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de Azevedo ALK, Gomig THB, Ribeiro EMDSF. Stress-induced phosphoprotein 1: how does this co-chaperone influence the metastasis steps? Clin Exp Metastasis 2024; 41:589-597. [PMID: 38581620 DOI: 10.1007/s10585-024-10282-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 02/27/2024] [Indexed: 04/08/2024]
Abstract
In several cancer types, metastasis is associated with poor prognosis, survival, and quality of life, representing a life risk more significant than the primary tumor itself. Metastasis is a multi-step process that spreads tumor cells from primary sites to surrounding or distant organs, originating secondary tumors. The interconnected steps that drive metastasis depend of several capabilities that enable cells to detach from the primary tumor, acquire motility and migrate through the basal membrane; invade and spread through the vascular system, and finally settle and originate a new tumor. Recently, stress-induced phosphoprotein 1 (STIP1) has emerged as a protein capable of driving tumor cells through these metastasis steps by mediating several biological processes and signaling pathways. This protein is mainly known for its function as a co-chaperone, acting as a scaffold for the interaction of its client heat-shock proteins Hsp70/90 chaperones; however, it is also known that STIP1 can act independently of chaperones to activate downstream phosphorylation pathways. The over-expression of STIP1 has been reported across various cancer types, identifying it as a potential biomarker for predicting patient prognosis and monitoring the progression of metastasis. Here, we present a discussion on how this co-chaperone mediates the initial steps of metastasis (cell adhesion loss, epithelial-to-mesenchymal transition, and angiogenesis), highlighting the biological mechanisms in which STIP1 plays a vital role, also presenting an overview of the current knowledge regarding its clinical relevance.
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Affiliation(s)
- Alexandre Luiz Korte de Azevedo
- Genetics Post-Graduation Program, Genetics Department, Federal University of Paraná, P.O. box 19071, Curitiba, Paraná, CEP: 81531-990, Brazil
| | - Talita Helen Bombardelli Gomig
- Genetics Post-Graduation Program, Genetics Department, Federal University of Paraná, P.O. box 19071, Curitiba, Paraná, CEP: 81531-990, Brazil
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Dourado MR, Elseragy A, da Costa BC, Téo FH, Guimarães GN, Machado RA, Risteli M, Wahbi W, Gurgel Rocha CA, Paranaíba LMR, González-Arriagada WA, da Silva SD, Rangel ALCA, Marques MR, Rossa Junior C, Salo T, Coletta RD. Stress induced phosphoprotein 1 overexpression controls proliferation, migration and invasion and is associated with poor survival in oral squamous cell carcinoma. Front Oncol 2023; 12:1085917. [PMID: 36713524 PMCID: PMC9874128 DOI: 10.3389/fonc.2022.1085917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 12/22/2022] [Indexed: 01/12/2023] Open
Abstract
Objective Although there have been remarkable achievements in the molecular landscape of oral squamous cell carcinoma (OSCC) in recent years, bringing advances in the understanding of its pathogenesis, development and progression, little has been applied in the prognosis and choosing the optimal treatment. In this study, we explored the influence of the stress induced phosphoprotein 1 (STIP1), which is frequently reported to be highly expressed in many cancers, in OSCCs. Methods STIP1 expression was assessed in the TCGA database and in two independent cohorts by immunohistochemistry. Knockdown strategy was applied in OSCC cell lines to determine the impact of STIP1 on viability, proliferation, migration and invasion. The zebrafish model was applied for studying tumor formation and metastasis in vivo. The association of STIP1 and miR-218-5p was explored by bioinformatics and mimics transfection. Results STIP1 was highly expressed in OSCCs and significantly associated with shortened survival and higher risk of recurrence. STIP1 down-regulation decreased proliferation, migration and invasion of tumor cells, and reduced the number of metastases in the Zebrafish model. STIP1 and miR-218-5p were inversely expressed, and the transfection of miR-218-5p mimics into OSCC cells decreased STIP1 levels as well as proliferation, migration and invasion. Conclusion Our findings show that STIP1 overexpression, which is inversely associated with miR-218-5p levels, contributes to OSCC aggressiveness by controlling proliferation, migration and invasion and is a determinant of poor prognosis.
