Guo Xin, Peng Yunhua, Song Qiying, Wei Jiangpeng, Wang Xinxin, Ru Yi, Xu Shenhui, Cheng Xin, Li Xiaohua, Wu Di, Chen Lubin, Wei Bo, Lv Xiaohui, Ji Gang
Department of Digestive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China; Department of Endoscopic Surgery, Air Force 986(th) Hospital, Fourth Military Medical University, Xi'an, China; Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China.
Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Gastroenterology. 2023 Aug;165(2):402-413.e13. doi: 10.1053/j.gastro.2023.02.044. Epub 2023 Mar 7.
BACKGROUND & AIMS: Diagnosing gastric cancer (GC) while the disease remains eligible for surgical resection is challenging. In view of this clinical challenge, novel and robust biomarkers for early detection thus improving prognosis of GC are necessary. The present study is to develop a blood-based long noncoding RNA (LR) signature for the early-detection of GC.
The present 3-step study incorporated data from 2141 patients, including 888 with GC, 158 with chronic atrophic gastritis, 193 with intestinal metaplasia, 501 healthy donors, and 401 with other gastrointestinal cancers. The LR profile of stage I GC tissue samples were analyzed using transcriptomic profiling in discovery phase. The extracellular vesicle (EV)-derived LR signature was identified with a training cohort (n = 554) and validated with 2 external cohorts (n = 429 and n = 504) and a supplemental cohort (n = 69).
In discovery phase, one LR (GClnc1) was found to be up-regulated in both tissue and circulating EV samples with an area under the curve (AUC) of 0.9369 (95% confidence interval [CI], 0.9073-0.9664) for early-stage GC (stage I/II). The diagnostic performance of this biomarker was further confirmed in 2 external validation cohorts (Xi'an cohort, AUC: 0.8839; 95% CI: 0.8336-0.9342; Beijing cohort, AUC: 0.9018; 95% CI: 0.8597-0.9439). Moreover, EV-derived GClnc1 robustly distinguished early-stage GC from precancerous lesions (chronic atrophic gastritis and intestinal metaplasia) and GC with negative traditional gastrointestinal biomarkers (CEA, CA72-4, and CA19-9). The low levels of this biomarker in postsurgery and other gastrointestinal tumor plasma samples indicated its GC specificity.
EV-derived GClnc1 serves as a circulating biomarker for the early detection of GC, thus providing opportunities for curative surgery and improved survival outcomes.
在胃癌（GC）仍适合手术切除时进行诊断具有挑战性。鉴于这一临床挑战，需要新的、可靠的生物标志物用于早期检测，从而改善GC的预后。本研究旨在开发一种基于血液的长链非编码RNA（LR）标志物用于GC的早期检测。
本三步研究纳入了2141例患者的数据，包括888例GC患者、158例慢性萎缩性胃炎患者、193例肠化生患者、501例健康供体以及401例其他胃肠道癌症患者。在发现阶段，使用转录组分析对I期GC组织样本的LR谱进行分析。通过一个训练队列（n = 554）鉴定细胞外囊泡（EV）衍生的LR标志物，并在2个外部队列（n = 429和n = 504）以及一个补充队列（n = 69）中进行验证。
在发现阶段，发现一种LR（GClnc1）在组织和循环EV样本中均上调，对于早期GC（I/II期），其曲线下面积（AUC）为0.9369（95%置信区间[CI]，0.9073 - 0.9664）。该生物标志物的诊断性能在2个外部验证队列中得到进一步证实（西安队列，AUC：0.8839；95% CI：0.8336 - 0.9342；北京队列，AUC：0.9018；95% CI：0.8597 - 0.9439）。此外，EV衍生的GClnc1能够可靠地区分早期GC与癌前病变（慢性萎缩性胃炎和肠化生）以及传统胃肠道生物标志物（CEA、CA72 - 4和CA19 - 9）为阴性的GC。该生物标志物在术后和其他胃肠道肿瘤血浆样本中的低水平表明了其对GC的特异性。
EV衍生的GClnc1可作为GC早期检测的循环生物标志物，从而为根治性手术和改善生存结果提供机会。
