Low levels of tumor suppressor candidate 3 predict poor prognosis of patients with hepatocellular carcinoma

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Low levels of tumor suppressor candidate 3 predict poor prognosis of patients with hepatocellular carcinoma

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Author(s): Xu-Ren Sheng ¹ ^, ² , Song-Ge Xing ² ^, ³ , Run-Dong Wang ² , Kang Chen ² , Wei-Dong Jia ¹ ^, ²

Publication date (Electronic): 21 February 2018

Journal: OncoTargets and therapy

Publisher: Dove Medical Press

Keywords: TUSC3, hepatocellular carcinoma, prognosis, immunohistochemistry, overall survival

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Abstract

Purpose

The tumor suppressor candidate 3 ( TUSC3) has been considered to be closely associated with the occurrence, development and invasion of various malignant tumors. However, the expression of TUSC3 in hepatocellular carcinoma (HCC) tissues remains ambiguous. The purpose of this research was to investigate the expression of TUSC3 in HCC tissues and analyze the relationship between TUSC3 levels and clinicopathological characteristics and prognosis of HCC patients.

Materials and methods

Immunohistochemistry was used to detect the expression of TUSC3 in HCC and the corresponding para-cancerous tissues from 92 samples of HCC patients. mRNA and protein expression levels of TUSC3 were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays in 25 paired HCC and corresponding adjacent nontumor tissues. Furthermore, statistical analysis was applied to evaluate the correlation between TUSC3 level and the clinicopathological features and prognosis of HCC patients.

Results

Immunohistochemical assay indicated that the expression of TUSC3 was significantly lower in HCC tissues when compared with the corresponding para-cancerous tissues ( χ ²=11.512, P=0.001). The analysis of clinicopathological characteristics showed that low expression of TUSC3 in HCC tissues was significantly associated with Edmondson grade, Barcelona Clinic Liver Cancer stage and tumor size ( P=0.008, 0.009 and 0.020, respectively). Univariate analysis showed that the expression of TUSC3 was strongly correlated with overall survival (OS) and disease-free survival (DFS) after radical surgery in HCC patients ( P<0.001, P<0.001, respectively). Multivariate analysis revealed that the TUSC3 level was an independent risk factor for OS and DFS in HCC patients ( P=0.001, P<0.001, respectively). Results of qRT-PCR and Western blot assays indicated that the level of TUSC3 in HCC tissues was significantly lower than that in the corresponding adjacent noncancerous tissues ( P<0.01, P<0.001).

Conclusion

The expression of TUSC3 in HCC was significantly downregulated and was correlated with tumor progression and prognosis, which could be used as an independent predictor of prognosis in HCC patients.

Most cited references 23

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Intracellular functions of N-linked glycans.

A. Helenius, M. Aebi (2001)

N-linked oligosaccharides arise when blocks of 14 sugars are added cotranslationally to newly synthesized polypeptides in the endoplasmic reticulum (ER). These glycans are then subjected to extensive modification as the glycoproteins mature and move through the ER via the Golgi complex to their final destinations inside and outside the cell. In the ER and in the early secretory pathway, where the repertoire of oligosaccharide structures is still rather small, the glycans play a pivotal role in protein folding, oligomerization, quality control, sorting, and transport. They are used as universal "tags" that allow specific lectins and modifying enzymes to establish order among the diversity of maturing glycoproteins. In the Golgi complex, the glycans acquire more complex structures and a new set of functions. The division of synthesis and processing between the ER and the Golgi complex represents an evolutionary adaptation that allows efficient exploitation of the potential of oligosaccharides.

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Current strategy for staging and treatment: the BCLC update and future prospects.