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Affiliation(s)
- Mauricio Rocha Dourado
- Department of Oral Diagnosis, and Graduate Program in Oral Biology, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil
| | - Amr Elseragy
- Cancer and Translational Medicine Research Unit, Faculty of Medicine, and Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland
| | - Bruno Cesar da Costa
- Department of Oral Diagnosis, and Graduate Program in Oral Biology, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil
| | - Fábio Haach Téo
- Department of Oral Diagnosis, and Graduate Program in Oral Biology, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil
| | - Gustavo Narvaes Guimarães
- Department of Biosciences and Graduate Program in Oral Biology, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil
| | - Renato Assis Machado
- Department of Oral Diagnosis, and Graduate Program in Oral Biology, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil,Hospital for Rehabilitation of Craniofacial Anomalies, University of São Paulo (HRAC/USP), Bauru, São Paulo, Brazil
| | - Maija Risteli
- Cancer and Translational Medicine Research Unit, Faculty of Medicine, and Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland
| | - Wafa Wahbi
- Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, and Translational Immunology Research Program (TRIMM), University of Helsinki, Helsinki, Finland
| | - Clarissa Araujo Gurgel Rocha
- Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil,Federal University of Bahia, Salvador, Bahia, Brazil,Center for Biotechnology and Cell Therapy, D’Or Institute for Research and Education (IDOR), Salvador, Brazil
| | - Lívia Máris Ribeiro Paranaíba
- Department of Pathology and Parasitology, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil
| | | | - Sabrina Daniela da Silva
- Lady Davis Institute for Medical Research and Segal Cancer Center, Jewish General Hospital, and Department of Otolaryngology-Head and Neck Surgery, McGill University, Montreal, QC, Canada
| | | | - Marcelo Rocha Marques
- Department of Biosciences and Graduate Program in Oral Biology, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil
| | - Carlos Rossa Junior
- Department of Diagnosis and Surgery, School of Dentistry at Araraquara, São Paulo State University (UNESP), Araraquara, São Paulo, Brazil
| | - Tuula Salo
- Cancer and Translational Medicine Research Unit, Faculty of Medicine, and Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland,Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, and Translational Immunology Research Program (TRIMM), University of Helsinki, Helsinki, Finland,HUSLAB, Department of Pathology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
| | - Ricardo D. Coletta
- Department of Oral Diagnosis, and Graduate Program in Oral Biology, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil,*Correspondence: Ricardo D. Coletta,
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Abstract
The Hsp70/Hsp90 organising protein (Hop, also known as stress-inducible protein 1/STI1/STIP1) has received considerable attention for diverse cellular functions in both healthy and diseased states. There is extensive evidence that intracellular Hop is a co-chaperone of the major chaperones Hsp70 and Hsp90, playing an important role in the productive folding of Hsp90 client proteins, although recent evidence suggests that eukaryotic Hop is regulatory within chaperone complexes rather than essential. Consequently, Hop is implicated in many key signalling pathways, including aberrant pathways leading to cancer. Hop is also secreted, and it is now well established that Hop interacts with the prion protein, PrPC, to mediate multiple signalling events. The intracellular and extracellular forms of Hop most likely represent two different isoforms, although the molecular determinants of these divergent functions are yet to be identified. There is also a growing body of research that reports the involvement of Hop in cellular activities that appear independent of either chaperones or PrPC. While the various cellular functions of Hop have been described, its biological function remains elusive. However, recent knockout studies in mammals suggest that Hop has an important role in embryonic development. This review provides a critical overview of the latest molecular, cellular and biological research on Hop, critically evaluating its function in healthy systems and how this function is adapted in diseased states.
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Xie W, Sun G, Zhu J, Wang H, Han Z, Wang P. Anti-POSTN and Anti-TIMP1 Autoantibodies as Diagnostic Markers in Esophageal Squamous Cell Carcinoma. Front Genet 2022; 13:860611. [PMID: 35559040 PMCID: PMC9087588 DOI: 10.3389/fgene.2022.860611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Accepted: 03/29/2022] [Indexed: 11/13/2022] Open
Abstract
Esophageal cancer is one of the most commonly diagnosed malignant gastrointestinal tumors. The aim of the study was to explore the diagnostic values of anti-POSTN and anti-TIMP1 autoantibodies in esophageal squamous cell carcinoma (ESCC). Differentially expressed genes (DEGs) associated with esophageal cancer were screened out by the LIMMA method in the Gene Expression Profiling Interactive Analysis (GEPIA) platform. Search Tool for the Retrieval of Interacting Genes (STRING) was used to construct the protein-protein interaction (PPI) based on highly DEGs. The candidate hub genes were the intersection genes calculated based on degree and Maximal Clique Centrality (MCC) algorithms via Cytoscape. A total of 370 participants including 185 ESCC patients and 185 matched normal controls were enrolled in enzyme-linked immunosorbent assay (ELISA) to detect the expression levels of autoantibodies corresponding to POSTN and TIMP1 proteins. A total of 375 DEGs with high expression were obtained in esophageal cancer. A total of 20 hub genes were acquired using the cytoHubba plugin by degree and MCC algorithms. The expression levels of anti-POSTN and anti-TIMP1 autoantibodies were higher in the sera of ESCC patients (p < 0.05). Anti-POSTN autoantibody can diagnose ESCC patients with an AUC of 0.638 at the specificity of 90.27% and sensitivity of 27.57%, and anti-TIMP1 autoantibody can diagnose ESCC patients with an AUC of 0.585 at the specificity of 90.27% and sensitivity of 20.54% (p < 0.05). In addition, anti-POSTN and anti-TIMP1 autoantibodies can distinguish ESCC patients from normal controls in most clinical subgroups (p < 0.05). In conclusion, anti-POSTN and anti-TIMP1 autoantibodies may be considered the potential biomarkers in the clinical diagnosis of ESCC.
