LASP-1在进展期腺瘤及癌变过程中诊断价值和分子机制研究

承德医学院学报 ›› 2024, Vol. 41 ›› Issue (1): 1-4.

• 基础医学 • 下一篇

LASP-1在进展期腺瘤及癌变过程中诊断价值和分子机制研究

付娟娟¹, 李思锦², 周龙妹², 李骏杰³, 李萍², 何培元², 侯志平^1,*

1.承德医学院基础医学院,河北承德 067000;
2.承德医学院附属医院;
3.承德医学院中医学院

收稿日期:2023-04-25 出版日期:2024-02-10 发布日期:2024-03-05
通讯作者: *
基金资助:
河北省人才工程培养资助项目（A01902016）; 河北省科学技术厅重点研发项目：卫生健康创新专项（21377791D）; 河北省高等学校科学技术研究项目（ZD2022124）

Diagnostic Value and Molecular Mechanism of LASP-1 in the Process of Advanced Adenoma and Carcinogenesis

FU Juan-juan¹, LI Si-jin², ZHOU Long-mei², LI Jun-jie³, LI Ping², HE Pei-yuan², HOU Zhi-ping^1,*

1. School of Basic Medicine, Chengde Medical University, Chengde, Hebei, 067000, China;
2. The Affiliated Hospital of Chengde Medical University;
3. College of Traditional Chinese Medicine, Chengde Medical University

Received:2023-04-25 Online:2024-02-10 Published:2024-03-05

摘要/Abstract

摘要： 目的检测LASP-1在进展期腺瘤及腺癌的表达水平及其诊断价值,探讨进展期腺瘤癌变的分子机制。方法收集48例结直肠腺癌（CRC组)、13例腺瘤（CRA组）患者以及22例健康志愿者（Normal组）的血浆标本,酶联免疫吸附试验（ELISA）检测血浆样本LASP-1的表达水平;全自动化化学发光免疫分析法检测血浆CEA的表达情况。通过ROC曲线下面积评估血浆LASP-1、CEA及二者联合检测CRC及CRA的诊断效能;Spearman相关分析血浆LASP-1与临床病理特征的关系。在TCGA数据库中检测LASP-1在CRC I-Ⅳ期患者与Normal组的表达情况;在GEO数据库检测LASP-1在CRC与CRA组患者的差异表达。免疫组织化学法、人类蛋白免疫组化数据库分别检测P53、LASP-1在CRC患者组织中的表达情况。结果 ELISA结果显示CRC、CRA组患者血浆LASP-1浓度均明显高于Normal组（P<0.01）,而CRC、CRA和Normal组患者CEA表达水平无明显统计学意义。ROC曲线分析表明血浆LASP-1在诊断CRC、CRA时敏感性及特异性均高于CEA,二者联合检测CRC、CRA时,曲线下面积(AUC)分别达到0.982、0.99。TCGA数据库结果显示LASP-1在CRC各期患者组织中的表达水平明显高于Normal组（P<0.05）,GEO数据库结果显示LASP-1在CRC组中的表达明显高于CRA组（P<0.05）。免疫组化结果显示突变型P53占CRC组64.5%。人类蛋白免疫组化数据库显示与正常肠上皮组织比较,LASP-1在CRC组织中呈高表达。结论 LASP-1联合CEA是CRC、CRA患者早期诊断的潜在诊断指标;LASP-1可能参与腺瘤癌变分子机制,使CRC在腺瘤期发现并进行干预治疗成为可能。

关键词: LASP-1, 进展期腺瘤, 结直肠腺癌, P53

Abstract: Objective To detect the expression level of LASP-1 in advanced adenoma and adenocarcinoma and its diagnostic value, and to explore the molecular mechanism of malignant transformation of advanced adenoma. Methods Plasma samples were collected from 48 patients with colorectal adenocarcinoma (CRC group), 13 patients with adenoma (CRA group) and 22 healthy volunteers (Normal group). The expression level of LASP-1 in plasma samples was detected by enzyme-linked immunosorbent assay (ELISA). The expression of CEA in plasma was detected by automatic chemiluminescence immunoassay. The diagnostic efficacy of plasma LASP-1, CEA and their combination in CRC and CRA was evaluated by the area under the ROC curve. Spearman correlation analysis was used to analyze the relationship between plasma LASP-1 and clinicopathological features. The expression of LASP-1 in CRC stage I-IV patients and Normal group was detected in TCGA database. Next, the differential expression of LASP-1 in CRC and CRA groups was detected in GEO database. Immunohistochemical method and human protein immunohistochemistry database were used to detect the expression of P53 and LASP-1 in CRC tissues. Results ELISA results showed that the plasma concentrations of LASP-1 in CRC and CRA groups were significantly higher than those in Normal group (P<0.01), while there was no significant difference in CEA expression levels among CRC, CRA and Normal groups. ROC curve analysis showed that the sensitivity and specificity of plasma LASP-1 in the diagnosis of CRC and CRA were higher than those of CEA. When the two were combined, the area under the curve (AUC) was 0.982 and 0.99, respectively. TCGA database results showed that the expression level of LASP-1 in the tissues of CRC patients in each stage was significantly higher than that in the Normal group (P<0.05). GEO database results showed that the expression level of LASP-1 in the CRC group was significantly higher than that in the CRA group (P<0.05). Immunohistochemical results showed that mutant P53 accounted for 64.5% of the CRC group. Human protein immunohistochemistry database showed that LASP-1 was highly expressed in CRC tissues compared with normal intestinal epithelial tissues. Conclusion LASP-1 combined with CEA is a potential diagnostic indicator for early diagnosis of CRC and CRA patients; LASP-1 may be involved in the molecular mechanism of adenomasis cancer, making it possible for CRC to be detected and intervened in the adenoma stage.

