Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Apr 28;14(1):115.
doi: 10.1186/s12920-021-00963-6.

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

Xiang Kui #  1 , Yan Wang #  1 , Cheng Zhang #  2   3 , Hai Li #  4 , Qingfeng Li #  1 , Yang Ke  5 , Lin Wang  6
Affiliations

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

Xiang Kui et al. BMC Med Genomics. .

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.

Keywords: Clinicopathology; Hepatocellular carcinoma; Human Protein Atlas; Invasion; Omics; Proliferation; Recurrence; SH3PXD2B; Survival; TCGA.

PubMed Disclaimer

Conflict of interest statement

The authors declare that there is no conflict of interest regarding the publication of this manuscript.

Figures

Fig. 1
Fig. 1
SH3PXD2B expression is up-regulated in HCC tissues. The levels of SH3PXD2B mRNA transcripts and protein expression in HCC tissues of the TCGA database (a) and the Human Protein Atlas (b) were analyzed. c The relative levels of SH3PXD2B mRNA transcripts in 24 pairs of freshly surgical HCC and paired non-tumor liver tissues were analyzed by qRT-PCR. d Immunohistochemical analysis of 89 pairs of HCC and non-tumor liver samples. Data are representative images (magnification × 200) or expressed as the mean values in individual samples or mean ± SD of each group
Fig. 2
Fig. 2
Higher levels of SH3PXD2B expression are associated with shorter survival periods of HCC patients. a, b All HCC patients were stratified, according to their TNM stages or pathological grades and the levels of SH3PXD2B mRNA transcripts were analyzed. Data are shown as the box and whisker plot, and the lines indicate the means of each group. c, d HCC patients were stratified, according to the median value of SH3PXD2B mRNA transcripts and their overall survival (OS) and recurrence-free survival (RFS) were analyzed by the Kaplan–Meier method and the log-rank test. e, f The OS and RFS of 89 HCC patients were analyzed after stratification of them into higher and lower SH3PXD2B expression with the least P value of OS, determined using the X-Tile software
Fig. 3
Fig. 3
SH3PXD2B silencing inhibits the invasion, but not proliferation of Hep3B and Huh7 cells. Hep3B and Huh7 cells were transduced with lentivirus for expression of SH3PXD2B-specific shRNA or control shRNA (Scr). The relative levels of SH3PXD2B to the control β-tubulin protein expression in different groups of Hep3B (a, b) and Huh7 (c, d) cells were determined by Western blot. e The dynamic proliferation of Hep3B and Huh7 cells was determined at the indicated time points. f, g The invasion of different groups of Hep3B and Huh7 cells was examined by transwell invasion assays. h–j The formation of invadopodia in different groups of Hep3B and Huh7 cells was examined by immunofluorescence assays. k–m The function of invadopodia in different groups of Hep3B and Huh7 cells was examined by in situ zymography. A total of 150 cells per group were analyzed by two researchers in a blinded manner. Data are representative images or expressed as the mean ± SD of each group from three separate experiments. Bar scale in F = 100 μm. Bar scales in H and K = 20 μm
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, Znaor A, Bray F. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144(8):1941–1953. doi: 10.1002/ijc.31937. - DOI - PubMed
    1. Villanueva A. Hepatocellular carcinoma. N Engl J Med. 2019;380(15):1450–1462. doi: 10.1056/NEJMra1713263. - DOI - PubMed
    1. Ke Y, Wu T, Lei X, Zhang C, Zhou J, Li J, Zhang H, Chen X, Wang J, Wang L. Reduced glutathione ameliorates liver function, oxidative stress and inflammation after interventional therapy for hepatocellular carcinoma. J BUON. 2020;25(3):1361–1367. - PubMed
    1. Ke Y, Zhong J, Guo Z, Liang Y, Li L, Xiang B. Comparison liver resection with transarterial chemoembolization for Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma patients on long-term survival after SPSS propensity score matching. Zhonghua Yi Xue Za Zhi. 2014;94(10):747–750. - PubMed
    1. Zhou J, Ke Y, Lei X, Wu T, Li Y, Bao T, Tang H, Zhang C, Wu X, Wang G, et al. Meta-analysis: the efficacy of metformin and other anti-hyperglycemic agents in prolonging the survival of hepatocellular carcinoma patients with type 2 diabetes. Ann Hepatol. 2020;19(3):320–328. doi: 10.1016/j.aohep.2019.11.008. - DOI - PubMed

MeSH terms

Substances