＝0.003），MMR蛋白表达缺陷的患者平均年龄更小（P＝0.041）且与NRAS双位点突变相关（P＝0.018）。结论 NRAS基因突变CRC可能具有独特的临床病理表现与分子表型，为后续CRC的个体化治疗和预后评估提供了潜在依据。 |
| 关键词: 结直肠肿瘤 NRAS基因突变 临床病理特征 错配修复蛋白 人表皮生长因子受体2 |
| DOI：10.16781/j.CN31-2187/R.20240838 |
| 投稿时间：2024-12-09修订日期：2025-02-18 |
| 基金项目:上海市科学技术委员会科技创新行动计划医学创新研究专项（21Y11912900）. |
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| Clinicopathological and molecular genetic characteristics of colorectal cancer with NRAS mutations |
| JIANG Yingjie1,LIU Yan2,SUN Bo2,HE Zongjie1,DING Dan1,BAI Chenguang1* |
(1. Department of Pathology, The First Affiliated Hospital of Naval Medical University (Second Military Medical University), Shanghai 200433, China;
2. College of Basic Medical Sciences, Naval Medical University (Second Military Medical University), Shanghai 200433, China
*Corresponding author) |
| Abstract: |
| Objective To analyze the mutation status of Kirsten rat sarcoma viral oncogene homolog (KRAS), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), v-raf murine sarcoma viral oncogene homolog B1 (BRAF) genes, and the expression of mismatch repair (MMR) and human epidermal growth factor receptor 2 (HER-2) proteins in tumor tissues of patients with colorectal cancer (CRC) harboring neuroblastoma rat sarcoma viral oncogene homolog (NRAS) gene mutations, and explore their relationships with the clinicopathological characteristics of CRC patients. Methods The clinicopathological data of 546 patients with NRAS mutation CRC were retrospectively analyzed. The mutation status of NRAS, KRAS, PIK3CA, and BRAF genes was detected by AmoyDx amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR) kit (fluorescent PCR method), the expression levels of MMR and HER-2 proteins were detected by immunohistochemical staining EnVision method, and the relationship between them and the clinicopathological characteristics of patients were analyzed. Results The mutation rate of single-point mutations in the NRAS gene was 98.35% (537/546), double-point mutations in the NRAS gene were 1.65% (9/546), and double mutations in the NRAS and KRAS genes were 1.47% (8/546). No patients were found to harbor mutations in the PIK3CA or BRAF genes. The types of NRAS mutations included Q61R (or Q61K, Q61L, Q61H) mutations (266/546, 48.72%), G12D (or G12S) mutations (154/546, 28.21%), G13R (or G12C, G12V, G12A, G13V) mutations (134/546, 24.54%), and A146T mutation (1/546, 0.18%). G13R (or G12C, G12V, G12A, G13V) mutations in the NRAS gene were more likely to occur in the rectum cancer patients (P＝0.035); although the tumors had a larger diameter (P＝0.029), the patients had a longer progression-free survival after surgery (P＝0.028). Among patients with NRAS gene mutations, HER-2 positive expression was associated with perineural invasion (P＝0.003), and the patients with deficient MMR were younger on average (P＝0.041) and were associated with double-point mutations in the NRAS gene (P＝0.018). Conclusion CRC harboring NRAS mutations may have unique clinicopathological characteristics and molecular phenotypes, providing possibilities for individualized treatment and prognosis evaluation of CRC. |
| Key words: colorectal neoplasms NRAS mutations clinicopathological characteristics mismatch repair protein human epidermal growth factor receptor 2 |