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Affiliation(s)
- Weihong Xie
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China
| | - Guiying Sun
- Department of Epidemiology and Statistics and State Key Laboratory of Esophageal Cancer Prevention & Treatment, College of Public Health, Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China
| | - Jicun Zhu
- Department of Epidemiology and Statistics and State Key Laboratory of Esophageal Cancer Prevention & Treatment, College of Public Health, Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China
| | - Huimin Wang
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China
- Academy of Medical Science, Zhengzhou University, Zhengzhou, China
| | - Zhuo Han
- Department of Epidemiology and Statistics and State Key Laboratory of Esophageal Cancer Prevention & Treatment, College of Public Health, Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China
| | - Peng Wang
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China
- Department of Epidemiology and Statistics and State Key Laboratory of Esophageal Cancer Prevention & Treatment, College of Public Health, Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China
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Wang M, Liu F, Pan Y, Xu R, Li F, Liu A, Yang H, Duan L, Shen L, Wu Q, Liu Y, Liu M, Liu Z, Hu Z, Chen H, Cai H, He Z, Ke Y. Tumor-associated autoantibodies in ESCC screening: Detecting prevalent early-stage malignancy or predicting future cancer risk? EBioMedicine 2021; 73:103674. [PMID: 34753106 PMCID: PMC8586741 DOI: 10.1016/j.ebiom.2021.103674] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 10/19/2021] [Accepted: 10/19/2021] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND To assess potential roles for tumor-associated autoantibodies (TAAs) in esophageal squamous cell carcinoma (ESCC) screening: detecting early-stage malignancy, and predicting future cancer risk. METHOD Thirteen candidate autoantibodies identified in previous literatures were measured using multiplex serological assays in sera from cases and matched controls nested in two population-level screening cohorts in China. To evaluate the role of TAAs in detecting prevalent esophageal malignant lesions, an identification set (150 cases vs. 560 controls) and an external validation set (34 cases vs. 121 controls) were established with pre-screening sera collected ≤ 12 months prior to screening-related diagnosis. To explore the role of TAAs in predicting future ESCC risk, an exploration set (105 cases vs. 416 controls) with pre-diagnostic sera collected > 12 months before clinical diagnosis was established. Two models, the questionnaire-based model and full model additionally incorporating TAA markers, were constructed. Area under the receiver operating characteristic curve (AUC) and net reclassification improvement (NRI) were calculated to compare the performance of the two models. FINDINGS In the identification set, NY-ESO-1 (OR=2·12, 95% CI=1·02-4·40) and STIP1 (OR=1·83, 95% CI=1·10-3·05) were positively associated with higher risk of esophageal malignancy. Elevated MMP-7 was associated with higher risk of malignancy in females (ORfemale=5·07, 95% CI=1·30-19·71). The estimates in validation set were consistent with these results, but were close to null in exploration set. Integration of selected TAAs improved the performance of questionnaire-based models in detecting prevalent esophageal malignancy (female: AUCfull model=0·745, 95% CI=0·675-0·814, AUCquestionnaire-based model=0·658, 95% CI=0·585-0·732, NRI=0·604, P<0·0001; male: AUCfull model=0·662, 95% CI=0·596-0·728, AUCquestionnaire-based model=0·619, 95% CI=0·548-0·690, NRI=0·357, P=0·0028). This improvement was also seen in validation set, but was not similarly effective in distinguishing long-term incident cases from healthy controls. INTERPRETATION Serological autoantibodies against NY-ESO-1, STIP1, and MMP-7 perform well in detecting early-stage esophageal malignancy, but are less effective in predicting future ESCC risks. FUNDING This work was supported by the National Science & Technology Fundamental Resources Investigation Program of China (2019FY101102), the National Natural Science Foundation of China (82073626), the National Key R&D Program of China (2016YFC0901404), the Beijing-Tianjin-Hebei Basic Research Cooperation Project (J200016), the Digestive Medical Coordinated Development Center of Beijing Hospitals Authority (XXZ0204), and the Natural Science Foundation of Beijing Municipality (7182033).
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Affiliation(s)
- Minmin Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Fangfang Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Yaqi Pan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Ruiping Xu
- Anyang Cancer Hospital, Anyang, Henan Province, P.R. China
| | - Fenglei Li
- Hua County People's Hospital, Anyang, Henan Province, P.R. China
| | - Anxiang Liu
- Endoscopy center, Anyang Cancer Hospital, Anyang, Henan Province, P.R. China
| | - Haijun Yang
- Department of pathology, Anyang Cancer Hospital, Anyang, Henan Province, P.R. China
| | - Liping Duan
- Department of Gastroenterology, Peking University Third Hospital, Beijing, P.R. China
| | - Lin Shen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Qi Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Endoscopy Center, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Ying Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Mengfei Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Zhen Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Zhe Hu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Huanyu Chen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Hong Cai
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Zhonghu He
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China.
| | - Yang Ke
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China.
