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雷帕霉素作用机制靶点在接受活体肝移植的肿瘤簇阳性肝细胞癌患者包绕血管中的表达的临床意义

Clinical significance of mechanistic target of rapamycin expression in vessels that encapsulate tumor cluster-positive hepatocellular carcinoma patients who have undergone living donor liver transplantation.

作者信息

Toshida Katsuya, Itoh Shinji, Toshima Takeo, Yoshiya Shohei, Goto Ryoichi, Mita Atsuyoshi, Harada Noboru, Kohashi Kenichi, Oda Yoshinao, Yoshizumi Tomoharu

机构信息

Department of Surgery and Science, Graduate School of Medical Sciences Kyushu University Fukuoka Japan.

Department of Gastroenterological Surgery I Hokkaido University Graduate School of Medicine Sapporo Japan.

出版信息

Ann Gastroenterol Surg. 2023 Aug 28;8(1):163-171. doi: 10.1002/ags3.12735. eCollection 2024 Jan.

Abstract

BACKGROUND

There is limited published information regarding the expression of mechanistic target of rapamycin (mTOR) in vessels that encapsulate tumor cluster (VETC)-positive hepatocellular carcinoma (HCC). The mTOR inhibitor, everolimus, has been approved as an immunosuppressant for use in HCC patients after living donor liver transplantation (LDLT).

METHODS

Using a database of 214 patients who underwent LDLT for HCC, we examined the mTOR protein and angiopoietin-2 (Ang-2) in VETC-positive HCC by immunohistochemical staining. The presence of VETC and mTOR expression were evaluated in both primary and recurrent HCC lesions.

RESULTS

Forty-three of the 214 patients (20.1%) were VETC-positive, and 29 of these 43 patients (67.4%) expressed mTOR. Relative Ang-2 expression was significantly higher in the mTOR-positive than in the mTOR-negative group ( = 0.037). Thirty-four of the 214 patients experienced HCC recurrence after LDLT; 20 of these were operable. The primary lesions of six of these 20 patients were VETC-positive; five of these six patients also had VETC-positive recurrent lesions ( < 0.001). The expression of mTOR was significantly higher in the VETC-positive lesions ( = 0.0018).

CONCLUSIONS

We showed that mTOR expression was higher in the VETC-positive primary and recurrent lesions than in the VETC-negative ones.

摘要

背景

关于雷帕霉素作用靶点(mTOR)在包裹肿瘤簇的血管(VETC)阳性肝细胞癌(HCC)中的表达,已发表的信息有限。mTOR抑制剂依维莫司已被批准作为免疫抑制剂用于活体肝移植(LDLT)后的HCC患者。

方法

利用一个包含214例因HCC接受LDLT患者的数据库,我们通过免疫组化染色检测了VETC阳性HCC中的mTOR蛋白和血管生成素-2(Ang-2)。在原发性和复发性HCC病变中评估VETC的存在和mTOR表达。

结果

214例患者中有43例(20.1%)为VETC阳性,这43例患者中有29例(67.4%)表达mTOR。mTOR阳性组的相对Ang-2表达显著高于mTOR阴性组(=0.037)。214例患者中有34例在LDLT后发生HCC复发;其中20例可手术。这20例患者中有6例的原发性病变为VETC阳性;这6例患者中有5例的复发性病变也为VETC阳性(<0.001)。VETC阳性病变中的mTOR表达显著更高(=0.0018)。

结论

我们发现,VETC阳性的原发性和复发性病变中的mTOR表达高于VETC阴性病变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4374/10797838/65e1d1f9d04d/AGS3-8-163-g002.jpg

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