Key words: LASP-1, progressive adenoma, colorectal adenocarcinoma, P53

中图分类号:

R735.3

付娟娟, 李思锦, 周龙妹, 李骏杰, 李萍, 何培元, 侯志平. LASP-1在进展期腺瘤及癌变过程中诊断价值和分子机制研究[J]. 承德医学院学报, 2024, 41(1): 1-4.

FU Juan-juan, LI Si-jin, ZHOU Long-mei, LI Jun-jie, LI Ping, HE Pei-yuan, HOU Zhi-ping. Diagnostic Value and Molecular Mechanism of LASP-1 in the Process of Advanced Adenoma and Carcinogenesis[J]. Journal of Chengde Medical University, 2024, 41(1): 1-4.

参考文献

[1] Bray F, Ferlay J, Soerjomataram I, et al.Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424.
[2] Hu Z, Ding J, Ma Z, et al.Quantitative evidence for early metastatic seeding in colorectal cancer[J]. Nat Genet, 2019. 51(7): 1113-1122.
[3] Miller KD, Nogueira L, Mariotto AB, et al.Cancer treatment and survivorship statistics, 2019[J]. CA Cancer J Clin, 2019, 69(5): 363-385.
[4] Li YD, Jiang XZ, Geng ZW, et al.Value of combined detection of serum CEA, AFP and CA19-9 in diagnosis of colorectal cancer[J]. Medical & Pharmaceutical Journal of Chinese People's Liberation Army, 2015, 27(5): 53-55.
[5] Zhao L, Ding YQ.Impact of LASP-1 expression on proli-feration antumorigenesis of human colorectal cancer cell line SW480[J]. Chinese Journal of Pathology, 2010, 39(12): 830-834.
[6] Ryan KM, Phillips AC, Vousden KH.Regulation and function of the p53 tumor suppressor protein[J]. Curr Opin Cell Biol, 2001, 13: 332-337.
[7] 顾晋,汪建平,孙燕,等. 中国结直肠癌诊疗规范(2017 年版)[J]. 中华临床医师杂志,2018,12(1):3-23.
[8] Choong MK, Tsafnat G.Genetic and epigenetic biomarkers of colorectal cancer[J]. Clin Gastroenterol Hepatol, 2012, 10(1): 9-15.
[9] Rasmussen L, Nielsen HJ, Christensen IJ.Early Detection and Recurrence of Colorectal Adenomas by Combination of Eight Cancer-Associated Biomarkers in Plasma[J]. Clin Exp Gastroenterol, 2020, 13: 273-284.
[10] Panaviene Z, Moncman CL.Linker region of nebulin family members plays an important role in targeting these molecules to cellular structures[J]. Cell Tissue Res, 2007, 327(2): 353-369.
[11] Fujita Y, Chokki T, Nishioka T, et al.The emergence of nebulin repeats and evolution of lasp family proteins[J]. Cytoskeleton (Hoboken), 2021, 78(9): 419-435.
[12] Zhou D, Yang L, Zheng L, et al.Exome capture sequencing of adenoma reveals genetic alterations in multiple cellular pathways at the early stage of colorectal tumorigenesis[J]. PLoS One, 2013, 8(1): e53310.
[13] Vogelstein B, Fearon ER, Hamilton SR, et al.Genetic alterations during colorectal-tumor development. N Engl J Med, 1988, 319(9): 525-532.
[14] Lin SH, Raju GS, Huff C, et al.The somatic mutation landscape of premalignant colorectal adenoma[J]. Gut, 2018, 67(7): 1299-1305.
[15] Wang B, Feng P, Xiao Z, et al.LIM and SH3 protein 1 (Lasp1) is a novel p53 transcriptional target involved in hepatocellular carcinoma[J]. J Hepatol, 2009, 50(3): 528-537.

LASP-1在进展期腺瘤及癌变过程中诊断价值和分子机制研究

Diagnostic Value and Molecular Mechanism of LASP-1 in the Process of Advanced Adenoma and Carcinogenesis

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