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Wang H, Yang X, Sun G, Yang Q, Cui C, Wang X, Ye H, Dai L, Shi J, Zhang J, Wang P. Identification and Evaluation of Autoantibody to a Novel Tumor-Associated Antigen GNA11 as a Biomarker in Esophageal Squamous Cell Carcinoma. Front Oncol 2021; 11:661043. [PMID: 34568004 PMCID: PMC8462091 DOI: 10.3389/fonc.2021.661043] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Accepted: 08/18/2021] [Indexed: 12/15/2022] Open
Abstract
The study aims to explore the diagnostic value of anti-GNA11 autoantibody in esophageal squamous cell carcinoma (ESCC) from multiple levels. Autoantibody against GNA11 with the highest diagnostic performance was screened out from the customized protein microarray. A total of 486 subjects including ESCC patients and matched normal controls were recruited in the verification and validation phases by using enzyme-linked immunosorbent assay (ELISA). Western blotting analysis was used to verify the ELISA results. Immunohistochemistry (IHC) was used to evaluate GNA11 expression in ESCC tissues and para-tumor tissues. In addition, a bioinformatics approach was adopted to investigate the mRNA expression of GNA11 in ESCC. Results indicated that the level of anti-GNA11 autoantibody in ESCC patients was significantly higher than that in the normal controls, and it can be used to distinguish ESCC patients from normal individuals in clinical subgroups (p < 0.05), as revealed by both ELISA and Western blotting. The receiver operating characteristic (ROC) curve analysis showed that anti-GNA11 autoantibody could distinguish ESCC patients from normal controls with an area under the ROC curve (AUC) of 0.653, sensitivity of 10.96%, and specificity of 98.63% in the verification cohort and with an AUC of 0.751, sensitivity of 38.24%, and specificity of 88.82% in the validation cohort. IHC manifested that the expression of GNA11 can differentiate ESCC tissues with para-tumor tissues (p < 0.05), but it cannot be used to differentiate different pathological grades and clinical stages (p > 0.05). The mRNA expression of GNA11 in ESCC patients and normal controls was different with a bioinformatics mining with The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data in Gene Expression Profiling Interactive Analysis (GEPIA). In summary, anti-GNA11 autoantibody has the potential to be a new serological marker in the diagnosis of ESCC.
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Affiliation(s)
- Huimin Wang
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China.,School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.,Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China.,College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Xiaoang Yang
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China
| | - Guiying Sun
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China.,College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Qian Yang
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China.,College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Chi Cui
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China.,Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China
| | - Xiao Wang
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China.,Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China
| | - Hua Ye
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China.,College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Liping Dai
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China.,Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China
| | - Jianxiang Shi
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China.,Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China
| | - Jianying Zhang
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China.,Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China
| | - Peng Wang
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China.,Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China.,College of Public Health, Zhengzhou University, Zhengzhou, China
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Yang SH, Liu CT, Hong CQ, Huang ZY, Wang HZ, Wei LF, Lin YW, Guo HP, Peng YH, Xu YW. Autoantibodies against p53, MMP-7, and Hsp70 as Potential Biomarkers for Detection of Nonmelanoma Skin Cancers. DISEASE MARKERS 2021; 2021:5592693. [PMID: 34336006 PMCID: PMC8289574 DOI: 10.1155/2021/5592693] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 05/31/2021] [Indexed: 02/05/2023]
Abstract
Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are two predominant histological types of nonmelanoma skin cancer (NMSC), lacking effective early diagnostic markers. In this study, we assessed the diagnostic value of autoantibodies against p53, MMP-7, and Hsp70 in skin SCC and BCC. ELISA was performed to detect levels of autoantibodies in sera from 101 NMSC patients and 102 normal controls, who were recruited from the Cancer Hospital of Shantou University Medical College. A receiver operator characteristic curve was used to evaluate the diagnostic value. The serum levels of autoantibodies against p53, MMP-7, and Hsp70 were higher in NMSCs than those in the normal controls (all P < 0.01). The AUC of the three-autoantibody panel was 0.841 (95% CI: 0.788-0.894) with the sensitivity and specificity of 60.40% and 91.20% when differentiating NMSCs from normal controls. Furthermore, measurement of this panel could differentiate early-stage skin cancer patients from normal controls (AUC: 0.851; 95% CI: 0.793-0.908). Data from Oncomine showed that the level of p53 mRNA was elevated in BCC (P < 0.05), and the Hsp70 mRNA was upregulated in SCC (P < 0.001). This serum three-autoantibody panel might function in assisting the early diagnosis of NMSC.
