长链非编码RNA HCP5：一种用于诊断胃癌的潜在生物标志物。

LncRNA HCP5 : A Potential Biomarker for Diagnosing Gastric Cancer.

作者信息

Qin Shiyi, Yang Lei, Kong Shan, Xu Yanhua, Liang Bo, Ju Shaoqing

机构信息

Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China.

Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China.

出版信息

Front Oncol. 2021 Jun 18;11:684531. doi: 10.3389/fonc.2021.684531. eCollection 2021.

DOI:10.3389/fonc.2021.684531

PMID:34222007

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8252797/

Abstract

BACKGROUND

It has been reported that long non-coding RNAs (lncRNAs) can be regarded as a biomarker and had particular clinical significance for early screening and gastric cancer (GC) diagnosis. Therefore, this study aimed to investigate whether serum HCP5 could be a new diagnostic biomarker.

METHODS

Filtered out the HCP5 from the GEO database. The specificity of HCP5 was verified by real-time fluorescence quantitative PCR (qRT-PCR), and then the stability of HCP5 was verified by room temperature storage and repeated freeze-thaw experiments. Meanwhile, the accuracy of HCP5 was verified by agarose gel electrophoresis (AGE) and Sanger sequencing. Simultaneously, the expression level of serum HCP5 was detected by qRT-PCR in 98 patients with primary gastric cancer, 21 gastritis patients, 82 healthy donors, and multiple cancer types. Then, the methodology analysis was carried on. Moreover, receiver operating characteristic (ROC) was used to evaluate its diagnostic efficiency.

RESULTS

qRT-PCR method had good repeatability and stability in detecting HCP5. The expression level of HCP5 in the serum of gastric cancer patients was remarkably higher than that of healthy controls, and it could distinguish gastritis patients from healthy donors. Besides, the expression of HCP5 was increased dramatically in MKN-45 and MGC-803. The FISH assay showed that HCP5 was mainly distributed in the cytoplasm of MKN-45 and BGC-823 cells. When HCP5 was combined with existing tumor markers, the diagnostic efficiency of HCP5 was the best, and the combined diagnosis of carcinoembryonic antigen (CEA), carbohydrate antigen199 (CA199), and HCP5 can significantly improve the diagnostic sensitivity. Besides, compared with the expression levels of thyroid cancer (THCA), colorectal cancer (CRC), and breast cancer (BRCA), serum HCP5 in gastric cancer was the most specific. Moreover, the high expression of serum HCP5 was related to differentiation, lymph node metastasis, and nerve invasion. The term of serum HCP5 after the operation was significantly lower than that of patients with primary gastric cancer.

CONCLUSION

Serum HCP5 can be used as a potential biomarker of non-invasive fluid biopsy, which had a unique value in the early diagnosis, development, and prognosis of gastric cancer.

摘要

背景

据报道，长链非编码RNA（lncRNAs）可作为一种生物标志物，对胃癌（GC）的早期筛查和诊断具有特殊的临床意义。因此，本研究旨在探讨血清HCP5是否可作为一种新的诊断生物标志物。

方法

从GEO数据库中筛选出HCP5。通过实时荧光定量PCR（qRT-PCR）验证HCP5的特异性，然后通过室温保存和反复冻融实验验证HCP5的稳定性。同时，通过琼脂糖凝胶电泳（AGE）和桑格测序验证HCP5的准确性。同时，采用qRT-PCR检测98例原发性胃癌患者、21例胃炎患者、82例健康供体及多种癌症类型患者血清HCP5的表达水平。然后，进行方法学分析。此外，采用受试者工作特征（ROC）曲线评估其诊断效率。

结果

qRT-PCR法检测HCP5具有良好的重复性和稳定性。胃癌患者血清中HCP5的表达水平显著高于健康对照，且能区分胃炎患者和健康供体。此外，MKN-45和MGC-803中HCP5的表达显著增加。荧光原位杂交（FISH）检测显示，HCP5主要分布于MKN-45和BGC-823细胞的细胞质中。当HCP5与现有肿瘤标志物联合使用时，HCP5的诊断效率最佳，癌胚抗原（CEA）、糖类抗原199（CA199）和HCP5联合诊断可显著提高诊断敏感性。此外，与甲状腺癌（THCA）、结直肠癌（CRC）和乳腺癌（BRCA）的表达水平相比，胃癌患者血清HCP5最为特异。此外，血清HCP5高表达与分化、淋巴结转移和神经侵犯有关。术后血清HCP5水平显著低于原发性胃癌患者。