Role of MEK1 and DIAPH3 expression in colorectal adenoma-carcinoma sequence.

Q3 Biochemistry, Genetics and Molecular Biology
Tumor Biology Pub Date : 2024-01-01 DOI:10.3233/TUB-230038
Abd AlRahman Mohammad Foda, Amira Kamal El-Hawary, Khaled Elnaghi, Wesal M Eldehna, Eman T Enan
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引用次数: 0

Abstract

Background: It is well established that most colorectal carcinomas arise from conventional adenomas through the adenoma-carcinoma sequence (ACS) model. mitogen-activated protein kinases (MAPKs) pathway has been reported as a crucial player in tumorigenesis. The MAPK signaling pathway is activated by different extracellular signals involving the "mitogen-activated/extracellular signal-regulated kinase 1 (MEK1)", and this induces the expression of genes involved in proliferation and cellular transformation. Diaphanous-related formin-3 (DIAPH3) acts as a potential metastasis regulator through inhibiting the cellular transition to amoeboid behavior in different cancer types.

Objective: The aim of the study was to investigate the pattern of immunohistochemical expression of MEK1 and DIAPH3 in colorectal adenoma (CRA) and corresponding colorectal carcinoma (CRC) specimens.

Methods: The immunohistochemical expression of DIAPH3 and MEK1 was examined in 43 cases of CRC and their associated adenomas using tissue microarray technique.

Results: MEK1 was overexpressed in 23 CRC cases (53.5%) and in 20 CRA cases (46.5%). DIAPH3 was overexpressed in 11 CRA cases (about 29%) which were significantly lower than CRC (22 cases; 58%) (P = 0.011). Both MEK1 and DIAPH3 overexpression were significantly correlated in CRC (P = 0.009) and CRA cases (P = 0.002). Tumors with MEK1 overexpression had a significantly higher tumor grade (P = 0.050) and perineural invasion (P = 0.017).

Conclusions: Both MEK1 and DIAPH3 are overexpressed across colorectal ACS with strong correlation between them. This co- expression suggests a possible synergistic effect of MEK1 and DIAPH-3 in colorectal ACS. Further large-scale studies are required to investigate the potential functional aspects of MEK1 and DIAPH3 in ACS and their involvement in tumor initiation and the metastatic process.

MEK1 和 DIAPH3 表达在结直肠腺瘤-癌序列中的作用
背景:据报道,丝裂原活化蛋白激酶(MAPKs)通路在肿瘤发生过程中起着至关重要的作用。MAPK 信号通路由涉及 "丝裂原活化/细胞外信号调节激酶 1(MEK1)"的不同细胞外信号激活,从而诱导参与增殖和细胞转化的基因的表达。Diaphanous相关甲形蛋白-3(DIAPH3)通过抑制不同癌症类型的细胞向变形行为转变,成为潜在的转移调节因子:目的:研究结直肠腺瘤(CRA)和相应的结直肠癌(CRC)标本中 MEK1 和 DIAPH3 的免疫组化表达模式:方法:采用组织芯片技术检测43例CRC及其相关腺瘤中DIAPH3和MEK1的免疫组化表达:结果:MEK1在23例CRC(53.5%)和20例CRA(46.5%)中过表达。11 例 CRA(约 29%)中 DIAPH3 过表达,明显低于 CRC(22 例;58%)(P = 0.011)。在 CRC(P = 0.009)和 CRA(P = 0.002)病例中,MEK1 和 DIAPH3 的过表达均有显著相关性。MEK1过表达的肿瘤分级(P = 0.050)和神经周围浸润(P = 0.017)明显更高:结论:MEK1和DIAPH3在结直肠癌ACS中均有过表达,且两者之间有很强的相关性。这种共同表达表明,MEK1 和 DIAPH-3 在结直肠 ACS 中可能存在协同作用。需要进一步开展大规模研究,以探讨 MEK1 和 DIAPH3 在 ACS 中的潜在功能方面,以及它们在肿瘤发生和转移过程中的参与情况。
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来源期刊
Tumor Biology
Tumor Biology 医学-肿瘤学
CiteScore
5.40
自引率
0.00%
发文量
18
审稿时长
1 months
期刊介绍: Tumor Biology is a peer reviewed, international journal providing an open access forum for experimental and clinical cancer research. Tumor Biology covers all aspects of tumor markers, molecular biomarkers, tumor targeting, and mechanisms of tumor development and progression. Specific topics of interest include, but are not limited to: Pathway analyses, Non-coding RNAs, Circulating tumor cells, Liquid biopsies, Exosomes, Epigenetics, Cancer stem cells, Tumor immunology and immunotherapy, Tumor microenvironment, Targeted therapies, Therapy resistance Cancer genetics, Cancer risk screening. Studies in other areas of basic, clinical and translational cancer research are also considered in order to promote connections and discoveries across different disciplines. The journal publishes original articles, reviews, commentaries and guidelines on tumor marker use. All submissions are subject to rigorous peer review and are selected on the basis of whether the research is sound and deserves publication. Tumor Biology is the Official Journal of the International Society of Oncology and BioMarkers (ISOBM).
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