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SH3PXD2B(Tks4)在人肝细胞癌中的预后价值:一项联合多组学和实验研究。

Prognostic value of SH3PXD2B (Tks4) in human hepatocellular carcinoma: a combined multi-omics and experimental study.

机构信息

Department of Pathology, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, China.

Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, China.

出版信息

BMC Med Genomics. 2021 Apr 28;14(1):115. doi: 10.1186/s12920-021-00963-6.

DOI:10.1186/s12920-021-00963-6
PMID:33906640
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8080318/
Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is one of the most common and fatal cancers worldwide. HCC invasion and metastasis are crucial for its poor prognosis. SH3PXD2B is a scaffold protein and critical for intravascular and extravascular invasion and metastasis of various types of tumors. However, the role of SH3PXD2B in HCC progression remains unclear.

METHODS

The levels of SH3PXD2B mRNA transcripts in the TCGA database and SH3PXD2B protein expression in the Human Protein Atlas were analyzed. Furthermore, the levels of SH3PXD2B expression in clinical samples were analyzed by quantitative RT-PCR and immunohistochemistry. The potential association of the levels of SH3PXD2B expression with clinicopathological characteristics, overall survival (OS), and recurrence-free survival (RFS) of HCC patients was analyzed. The impact of SH3PXD2B silencing by shRNA-based lentivirus transduction on the proliferation and invasion of human HCC Hep3B and Huh7 cells was determined.

RESULTS

SH3PXD2B expression was up-regulated in HCC tissues in the TCGA and Human Protein Atlas as well as clinical samples, relative to that of non-tumor liver samples. The levels of SH3PXD2B expression in HCC tissues were significantly associated with higher HBV infection rate, higher HCC grades and TNM stages, higher Ki-67 expression, higher serum α-fetoprotein (AFP), a shorter OS and RFS of HCC patients. Functionally, SH3PXD2B silencing significantly inhibited the formation and function of invadopodia and the invasion of Hep3B and Huh7 cells, but did not affect their proliferation in vitro.

CONCLUSIONS

Our data suggest that SH3PXD2B may promote the invasion and metastasis of HCC and be a valuable therapeutic target and biomarker for treatment and prognosis of HCC.

摘要

背景

肝细胞癌(HCC)是全球最常见和致命的癌症之一。HCC 的侵袭和转移对其预后不良至关重要。SH3PXD2B 是一种支架蛋白,对各种类型肿瘤的血管内和血管外侵袭和转移至关重要。然而,SH3PXD2B 在 HCC 进展中的作用尚不清楚。

方法

分析 TCGA 数据库中 SH3PXD2B mRNA 转录本的水平和人类蛋白质图谱中 SH3PXD2B 蛋白的表达。此外,通过定量 RT-PCR 和免疫组织化学分析临床样本中 SH3PXD2B 表达水平。分析 SH3PXD2B 表达水平与 HCC 患者临床病理特征、总生存期(OS)和无复发生存期(RFS)的潜在相关性。通过基于 shRNA 的慢病毒转导沉默 SH3PXD2B 对人 HCC Hep3B 和 Huh7 细胞增殖和侵袭的影响。

结果

TCGA 和人类蛋白质图谱以及临床样本中 HCC 组织中 SH3PXD2B 的表达上调,与非肿瘤肝组织样本相比。HCC 组织中 SH3PXD2B 表达水平与 HBV 感染率较高、HCC 分级和 TNM 分期较高、Ki-67 表达较高、血清 α-胎蛋白(AFP)较高、HCC 患者 OS 和 RFS 较短显著相关。功能上,沉默 SH3PXD2B 显著抑制了 Hep3B 和 Huh7 细胞侵袭小窝的形成和功能以及侵袭能力,但不影响其体外增殖。

结论

我们的数据表明,SH3PXD2B 可能促进 HCC 的侵袭和转移,是 HCC 治疗和预后的有价值的治疗靶点和生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afd9/8080318/40384e232911/12920_2021_963_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afd9/8080318/b3b7445bd820/12920_2021_963_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afd9/8080318/80ba45d4b08a/12920_2021_963_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afd9/8080318/40384e232911/12920_2021_963_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afd9/8080318/b3b7445bd820/12920_2021_963_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afd9/8080318/80ba45d4b08a/12920_2021_963_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afd9/8080318/40384e232911/12920_2021_963_Fig3_HTML.jpg

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