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循环lncRNA EGFR-AS1作为结直肠癌的诊断生物标志物和肿瘤负荷指标。

Circulating lncRNA EGFR-AS1 as a diagnostic biomarker of colorectal cancer and an indicator of tumor burden.

作者信息

Dai Weiping, Wang Zhan, Liang Xiaoben, Wang Miaomiao, Ni Wanliu, Yang Ye, Zang Yuan-Sheng

机构信息

Department of Oncology, Second Affiliated Hospital of Navy Medical University, Shanghai, China.

E.N.T. Department, Children's Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai, China.

出版信息

J Gastrointest Oncol. 2022 Oct;13(5):2439-2446. doi: 10.21037/jgo-22-968.

Abstract

BACKGROUND

Colorectal cancer (CRC) is one of the most common malignancies. Although CRC treatment has been significantly improved, patient survival remains low because most patients already have advanced disease at diagnosis. Early screening and diagnosis of tumors is critical; however, the current tissue biopsy and radiological evaluation methods have very limited effectiveness. Therefore, establishing new convenient and non-invasive biomarkers is urgently needed for timely detection, therapeutic assessment, and prognostic prediction. At present, non-coding RNAs (ncRNAs) have attracted research attention owing to their potential oncological applications.

METHODS

The long ncRNA epidermal growth factor receptor antisense RNA 1 (EGFR-AS1) is overexpressed in multiple malignancies including CRC. The present study examined the circulating EGFR-AS1 level in CRC, and the results showed that EGFR-AS1 could be considered an indicator of tumor burden.

RESULTS

Elevated circulating EGFR-AS1 levels were detected in CRC cases (n=128) compared with control cases comprising endoscopy confirmed CRC-free individuals [n=64, median expression normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 1.578 0.780, P<0.001]. Individuals with larger tumors (≥5 cm) had elevated circulating EGFR-AS1 levels compared to those with smaller tumors (<5 cm, 1.739 1.290, P<0.001). The expression of serum EGFR-AS1 in stage III/IV CRC was higher than that in stage I/II CRC (1.691 1.412, P<0.05). Plasma EGFR-AS1 levels were markedly reduced following surgical resection of colorectal lesions in a subset of patients [n=32, 1.192 (pre-surgery) 0.692, P<0.001]. Furthermore, the expression of EGFR-AS1 in resected CRC tissues was significantly higher than that in paracancerous tissues (n=32, 1.336 0.487, P<0.001).

CONCLUSIONS

These results highlight the potential of EGFR-AS1 as a diagnostic biomarker in CRC.

摘要

背景

结直肠癌(CRC)是最常见的恶性肿瘤之一。尽管CRC的治疗已有显著改善,但患者生存率仍然较低,因为大多数患者在诊断时已处于晚期疾病阶段。肿瘤的早期筛查和诊断至关重要;然而,目前的组织活检和影像学评估方法效果非常有限。因此,迫切需要建立新的便捷、非侵入性生物标志物用于及时检测、治疗评估和预后预测。目前,非编码RNA(ncRNAs)因其潜在的肿瘤学应用而受到研究关注。

方法

长链非编码RNA表皮生长因子受体反义RNA 1(EGFR-AS1)在包括CRC在内的多种恶性肿瘤中过表达。本研究检测了CRC患者循环中EGFR-AS1水平,结果表明EGFR-AS1可被视为肿瘤负荷的指标。

结果

与由内镜检查确认无CRC的个体组成的对照病例(n = 64,以甘油醛-3-磷酸脱氢酶(GAPDH)标准化后的中位表达,1.578 ± 0.780,P < 0.001)相比,CRC病例(n = 128)中检测到循环EGFR-AS1水平升高。与肿瘤较小(<5 cm)的个体相比,肿瘤较大(≥5 cm)的个体循环EGFR-AS1水平升高(1.739 ± 1.290,P < 0.001)。III/IV期CRC患者血清EGFR-AS1的表达高于I/II期CRC患者(1.691 ± 1.412,P < 0.05)。在一部分患者(n = 32)中,结直肠病变手术切除后血浆EGFR-AS1水平显著降低[术前1.192 ± 0.692,P < 0.001]。此外,切除的CRC组织中EGFR-AS1的表达显著高于癌旁组织(n = 32,1.336 ± 0.487,P < 0.001)。

结论

这些结果突出了EGFR-AS1作为CRC诊断生物标志物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2104/9660029/274bbccc7e4f/jgo-13-05-2439-f1.jpg

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