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Affiliation(s)
- Shi-Han Yang
- Department of Dermatology and Venereology, Affiliated Shantou Hospital of Sun Yat-sen University, 114 Waima Road, Shantou 515041, China
| | - Can-Tong Liu
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou 515041, China
- Precision Medicine Research Center, Shantou University Medical College, 22 Xinling Road, Shantou 515041, China
| | - Chao-Qun Hong
- Department of Oncological Laboratory Research, The Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou 515041, China
| | - Ze-Yuan Huang
- Department of Dermatology and Venereology, Affiliated Shantou Hospital of Sun Yat-sen University, 114 Waima Road, Shantou 515041, China
| | - Huan-Zhu Wang
- Department of Dermatology and Venereology, Affiliated Shantou Hospital of Sun Yat-sen University, 114 Waima Road, Shantou 515041, China
| | - Lai-Feng Wei
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou 515041, China
- Precision Medicine Research Center, Shantou University Medical College, 22 Xinling Road, Shantou 515041, China
| | - Yi-Wei Lin
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou 515041, China
- Precision Medicine Research Center, Shantou University Medical College, 22 Xinling Road, Shantou 515041, China
| | - Hai-Peng Guo
- Department of Head and Neck Surgery, The Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou 515041, China
| | - Yu-Hui Peng
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou 515041, China
- Precision Medicine Research Center, Shantou University Medical College, 22 Xinling Road, Shantou 515041, China
- Guangdong Esophageal Cancer Research Institute, Shantou University Medical College, 22 Xinling Road, Shantou 515041, China
| | - Yi-Wei Xu
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou 515041, China
- Precision Medicine Research Center, Shantou University Medical College, 22 Xinling Road, Shantou 515041, China
- Guangdong Esophageal Cancer Research Institute, Shantou University Medical College, 22 Xinling Road, Shantou 515041, China
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8
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Yang X, Suo C, Zhang T, Yin X, Man J, Yuan Z, Yu J, Jin L, Chen X, Lu M, Ye W. Targeted proteomics-derived biomarker profile develops a multi-protein classifier in liquid biopsies for early detection of esophageal squamous cell carcinoma from a population-based case-control study. Biomark Res 2021; 9:12. [PMID: 33597040 PMCID: PMC7890600 DOI: 10.1186/s40364-021-00266-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 02/04/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Early diagnosis of esophageal squamous cell carcinoma (ESCC) remains a challenge due to the lack of specific blood biomarkers. We aimed to develop a serum multi-protein signature for the early detection of ESCC. METHODS We selected 70 healthy controls, 30 precancerous patients, 60 stage I patients, 70 stage II patients and 70 stage III/IV ESCC patients from a completed ESCC case-control study in a high-risk area of China. Olink Multiplex Oncology II targeted proteomics panel was used to simultaneously detect the levels of 92 cancer-related proteins in serum using proximity extension assay. RESULTS We found that 10 upregulated and 13 downregulated protein biomarkers in serum could distinguish the early-stage ESCC from healthy controls, which were validated by the significant dose-response relationships with ESCC pathological progression. Applying least absolute shrinkage and selection operator (LASSO) regression and backward elimination algorithm, ANXA1 (annexin A1), hK8 (kallikrein-8), hK14 (kallikrein-14), VIM (vimentin), and RSPO3 (R-spondin-3) were kept in the final model to discriminate early ESCC cases from healthy controls with an area under curve (AUC) of 0.936 (95% confidence interval: 0.899 ~ 0.973). The average accuracy rates of the five-protein classifier were 0.861 and 0.825 in training and test data by five-fold cross-validation. CONCLUSIONS Our study suggested that a combination of ANXA1, hK8, hK14, VIM and RSPO3 serum proteins could be considered as a potential tool for screening and early diagnosis of ESCC, especially with the establishment of a three-level hierarchical screening strategy for ESCC control.
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Affiliation(s)
- Xiaorong Yang
- Clinical Epidemiology Unit, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, China.,Clinical Research Center of Shandong University, Qilu Hospital of Shandong University, Jinan, China
| | - Chen Suo
- Department of Epidemiology and Health Statistics, School of Public Health, Fudan University, Shanghai, China
| | - Tongchao Zhang
- Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan, China
| | - Xiaolin Yin
- Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan, China
| | - Jinyu Man
- Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan, China
| | - Ziyu Yuan
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Jingru Yu
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Li Jin
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China.,State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Songhu Road 2005, Shanghai, 200438, China
| | - Xingdong Chen
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China. .,State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Songhu Road 2005, Shanghai, 200438, China.
| | - Ming Lu
- Clinical Epidemiology Unit, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, China. .,Clinical Research Center of Shandong University, Qilu Hospital of Shandong University, Jinan, China. .,Fudan University Taizhou Institute of Health Sciences, Taizhou, China.
