Ranjbar Reza, Mohammadpour Somayeh, Torshizi Esfahani Amir, Namazian Sina, Yaghob-Taleghani Mohammad, Baghaei Kaveh, Mortazavi Tabatabaei Seyed Abdolreza, Pasharavesh Leila, Nazemalhosseini-Mojarad Ehsan
Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Gastroenterol Hepatol Bed Bench. 2019;12(Suppl1):S22-S29.
This study aimed to evaluate the distribution of PIK3CA E545K mutation in Iranian CRC patients and explored its roles in disease prognosis.
Deregulation of the phosphoinositide 3-kinase (PI3K) pathway contributes to the progression of tumors. The p110a (PIK3CA), a catalytic subunit of PIK3, is mutated in many types of cancers. Exon 9 (E545K) is the most frequently mutated hotspot in PIK3CA in colorectal cancer (CRC). However, the prognostic role of PIK3CA E545K mutation needs to be elucidated.
Tumors from 187 CRC patients were retrospectively collected from the Taleghani and Shohada Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran, between 2010 and 2017. PIK3CA E545K status was detected in Formalin-fixed paraffin-embedded (FFPE) tissues using PCR-RFLP methods, and validated by pyrosequencing. Correlations between PIK3CA E545K mutation clinicopathological features were analyzed.
The frequency of PIK3CA E545K gene mutations in CRC patients was 10.7%. Significant correlations were observed in PIK3CA E545K mutation with tumor differentiation and TNM stage (p < 0.042 and p = 0.033, respectively). Kaplan-Meier analysis showed a worse prognosis in overall survival (OS) in patients with PIK3CA E545K mutation (p < 0.001). Multivariate analysis indicated that PIK3CA E545K mutation was a detrimental factor for OS (HR = 6.497, 95% CI: 2.859-14.768, p < 0.021).
A high frequency of PIK3CA E545K mutation was detected in Iranian CRC patients. The results of the present study suggested that PIK3CA E545K mutation may be associated with poor prognosis. These findings require further confirmation via prospective studies with larger samples.
本研究旨在评估伊朗结直肠癌（CRC）患者中PIK3CA E545K突变的分布情况，并探讨其在疾病预后中的作用。
磷酸肌醇3-激酶（PI3K）信号通路失调促进肿瘤进展。PI3K的催化亚基p110α（PIK3CA）在多种癌症中发生突变。外显子9（E545K）是结直肠癌（CRC）中PIK3CA最常见的突变热点。然而，PIK3CA E545K突变的预后作用尚待阐明。
回顾性收集2010年至2017年间来自伊朗德黑兰沙希德·贝赫什提医科大学塔莱加尼医院和烈士医院的187例CRC患者的肿瘤组织。采用PCR-RFLP方法检测福尔马林固定石蜡包埋（FFPE）组织中的PIK3CA E545K状态，并通过焦磷酸测序进行验证。分析PIK3CA E545K突变与临床病理特征之间的相关性。
CRC患者中PIK3CA E545K基因突变频率为10.7%。PIK3CA E545K突变与肿瘤分化和TNM分期显著相关（分别为p < 0.042和p = 0.033）。Kaplan-Meier分析显示，PIK3CA E545K突变患者的总生存期（OS）预后较差（p < 0.001）。多因素分析表明，PIK3CA E545K突变是OS的不利因素（HR = 6.497，95%CI：2.859 - 14.768，p < 0.021）。
在伊朗CRC患者中检测到较高频率的PIK3CA E545K突变。本研究结果提示PIK3CA E545K突变可能与预后不良有关。这些发现需要通过更大样本的前瞻性研究进一步证实。