Alejandro Forner, María E Reig, Carlos Rodriguez de Lope … (2010)

Staging and treatment indication are relevant topics in the management of patients with hepatocellular carcinoma (HCC) and for optimal results, they have to take into account liver function, tumor stage, and physical status. For any staging system to be meaningful it has to link staging with treatment indication; this should be based on robust scientific data. Currently, the sole proposal that serves both aims is the Barcelona Clinic Liver Cancer (BCLC) approach. It takes into account the relevant parameters of all important dimensions and divides patients into very early/early, intermediate, advanced, and end-stage. Early-stage HCC patients should be considered for potentially curative options such as resection, ablation, and transplantation. Patients at intermediate stage benefit from chemoembolization, whereas patients at an advanced stage, or who cannot benefit from options of higher priority, have sorafenib as the standard treatment. Finally, patients at end-stage should merely receive palliative care.

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Hepatocellular carcinoma: current management and perspectives for the future.

Jürgen Weitz, Moritz Koch, Nuh N. Rahbari … (2011)

To review the literature on current management of hepatocellular carcinoma (HCC). Hepatocellular carcinoma represents one of the most common malignancies worldwide with a rising incidence in western countries. There have been substantial advances in the surgical and medical treatment of HCC within the past 2 decades. A literature review was performed in the MEDLINE database to identify studies on the management of HCC. On the basis of the available evidence recommendations for practice were graded using the Oxford Centre for Evidence-based Medicine classification. Advances in surgical technique and perioperative care have established surgical resection and orthotopic liver transplantation (OLT) as primary curative therapy for HCC in noncirrhotic and cirrhotic patients, respectively. Primary resection and salvage OLT may be indicated in cirrhotics with preserved liver function. Selection criteria for OLT remain debated, as slight expansion of the Milan criteria may not worsen prognosis but is limited by organ shortage and prolonged waiting time with less favorable outcome on intention-to-treat analyses. Strategies of neoadjuvant treatment before OLT require evaluation within prospective trials. Transarterial chemoembolization is the primary therapy in patients with inoperable HCC and compensated liver function. Although systemic chemotherapy is not effective in patients with advanced HCC, there is recent evidence that these patients benefit from new molecular targeted therapies. If these agents are also effective in the neoadjuvant and adjuvant setting is currently being investigated. Furthermore, selective intra-arterial radiation therapy represents a promising new approach for treatment of unresectable HCC. Recent developments in the surgical and medical therapy have significantly improved outcome of patients with operable and advanced HCC. A multidisciplinary approach seems essential to further improve patients' prognosis.

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Author and article information

Journal

Journal ID (nlm-ta): Onco Targets Ther

Journal ID (iso-abbrev): Onco Targets Ther

Journal ID (publisher-id): OncoTargets and Therapy

Title: OncoTargets and therapy

Publisher: Dove Medical Press

ISSN (Electronic): 1178-6930

Publication date Collection: 2018

Publication date (Electronic): 21 February 2018

Volume: 11

Pages: 909-917

Affiliations

[1 ]Department of Liver Surgery, Affiliated Provincial Hospital, Anhui Medical University

[2 ]Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery

[3 ]CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science and Technology of China, Hefei, People’s Republic of China

Author notes

Correspondence: Wei-Dong Jia, Department of General Surgery, Affiliated Provincial Hospital, Anhui Medical University, 17 Lujiang Road, Luyang, Hefei, Anhui 230001, People’s Republic of China, Tel/fax +86 0551 6228 3740, Email jwd1968@ 123456sina.com

[*]

These authors contributed equally to this work

Article

Publisher ID: ott-11-909

DOI: 10.2147/OTT.S153381

PMC ID: 5825997

SO-VID: a38b9330-2d2e-4c75-8791-e5e058943acd

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The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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Low levels of tumor suppressor candidate 3 predict poor prognosis of patients with hepatocellular carcinoma

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Abstract

Purpose

Materials and methods

Results

Conclusion

Most cited references 23

Intracellular functions of N-linked glycans.

Current strategy for staging and treatment: the BCLC update and future prospects.

Hepatocellular carcinoma: current management and perspectives for the future.

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