Serum KIAA1199 is an advanced-stage prognostic biomarker and metastatic oncogene in cholangiocarcinoma.
Serum KIAA1199 is an advanced-stage prognostic biomarker and metastatic oncogene in cholangiocarcinoma.
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DOI：
10.18632/aging.103964
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发表时间：
2020-11-10
期刊：
影响因子：
--
通讯作者：
Jin B
中科院分区：
文献类型：
--
作者：
Zhai X;Wang W;Ma Y;Zeng Y;Dou D;Fan H;Song J;Yu X;Xin D;Du G;Jiang Z;Zhang H;Zhang X;Jin B
背景：细胞增殖和迁移是恶性肿瘤进展的决定因素，更好地了解相关基因将有助于发现旨在防止癌症扩散的新靶点。有研究表明，KIAA1199 （CEMIP）是一种跨膜蛋白，在多种非癌细胞和癌细胞中表达。然而，KIAA1199在胆管癌（CCA）进展中的潜在作用尚不清楚。结果：癌症相关数据库分析显示KIAA1199在CCA中过表达。ELISA、免疫组化、Western blotting和qPCR均显示KIAA1199在血清、CCA组织和CCA细胞系中高表达。在血清（n = 41）和大样本验证（n = 177）队列中，较高的KIAA1199表达与较短的总生存期和无病生存期相关。在细胞水平上，KIAA1199过表达（OE）促进了CCA的生长和转移。皮下肿瘤异种移植实验表明KIAA1199促进CCA细胞增殖。此外，KIAA1199上调和沉默后，emt相关TGF-β通路组分的表达水平发生了显著变化。结论：KIAA1199是一种有前景的新型CCA诊断分子和治疗靶点。血清KIAA1199水平可作为预测CCA患者术后总体预后的一种有前景的临床工具。方法：从Gene Expression Omnibus （GEO）和the Cancer Genome Atlas （TCGA）数据库中下载cca相关的KIAA1199数据。为了评估KIAA1199对预后的影响，采用酶联免疫吸附试验（ELISA）测定41例手术切除患者的血清KIAA1199水平。采用免疫组化染色、Western blotting、qPCR等方法验证并回顾性回顾177例CCA患者癌组织标本中KIAA1199的表达水平。通过细胞功能测定和皮下肿瘤异种移植实验评估KIAA1199对CCA的影响。Western blotting检测上皮-间质转化（epithelial-mesenchymal transition， EMT）相关蛋白表达水平及相关信号通路激活。
Background: Cell proliferation and migration are the determinants of malignant tumor progression, and a better understanding of related genes will lead to the identification of new targets aimed at preventing the spread of cancer. Some studies have shown that KIAA1199 (CEMIP) is a transmembrane protein expressed in many types of noncancerous cells and cancer cells. However, the potential role of KIAA1199 in the progression of cholangiocarcinoma (CCA) remains unclear. Results: Analysis of cancer-related databases showed that KIAA1199 is overexpressed in CCA. ELISA, immunohistochemistry, Western blotting and qPCR indicated high expression levels of KIAA1199 in serum, CCA tissues and CCA cell lines. In the serum (n = 41) and large sample validation (n = 177) cohorts, higher KIAA1199 expression was associated with shorter overall survival and disease-free survival times. At the cellular level, KIAA1199 overexpression (OE) promoted CCA growth and metastasis. Subcutaneous tumor xenograft experiments showed that KIAA1199 enhances CCA cell proliferation. Additionally, the expression levels of components in the EMT-related TGF-β pathway changed significantly after KIAA1199 upregulation and silencing. Conclusion: KIAA1199 is a promising new diagnostic molecule and therapeutic target in CCA. The serum KIAA1199 level can be used as a promising clinical tool for predicting the overall postoperative outcomes of patients with CCA. Methods: CCA-related KIAA1199 data were downloaded from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. To assess the prognostic impact of KIAA1199, an enzyme-linked immunosorbent assay (ELISA) was used to measure the serum level of KIAA1199 in 41 patients who underwent surgical resection. Immunohistochemical staining, Western blotting and qPCR were used to verify and retrospectively review the expression levels of KIAA1199 in cancer tissue specimens from 177 CCA patients. The effect of KIAA1199 on CCA was evaluated by cell-based functional assays and subcutaneous tumor xenograft experiments. The expression levels of proteins associated with epithelial-mesenchymal transition (EMT) and activation of relevant signaling pathways were measured via Western blotting.
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影响因子：
7.3
作者：
Gonzalez DM;Medici D
通讯作者：
Medici D
影响因子：
3.7
作者：
Tiwari A;Schneider M;Fiorino A;Haider R;Okoniewski MJ;Roschitzki B;Uzozie A;Menigatti M;Jiricny J;Marra G
通讯作者：
Marra G
影响因子：
8.8
作者：
Nitta, T.;Mitsuhashi, T.;Hatanaka, Y.;Miyamoto, M.;Oba, K.;Tsuchikawa, T.;Suzuki, Y.;Hatanaka, K. C.;Hirano, S.;Matsuno, Y.
通讯作者：
Matsuno, Y.
影响因子：
8.8
作者：
Handra-Luca, A.;Hong, S-M;Walter, K.;Wolfgang, C.;Hruban, R.;Goggins, M.
通讯作者：
Goggins, M.
影响因子：
3.7
作者：
Matsuzaki, Shinji;Tanaka, Fumiaki;Mori, Masaki
通讯作者：
Mori, Masaki