| | - Weimin Ye
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China.,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.,Department of Epidemiology and Health Statistics & Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
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9
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Nishimura T, Nakamura H, Tan KT, Zhuo DW, Fujii K, Koizumi H, Naruki S, Takagi M, Furuya N, Kato Y, Chen SJ, Kato H, Saji H. A proteogenomic profile of early lung adenocarcinomas by protein co-expression network and genomic alteration analysis. Sci Rep 2020; 10:13604. [PMID: 32788598 PMCID: PMC7423934 DOI: 10.1038/s41598-020-70578-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Accepted: 07/24/2020] [Indexed: 12/15/2022] Open
Abstract
The tumourigenesis of early lung adenocarcinomas, including adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and lepidic predominant invasive adenocarcinoma (LPA), remains unclear. This study aimed to capture disease-related molecular networks characterising each subtype and tumorigenesis by assessing 14 lung adenocarcinomas (AIS, five; MIA, five; LPA, four). Protein-protein interaction networks significant to the three subtypes were elucidated by weighted gene co-expression network analysis and pairwise G-statistics based analysis. Pathway enrichment analysis for AIS involved extracellular matrix proteoglycans and neutrophil degranulation pathway relating to tumour growth and angiogenesis. Whereas no direct networks were found for MIA, proteins significant to MIA were involved in oncogenic transformation, epithelial-mesenchymal transition, and detoxification in the lung. LPA was associated with pathways of HSF1-mediated heat shock response regulation, DNA damage repair, cell cycle regulation, and mitosis. Genomic alteration analysis suggested that LPA had both somatic mutations with loss of function and copy number gains more frequent than MIA. Oncogenic drivers were detected in both MIA and LPA, and also LPA had a higher degree of copy number loss than MIA. Our findings may help identifying potential therapeutic targets and developing therapeutic strategies to improve patient outcomes.
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Affiliation(s)
- Toshihide Nishimura
- Department of Translational Medicine Informatics, St. Marianna University School of Medicine, Kawasaki, Kanagawa, 216-8511, Japan.
- Department of Chest Surgery, St. Marianna University School of Medicine, Kawasaki, Kanagawa, 216-8511, Japan.
| | - Haruhiko Nakamura
- Department of Translational Medicine Informatics, St. Marianna University School of Medicine, Kawasaki, Kanagawa, 216-8511, Japan
- Department of Chest Surgery, St. Marianna University School of Medicine, Kawasaki, Kanagawa, 216-8511, Japan
| | | | | | - Kiyonaga Fujii
- Department of Translational Medicine Informatics, St. Marianna University School of Medicine, Kawasaki, Kanagawa, 216-8511, Japan
- Department of Chest Surgery, St. Marianna University School of Medicine, Kawasaki, Kanagawa, 216-8511, Japan
| | - Hirotaka Koizumi
- Department of Pathology, St. Marianna University Hospital, Kawasaki, Kanagawa, 216-8511, Japan
| | - Saeko Naruki
- Department of Pathology, St. Marianna University Hospital, Kawasaki, Kanagawa, 216-8511, Japan
| | - Masayuki Takagi
- Department of Pathology, St. Marianna University Hospital, Kawasaki, Kanagawa, 216-8511, Japan
| | - Naoki Furuya
- Division of Respiratory Medicine, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, 216-8511, Japan
| | - Yasufumi Kato
- Department of Thoracic Surgery, Kanto Central Hospital, Tokyo, 158-8531, Japan
| | | | - Harubumi Kato
- Tokyo Medical University, Tokyo, 160-0023, Japan
- International University of Health and Welfare, Tokyo, 107-8402, Japan
| | - Hisashi Saji
- Department of Chest Surgery, St. Marianna University School of Medicine, Kawasaki, Kanagawa, 216-8511, Japan
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10
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Tumor-associated antigens and their antibodies in the screening, diagnosis, and monitoring of esophageal cancers. Eur J Gastroenterol Hepatol 2020; 32:779-788. [PMID: 32243347 DOI: 10.1097/meg.0000000000001718] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Despite the advances in the treatment and management, esophageal cancers continue to carry a dismal prognosis with an overall 5-year survival rate ranging from 15 to 25%. Delayed onset of symptoms and lack of effective screening methods and guidelines for diagnosis of the early disease contribute to the high mortality rate of esophageal cancers. Detection of esophageal cancer at their early stage is really a challenge for physicians including primary care physicians, gastroenterologists and oncologists. Although imaging, endoscopy and biopsy have been proved to be useful diagnostic tools for esophageal cancers, their diagnostic accuracy is unsatisfactory. In addition, expensive costs, invasiveness and special training operator have limited the clinical application of these tools. Recently, tumor-associated antigens (TAAs) and their antibodies have been reported to be potential markers in esophageal cancer screening, diagnosis, monitoring and prognostication. Because TAAs and their antibodies have the advantages of inexpensive cost, noninvasiveness and easy access, they have attracted much attention as an affordable option for early esophageal cancer diagnosis. In this review, we summarized the advances in TAAs and their antibodies in esophageal cancer screening, diagnosis, monitoring and prognostication.
