KRAS、NRAS、BRAF和PIK3CA基因突变与结直肠癌患者临床病理特征、预后及无名指蛋白215表达的关系

IF 2.3 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedical reports Pub Date : 2023-10-31 DOI:10.3892/br.2023.1686

Jing-Bo Wu, Xiao-Jing Li, Hui Liu, Yong-Juan Liu, Xiu-Ping Liu

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引用次数: 0

摘要

KRAS、NRAS、BRAF和PIK3CA基因突变与结直肠癌患者临床病理特征及预后的关系尚缺乏研究。此外，无名指蛋白215 (RNF215)在KRAS、NRAS、BRAF和PIK3CA突变的结直肠癌患者中的作用尚不清楚。本研究收集了182例原发性结直肠癌患者的手术切除标本进行回顾性分析。KRAS/NRAS/BRAF/PIK3CA基因突变通过扩增-难解突变系统确认。免疫组化(IHC)检测KRAS、NRAS、BRAF和PIK3CA蛋白表达。RNF215在结直肠癌患者中的表达采用TIMER 2.0数据库和免疫组化检测。KRAS、NRAS、BRAF和PIK3CA的个体突变率分别为40.7%(74/182)、4.4%(8/182)、4.4%(8/182)和3.3%(6/182)。KRAS外显子2突变率最高(61.5%，64/104)，这些突变主要发生在密码子12和13上。KRAS/NRAS/BRAF/PIK3CA野生型CRC患者的总生存期和无病生存期明显长于KRAS/NRAS/BRAF/PIK3CA突变型CRC患者(P<0.05)。总体而言，45.4%(5/11)的PIK3CA突变患者伴有KRAS突变。淋巴结转移患者KRAS/NRAS/BRAF/PIK3CA基因突变率(76.1%，35/46)显著高于无淋巴结转移患者(50.8%，69/136)(P=0.0027)。KRAS、NRAS、BRAF和PIK3CA突变患者与未突变患者的IHC表达差异无统计学意义(P>0.05)。TIMER 2.0分析显示，CRC中突变BRAF组的RNF215表达显著高于野生型BRAF组(P<0.05)。综上所述，KRAS是最常见的突变基因，KRAS突变可能是CRC患者预后不良的因素。KRAS野生型患者耐药可能与PIK3CA基因突变有关，尽管这需要在更大的队列中进一步验证。BRAF突变可能与CRC患者的RNF215表达相关。

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Association of KRAS, NRAS, BRAF and PIK3CA gene mutations with clinicopathological features, prognosis and ring finger protein 215 expression in patients with colorectal cancer

The relationships of KRAS, NRAS, BRAF and PIK3CA gene mutations with the clinicopathological features and prognosis of colorectal cancer (CRC) in patient are lacking. Furthermore, the role of ring finger protein 215 (RNF215) in CRC patients with KRAS, NRAS, BRAF and PIK3CA mutations remains unclear. In the present study, 182 surgical resection specimens from patients with primary CRC for retrospective analysis, were collected. KRAS/NRAS/BRAF/PIK3CA gene mutations were confirmed by an amplification‑refractory mutation system. Immunohistochemistry (IHC) was conducted to confirm KRAS, NRAS, BRAF and PIK3CA protein expression. RNF215 expression in patients with CRC was evaluated using TIMER 2.0 database and IHC. The individual mutation rates of KRAS, NRAS, BRAF and PIK3CA were 40.7% (74/182), 4.4% (8/182), 4.4% (8/182) and 3.3% (6/182), respectively. The KRAS exon 2 mutation rate was the highest (61.5%, 64/104), and these mutations mainly occurred at codons 12 and 13. KRAS/NRAS/BRAF/PIK3CA wild‑type CRC patients had significantly longer overall survival and disease‑free survival than mutated KRAS/NRAS/BRAF/PIK3CA CRC patients (P<0.05). Overall, 45.4% (5/11) of patients with PIK3CA mutations had concomitant KRAS mutations. The KRAS/NRAS/BRAF/PIK3CA gene mutation rate in patients with lymph node metastasis (76.1%, 35/46) was significantly higher than that in patients without lymph node metastasis (50.8%, 69/136) (P=0.0027). There were no significant differences in IHC expression between patients with and without KRAS, NRAS, BRAF and PIK3CA mutations (P>0.05). The TIMER 2.0 analysis showed that RNF215 expression was significantly higher in the mutated BRAF group than in the wild‑type BRAF group in CRC (P<0.05). In conclusion, KRAS is the most commonly mutated gene, and KRAS mutations may be a poor prognostic factor for patients with CRC. KRAS wild‑type patient resistance may be related to PIK3CA gene mutations, although this needs further verification in larger cohorts. BRAF mutations may be associated with RNF215 expression in patients with CRC.

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来源期刊

Biomedical reports MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

4.10

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0.00%

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期刊介绍： Biomedical Reports is a monthly, peer-reviewed journal, dedicated to publishing research across all fields of biology and medicine, including pharmacology, pathology, gene therapy, genetics, microbiology, neurosciences, infectious diseases, molecular cardiology and molecular surgery. The journal provides a home for original research, case reports and review articles.