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中国结直肠癌患者术前甲基化 septin 9 的临床价值。

Clinical value of preoperative methylated septin 9 in Chinese colorectal cancer patients.

机构信息

Department of Pharmacy, Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.

Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.

出版信息

World J Gastroenterol. 2019 May 7;25(17):2099-2109. doi: 10.3748/wjg.v25.i17.2099.

Abstract

BACKGROUND

The methylated septin 9 (mSEPT9) assay was the first blood-based test approved by the United States Food and Drug Administration as a colorectal screening test. However, the diagnostic and prognostic role of preoperative mSEPT9 for colorectal cancer (CRC) in Chinese patients is still unknown.

AIM

To improve the understanding of diagnostic and prognostic factors, serum mSEPT9 was detected in Chinese CRC patients.

METHODS

A retrospective analysis of 354 cases, of which 300 had CRC and 54 were normal, was performed in China. Patients' characteristics, treatments, and laboratory data, including age, the date of surgery, Union for International Cancer Control (UICC) stages, distant metastasis (M), and so on, were collected. Methylation levels of SEPT9 were quantified by quantitative, methylation-specific polymerase chain reaction before surgery. In addition, the effects of mSEPT9 on the occurrence and prognosis of 330 CRC cases from The Cancer Genome Atlas (TCGA) database were evaluated using bioinformatics analyses. Potential prognostic factors for overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier univariate analysis.

RESULTS

In Chinese CRC patients, positive mSEPT9 was strongly associated with advanced UICC stages, deeper invasion by the primary tumor, and more distant metastasis. Methylation levels of SEPT9 were stage-dependent and showed a stepwise increase in UICC stages (I-IV), primary tumor categories (T1-T4), regional node categories (N0-N2), and distant metastasis categories (M0-M1). The patients with positive mSEPT9 showed a tendency toward lower PFS. After analyzing TCGA clinical data, the high mSEPT9 group was found to be obviously correlated only with more distant metastasis. The patients with high mSEPT9 levels showed a tendency toward lower OS. Besides, nine meaningful mSEPT9 sites were found to provide guidance for the follow-up studies.

CONCLUSION

MSEPT9 analysis may add valuable information to current tumor staging. Serum mSEPT9 in Chinese CRC patients appears to offer promising novel prognostic markers and might be considered for monitoring CRC recurrence.

摘要

背景

甲基化 Septin9(mSEPT9)检测是首个获得美国食品药品监督管理局批准的用于结直肠癌(CRC)筛查的基于血液的检测方法。然而,术前 mSEPT9 对中国 CRC 患者的诊断和预后作用仍不清楚。

目的

为了更好地了解诊断和预后因素,本研究在中国 CRC 患者中检测了血清 mSEPT9。

方法

在中国进行了一项回顾性分析,共纳入 354 例患者,其中 300 例为 CRC 患者,54 例为正常对照。收集了患者的特征、治疗和实验室数据,包括年龄、手术日期、国际抗癌联盟(UICC)分期、远处转移(M)等。术前通过定量甲基化特异性聚合酶链反应检测 SEPT9 的甲基化水平。此外,还通过生物信息学分析评估了 mSEPT9 对来自癌症基因组图谱(TCGA)数据库的 330 例 CRC 病例的发生和预后的影响。通过 Kaplan-Meier 单因素分析评估了总生存期(OS)和无进展生存期(PFS)的潜在预后因素。

结果

在中国 CRC 患者中,mSEPT9 阳性与较晚的 UICC 分期、原发肿瘤侵袭深度更深和远处转移更广泛密切相关。SEPT9 的甲基化水平与 UICC 分期(I-IV)、原发肿瘤分类(T1-T4)、区域淋巴结分类(N0-N2)和远处转移分类(M0-M1)呈阶段依赖性增加。mSEPT9 阳性的患者倾向于 PFS 较低。对 TCGA 临床数据进行分析后发现,高 mSEPT9 组仅与远处转移更为相关。高 mSEPT9 水平的患者 OS 较低。此外,还发现了 9 个有意义的 mSEPT9 位点,为后续研究提供了指导。

结论

mSEPT9 分析可能为当前的肿瘤分期提供有价值的信息。中国 CRC 患者的血清 mSEPT9 似乎提供了有前途的新型预后标志物,并可能被考虑用于监测 CRC 复发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c9/6506579/ad44b863678c/WJG-25-2099-g001.jpg

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