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11
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da Fonseca ACC, Matias D, Geraldo LHM, Leser FS, Pagnoncelli I, Garcia C, do Amaral RF, da Rosa BG, Grimaldi I, de Camargo Magalhães ES, Cóppola-Segovia V, de Azevedo EM, Zanata SM, Lima FRS. The multiple functions of the co-chaperone stress inducible protein 1. Cytokine Growth Factor Rev 2020; 57:73-84. [PMID: 32561134 DOI: 10.1016/j.cytogfr.2020.06.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 05/22/2020] [Accepted: 06/02/2020] [Indexed: 12/18/2022]
Abstract
Stress inducible protein 1 (STI1) is a co-chaperone acting with Hsp70 and Hsp90 for the correct client proteins' folding and therefore for the maintenance of cellular homeostasis. Besides being expressed in the cytosol, STI1 can also be found both in the cell membrane and the extracellular medium playing several relevant roles in the central nervous system (CNS) and tumor microenvironment. During CNS development, in association with cellular prion protein (PrPc), STI1 regulates crucial events such as neuroprotection, neuritogenesis, astrocyte differentiation and survival. In cancer, STI1 is involved with tumor growth and invasion, is undoubtedly a pro-tumor factor, being considered as a biomarker and possibly therapeutic target for several malignancies. In this review, we discuss current knowledge and new findings on STI1 function as well as its role in tissue homeostasis, CNS and tumor progression.
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Affiliation(s)
| | - Diana Matias
- Molecular Bionics Laboratory, Department of Chemistry, University College London, London, WC1H 0AJ, United Kingdom
| | - Luiz Henrique Medeiros Geraldo
- Glial Cell Biology Laboratory, Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, 21949-590, Brazil; Université de Paris, PARCC, INSERM, Paris, 75015, France
| | - Felipe Saceanu Leser
- Glial Cell Biology Laboratory, Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, 21949-590, Brazil
| | - Iohana Pagnoncelli
- Glial Cell Biology Laboratory, Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, 21949-590, Brazil
| | - Celina Garcia
- Glial Cell Biology Laboratory, Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, 21949-590, Brazil
| | - Rackele Ferreira do Amaral
- Glial Cell Biology Laboratory, Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, 21949-590, Brazil
| | - Barbara Gomes da Rosa
- Glial Cell Biology Laboratory, Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, 21949-590, Brazil
| | - Izabella Grimaldi
- Glial Cell Biology Laboratory, Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, 21949-590, Brazil
| | - Eduardo Sabino de Camargo Magalhães
- Glial Cell Biology Laboratory, Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, 21949-590, Brazil; European Research Institute for the Biology of Aging, University of Groningen, Groningen, 9713 AV, Netherlands
| | - Valentín Cóppola-Segovia
- Departments of Basic Pathology and Cell Biology, Federal University of Paraná, Paraná, RJ, 81531-970, Brazil
| | - Evellyn Mayla de Azevedo
- Departments of Basic Pathology and Cell Biology, Federal University of Paraná, Paraná, RJ, 81531-970, Brazil
| | - Silvio Marques Zanata
- Departments of Basic Pathology and Cell Biology, Federal University of Paraná, Paraná, RJ, 81531-970, Brazil
| | - Flavia Regina Souza Lima
- Glial Cell Biology Laboratory, Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, 21949-590, Brazil.
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12
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Khan T, Relitti N, Brindisi M, Magnano S, Zisterer D, Gemma S, Butini S, Campiani G. Autophagy modulators for the treatment of oral and esophageal squamous cell carcinomas. Med Res Rev 2019; 40:1002-1060. [PMID: 31742748 DOI: 10.1002/med.21646] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Revised: 10/16/2019] [Accepted: 11/08/2019] [Indexed: 02/06/2023]
Abstract
Oral squamous cell carcinomas (OSCC) and esophageal squamous cell carcinomas (ESCC) exhibit a survival rate of less than 60% and 40%, respectively. Late-stage diagnosis and lack of effective treatment strategies make both OSCC and ESCC a significant health burden. Autophagy, a lysosome-dependent catabolic process, involves the degradation of intracellular components to maintain cell homeostasis. Targeting autophagy has been highlighted as a feasible therapeutic strategy with clinical utility in cancer treatment, although its associated regulatory mechanisms remain elusive. The detection of relevant biomarkers in biological fluids has been anticipated to facilitate early diagnosis and/or prognosis for these tumors. In this context, recent studies have indicated the presence of specific proteins and small RNAs, detectable in circulating plasma and serum, as biomarkers. Interestingly, the interplay between biomarkers (eg, exosomal microRNAs) and autophagic processes could be exploited in the quest for targeted and more effective therapies for OSCC and ESCC. In this review, we give an overview of the available biomarkers and innovative targeted therapeutic strategies, including the application of autophagy modulators in OSCC and ESCC. Additionally, we provide a viewpoint on the state of the art and on future therapeutic perspectives combining the early detection of relevant biomarkers with drug discovery for the treatment of OSCC and ESCC.
