Chung Tony K H, Cheung Tak Hong, Yim So Fan, Yu Mei Yun, Chiu Rossa W K, Lo Keith W K, Lee Ida P C, Wong Raymond R Y, Lau Kitty K M, Wang Vivian W, Worley Michael J, Elias Kevin M, Fiascone Stephen J, Smith David I, Berkowitz Ross S, Wong Yick Fu
Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong.
Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.
Gynecol Oncol. 2017 Aug;146(2):334-339. doi: 10.1016/j.ygyno.2017.05.038. Epub 2017 Jun 3.
Cervical cancer is the fourth most common female cancer worldwide. The prognosis for women with advanced-stage or recurrent cervical cancer remains poor and response to treatment is variable. Standardized management protocols leave little room for individualization. We report on a novel blood-based liquid biopsy for specific PIK3CA mutations as a clinically useful biomarker in patients with invasive cervical cancer.
One hundred seventeen Hong Kong Chinese women with primary invasive cervical cancer and their pre-treatment plasma samples were investigated. Two PIK3CA mutations, p.E542K and p.E545K were measured in cell free DNA (cfDNA) extracted from plasma using droplet digital PCR. This liquid biopsy of PIK3CA in cervical cancer was correlated to clinico-pathological features to verify the potential of PIK3CA as a clinically useful molecular biomarker for predicting disease prognosis and monitoring for progression.
PIK3CA mutations, either p.E542K or p.E545K, were detected in plasma cfDNA from 22.2% of the patients. PIK3CA mutation status was significantly correlated to median tumor size (p<0.01). PIK3CA mutations detected in the plasma were significantly associated with decreased disease-free survival and overall survival (p<0.05).
As a liquid molecular biopsy, analysis of circulating PIK3CA mutations shows promise as a way to refine risk stratification of individual patients with cervical cancer, and provides a platform for further research to offer individualized therapy with the purpose of improving outcomes.
宫颈癌是全球第四大常见女性癌症。晚期或复发性宫颈癌女性的预后仍然很差，对治疗的反应也各不相同。标准化管理方案几乎没有个体化的空间。我们报告了一种针对特定PIK3CA突变的新型血液液体活检，作为浸润性宫颈癌患者临床上有用的生物标志物。
对117名患有原发性浸润性宫颈癌的中国香港女性及其治疗前血浆样本进行了研究。使用液滴数字PCR在从血浆中提取的游离DNA（cfDNA）中检测两种PIK3CA突变，即p.E542K和p.E545K。这种宫颈癌PIK3CA的液体活检与临床病理特征相关，以验证PIK3CA作为预测疾病预后和监测疾病进展的临床有用分子生物标志物的潜力。
22.2%的患者血浆cfDNA中检测到PIK3CA突变，即p.E542K或p.E545K。PIK3CA突变状态与肿瘤中位数大小显著相关（p<0.01）。血浆中检测到的PIK3CA突变与无病生存期和总生存期降低显著相关（p<0.05）。
作为一种液体分子活检，循环PIK3CA突变分析有望作为一种完善宫颈癌个体患者风险分层的方法，并为进一步研究提供一个平台，以提供个体化治疗，目的是改善治疗结果。
