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      High expression of HSP60 and survivin predicts poor prognosis for oral squamous cell carcinoma patients

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          Abstract

          Background

          HSP60 is a heat shock proteins (HSPs) family member and help mitochondrial protein to fold correctly. Survivin is one of the inhibitors of apoptosis protein family member, which plays a significant part in cancer progression. They were capable of forming HSP60-survivin complexes and involved in the development of various tumors.

          Methods

          The Cancer Genome Atlas (TCGA) database demonstrated that HSP60 and survivin and their correlation on mRNA expression level with OSCC patients. Besides, expression of HSP60 and survivin proteins was studied utilizing immunohistochemistry in tissue microarrays (TMA) in OSCC and in adjacent non-cancerous squamous epithelium (Non-CCSE) tissues.

          Results

          Significantly increased levels of HSP60 and survivin in most cancers compared to normal tissue by pan-cancer analysis. HSP60 and survivin proved a significantly increased expression in OSCC samples compared to Non-CCSE both on mRNA and protein (both P < 0.05). Additionally, elevated HSP60 displayed a positive correlation with survivin in terms of mRNA and protein expression levels (all P < 0.001). Patients with OSCC who had advanced clinical stage or lymph node metastasis (LNM) showed higher HSP60 expression ( P = 0.004, P = 0.006, respectively). Higher levels of the proteins HSP60 and survivin were significantly inversely correlated relationship with OSCC patients’ overall survival rates in multivariate survival analysis ( P = 0.018, P = 0.040). From the above results, overexpression of HSP60 and survivin protein may serve as independent biomarkers predicting poor prognosis in OSCC.

          Conclusions

          Elevated HSP60 and survivin might be served as novel poor prognosis biomarkers for surgically resected OSCC patients.

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          Most cited references29

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          Heat Shock Proteins and Cancer.

          Xiukun Lin, Shousong Cao, Jianming Wu … (2017)
          Heat shock proteins (HSPs) constitute a large family of proteins involved in protein folding and maturation whose expression is induced by heat shock or other stressors. The major groups are classified based on their molecular weights and include HSP27, HSP40, HSP60, HSP70, HSP90, and large HSPs. HSPs play a significant role in cellular proliferation, differentiation, and carcinogenesis. In this article we comprehensively review the roles of major HSPs in cancer biology and pharmacology. HSPs are thought to play significant roles in the molecular mechanisms leading to cancer development and metastasis. HSPs may also have potential clinical uses as biomarkers for cancer diagnosis, for assessing disease progression, or as therapeutic targets for cancer therapy.
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            Mitochondrial Stress Response and Cancer

            Jordan O’Malley, Rahul Kumar, Joseph R Inigo … (2020)
            Article 0 comments Cited 47 times – based on 0 reviews     Review now
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              Bitter melon derived extracellular vesicles enhance the therapeutic effects and reduce the drug resistance of 5-fluorouracil on oral squamous cell carcinoma

              Meng Yang, Qingqiong Luo, Xu Chen … (2021)
              Background Plant-derived extracellular vesicles (PDEVs) have been exploited for cancer treatment with several benefits. Bitter melon is cultivated as a vegetable and folk medicine with anticancer and anti-inflammatory activities. 5-Fluorouracil (5-FU) is widely used for cancer treatment. However, 5-FU-mediated NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammation activation induced the resistance of oral squamous cell carcinoma (OSCC) cells to 5-FU. In this study, we explored the potential of bitter melon-derived extracellular vesicles (BMEVs) for enhancing the therapeutic efficacy and reduce the resistance of OSCC to 5-FU. Results Herein, we demonstrate that bitter melon derived extracellular vesicles (BMEVs), in addition to their antitumor activity against OSCC have intrinsic anti-inflammatory functions. BMEVs induced S phase cell cycle arrest and apoptosis. Apoptosis induction was dependent on reactive oxygen species (ROS) production and JUN protein upregulation, since pretreatment with N -acetyl cysteine or catechin hydrate could prevent apoptosis and JUN accumulation, respectively. Surprisingly, BMEVs significantly downregulated NLRP3 expression, although ROS plays a central role in NLRP3 activation. We further assessed the underlying molecular mechanism and proposed that the RNAs of BMEVs, at least in part, mediate anti-inflammatory bioactivity. In our previous studies, NLRP3 activation contributed to the resistance of OSCC cells to 5-FU. Our data clearly indicate that BMEVs could exert a remarkable synergistic therapeutic effect of 5-FU against OSCC both in vitro and in vivo. Most notably, NLRP3 downregulation reduced the resistance of OSCC to 5-FU. Conclusions Together, our findings demonstrate a novel approach to enhance the therapeutic efficacy and reduce the drug resistance of cancer cells to chemotherapeutic agents, which provides proof-of-concept evidence for the future development of PDEVs-enhanced therapy. Graphic Abstract Supplementary Information The online version contains supplementary material available at 10.1186/s12951-021-00995-1.
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                Author and article information

                Contributors
                Qiuyuan Wen: wenqiuyuan@csu.edu.cn
                Journal
                Journal ID (nlm-ta): BMC Oral Health
                Journal ID (iso-abbrev): BMC Oral Health
                Title: BMC Oral Health
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1472-6831
                Publication date (Electronic): 3 September 2023
                Publication date PMC-release: 3 September 2023
                Publication date Collection: 2023
                Volume: 23
                Electronic Location Identifier: 629
                Affiliations
                [1 ]GRID grid.216417.7, ISNI 0000 0001 0379 7164, Department of Pathology, The Second Xiangya Hospital, , Central South University, ; Changsha, 410011 Hunan China
                [2 ]GRID grid.216417.7, ISNI 0000 0001 0379 7164, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, , Cancer Research Institute of Central South University, Central South University, ; Changsha, 410011 Hunan China
                Article
                Publisher ID: 3311
                DOI: 10.1186/s12903-023-03311-5
                PMC ID: 10476324
                PubMed ID: 37661276
                SO-VID: 0f01624e-7b34-4048-aabf-51ff3d9c15ef
                Copyright © © BioMed Central Ltd., part of Springer Nature 2023
                License:

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                Date received : 31 May 2023
                Date accepted : 14 August 2023
                Funding
                Funded by: Hunan Provincial Innovation Foundation for Postgraduate
                Award ID: grant No. CX20210373
                Funded by: the Fundamental Research Funds for the Central Universities of Central South University
                Award ID: grant No. 2021zzts1045
                Funded by: the National Natural Science Foundation of China
                Award ID: grant No. 82102805
                Award ID: grant No. 82272722
                Award ID: grant No. 81703009
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © BioMed Central Ltd., part of Springer Nature 2023

                ScienceOpen disciplines: Dentistry
                Keywords: oral squamous cell carcinoma,hsp60,survivin,prognosis,biomarker
                Data availability:
                ScienceOpen disciplines: Dentistry
                Keywords: oral squamous cell carcinoma, hsp60, survivin, prognosis, biomarker

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