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Affiliation(s)
- Tuhina Khan
- Department of Biotechnology, Chemistry, and Pharmacy, Department of Excellence 2018-2022, University of Siena, Siena, Italy
| | - Nicola Relitti
- Department of Biotechnology, Chemistry, and Pharmacy, Department of Excellence 2018-2022, University of Siena, Siena, Italy
| | - Margherita Brindisi
- Department of Pharmacy, Department of Excellence 2018-2022, University of Napoli Federico IL, Napoli, Italy
| | - Stefania Magnano
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, 152-160, Pearse Street, Dublin, Dublin 2, Ireland
| | - Daniela Zisterer
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, 152-160, Pearse Street, Dublin, Dublin 2, Ireland
| | - Sandra Gemma
- Department of Biotechnology, Chemistry, and Pharmacy, Department of Excellence 2018-2022, University of Siena, Siena, Italy
| | - Stefania Butini
- Department of Biotechnology, Chemistry, and Pharmacy, Department of Excellence 2018-2022, University of Siena, Siena, Italy
| | - Giuseppe Campiani
- Department of Biotechnology, Chemistry, and Pharmacy, Department of Excellence 2018-2022, University of Siena, Siena, Italy
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13
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Xu YW, Peng YH, Xu LY, Xie JJ, Li EM. Autoantibodies: Potential clinical applications in early detection of esophageal squamous cell carcinoma and esophagogastric junction adenocarcinoma. World J Gastroenterol 2019; 25:5049-5068. [PMID: 31558856 PMCID: PMC6747294 DOI: 10.3748/wjg.v25.i34.5049] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Revised: 07/28/2019] [Accepted: 08/19/2019] [Indexed: 02/06/2023] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) and esophagogastric junction adenocarcinoma (EGJA) are the two main types of gastrointestinal cancers that pose a huge threat to human health. ESCC remains one of the most common malignant diseases around the world. In contrast to the decreasing prevalence of ESCC, the incidence of EGJA is rising rapidly. Early detection represents one of the most promising ways to improve the prognosis and reduce the mortality of these cancers. Current approaches for early diagnosis mainly depend on invasive and costly endoscopy. Non-invasive biomarkers are in great need to facilitate earlier detection for better clinical management of patients. Tumor-associated autoantibodies can be detected at an early stage before manifestations of clinical signs of tumorigenesis, making them promising biomarkers for early detection and monitoring of ESCC and EGJA. In this review, we summarize recent insights into the iden-tification and validation of tumor-associated autoantibodies for the early detection of ESCC and EGJA and discuss the challenges remaining for clinical validation.
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Affiliation(s)
- Yi-Wei Xu
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Yu-Hui Peng
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Li-Yan Xu
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong Province, China
- Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Jian-Jun Xie
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong Province, China
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - En-Min Li
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong Province, China
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong Province, China
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14
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Down-regulation of STIP1 regulate apoptosis and invasion of glioma cells via TRAP1/AKT signaling pathway. Cancer Genet 2019; 237:1-9. [PMID: 31447061 DOI: 10.1016/j.cancergen.2019.05.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 04/15/2019] [Accepted: 05/29/2019] [Indexed: 12/16/2022]
Abstract
BACKGROUND In recent years, many studies have confirmed that STIP1 (phosphorylation-induced protein 1) is involved in the development and progression of various tumors. However, its potential role in glioma progression and the underlying mechanisms of glioma development remain unclear. METHODS We analyzed the expression of STIP1 in 35 human glioma tissue specimens of different grades, using 6 normal brain tissues for comparison. We transfected U87 and U251 cell lines with small interfering RNA (siRNA) to downregulate STIP1, and set up a negative control group and a blank group for comparison. The MTT assay was used to detect cell proliferation, and cell cycle progression and apoptosis were analyzed through flow cytometry. Transwell experiments were employed to detect the invasion and migration of STIP1-depleted and control U87 and U251 cells and western blotting was used to detect the expression of TRAP1/Akt pathway proteins. In addition, immunohistochemical analysis was used to reveal differences in expression and localization between transplanted tumor specimens of each group. RESULTS We observed a high expression of STIP1 in glioblastoma, MTT assay revealed a decreased cell proliferation rate in the STIP1-downregulated cells. Cell cycle analysis revealed an increased proportion of cells in G1 phase, as well as an increase in apoptosis, upon STIP1 downregulation. Western blotting showed that TRAP1, pAkt, and MMP2 expression was decreased upon STIP1 downregulation. In addition, TRAP1, ki-67, and MMP2 displayed a decreased expression in vivo. CONCLUSIONS STIP1 is highly expressed in glioblastoma compared to normal brain tissues. Downregulation of STIP1 in glioma cells reduces cell proliferation rate and invasion and increases cell apoptosis.
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