Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University School of Oncology, Peking University Cancer Hospital & Institute, Beijing, China.
Department of Gastroenterology, Gansu Wuwei Tumor Hospital, Wuwei, China.
Cancer Med. 2023 Jun;12(11):12728-12738. doi: 10.1002/cam4.5905. Epub 2023 Apr 21.
Effective noninvasive biomarkers of gastric cancer (GC) are critical for early detection and improvement of prognosis. We performed genome-wide long non-coding RNA (lncRNA) microarray analysis to identify and validate novel GC biomarkers depending on a high-risk population cohort.
LncRNA profiles were described using the Human LncRNA Microarray between GC and control plasma samples. The differential candidate lncRNAs were validated in two stages by quantitative reverse transcription polymerase chain reaction (qRT-PCR). We further evaluated the joint effect between the GC-associated lncRNA and Helicobacter pylori (H. pylori) infection on the risk of cardia and non-cardia GC, respectively.
Different lncRNA expression profiles were identified between GC and control plasma with a total of 1206 differential lncRNAs including 470 upregulated and 736 downregulated in GC compared with the control group. The eight significantly upregulated lncRNAs (RP11-521D12.1, AC011995.3, RP11-5P4.3, RP11-244 K5.6, RP11-422 J15.1, CTD-2306 M5.1, CTC-428G20.2, and AC009133.20) in GC cases both in the present study and a similar microarray screening study by our collaborative team were selected for a two-stage validation. After the large sample size validation, the subjects with higher expression of RP11-244 K5.6 showed a significantly increased risk of GC with an adjusted odds ratio (OR) as 2.68 and 95% confidence interval (CI) as 1.15-6.24. Joint effects between RP11-244 K5.6 expression and H. pylori infection on the risk of GC were evaluated with no statistical significance.
Our study found different lncRNA expression profiles between GC and control plasma and preliminarily identified RP11-244 K5.6 as a potential noninvasive biomarker for GC screening.
有效的胃癌（GC）非侵入性生物标志物对于早期检测和改善预后至关重要。我们进行了全基因组长非编码 RNA（lncRNA）微阵列分析，以根据高危人群队列鉴定和验证新的 GC 生物标志物。
使用 GC 和对照血浆样本之间的 Human LncRNA Microarray 描述 lncRNA 图谱。通过定量逆转录聚合酶链反应（qRT-PCR）在两个阶段验证差异候选 lncRNA。我们进一步评估了与 GC 相关的 lncRNA 与幽门螺杆菌（H. pylori）感染之间的联合效应对贲门和非贲门 GC 风险的影响。
GC 与对照血浆之间存在不同的 lncRNA 表达谱，与对照组相比，GC 中共有 1206 个差异 lncRNA，包括 470 个上调和 736 个下调。在本研究和我们合作团队的类似微阵列筛选研究中，在 GC 病例中均被选中的 8 个显著上调的 lncRNA（RP11-521D12.1、AC011995.3、RP11-5P4.3、RP11-244 K5.6、RP11-422 J15.1、CTD-2306 M5.1、CTC-428G20.2 和 AC009133.20）用于两阶段验证。在大样本量验证后，RP11-244 K5.6 表达较高的受试者患 GC 的风险显著增加，调整后的优势比（OR）为 2.68，95%置信区间（CI）为 1.15-6.24。未发现 RP11-244 K5.6 表达与 H. pylori 感染对 GC 风险的联合效应有统计学意义。
我们的研究发现 GC 与对照血浆之间存在不同的 lncRNA 表达谱，并初步将 RP11-244 K5.6 鉴定为 GC 筛查的潜在非侵入性生物标志物。
