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Chaudhary RK, Patil P, Mateti UV, Alagundagi DB, Shetty V. Theranostic Potential of EFNB2 for Cetuximab Resistance in Head and Neck Cancer. Indian J Otolaryngol Head Neck Surg 2023; 75:1923-1936. [PMID: 37636764 PMCID: PMC10447808 DOI: 10.1007/s12070-023-03739-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 03/26/2023] [Indexed: 08/29/2023] Open
Abstract
Only 13% of head and neck cancer (HNC) patients respond to cetuximab therapy despite its target (EGFR) is expressed in about 80-90% of HNC patients. However, this problem remained unresolved till date despite of numerous efforts. Thus, the current study aimed to establish hub genes involved in cetuximab resistance via series of bioinformatics approach. The GSE21483 dataset was analysed for differentially expressed genes (DEGs) using GEO2R and enrichment analysis was carried out using DAVID. STRING 11.5 and Cytoscape 3.7.2 were used for protein-protein interactions and hub genes respectively. The significant hub genes (p < 0.05) were validated using ULCAN and Human protein atlas. Validated genes were further queried for tumor infiltration using TIMER2.0. Out of total 307 DEGs, 38 hub genes were identified of which IL1A, EFNB2, SPRR1A, ROBO1 and SOCS3 were the significant hub genes associated with both mRNA expression and overall survival. IL1A, ROBO1, and SOCS3 were found to be downregulated whereas EFNB2 and SPRR1A were found to be upregulated in our study. However, using UALCAN, we found that high expression of IL1A, EFNB2, SOCS3 negatively affects overall survival whereas high expression of SPRR1A and ROBO1 positively affects overall survival. Protein level for EFNB2 and SPRR1A expression was significant in tumor HNC tissue as compared to normal HNC tissue. EFNB2 was found to be a key regulator of CTX resistance among HNC patients. Targeting EFNB2 and associated PPI circuits might improve the response rate to CTX. Thus, EFNB2 has potential to be theranostic marker for CTX resistance. Supplementary Information The online version contains supplementary material available at 10.1007/s12070-023-03739-9.
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Affiliation(s)
- Raushan Kumar Chaudhary
- Department of Pharmacy Practice, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University), Deralakatte, Mangaluru, Karnataka 575018 India
| | - Prakash Patil
- Central Research Laboratory, K.S. Hegde Medical Academy (KSHEMA), Nitte (Deemed to be University), Deralakatte, Mangaluru, Karnataka 575018 India
| | - Uday Venkat Mateti
- Department of Pharmacy Practice, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University), Deralakatte, Mangaluru, Karnataka 575018 India
| | - Dhananjay B. Alagundagi
- Central Research Laboratory, K.S. Hegde Medical Academy (KSHEMA), Nitte (Deemed to be University), Deralakatte, Mangaluru, Karnataka 575018 India
| | - Vijith Shetty
- Department of Medical Oncology, K.S. Hegde Medical Academy (KSHEMA), Justice K.S. Hegde Charitable Hospital, Nitte (Deemed to be University), Deralakatte, Mangaluru, Karnataka 575018 India
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Survival-related indicators ALOX12B and SPRR1A are associated with DNA damage repair and tumor microenvironment status in HPV 16-negative head and neck squamous cell carcinoma patients. BMC Cancer 2022; 22:714. [PMID: 35768785 PMCID: PMC9241267 DOI: 10.1186/s12885-022-09722-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 05/30/2022] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVES To investigate prognostic-related gene signature based on DNA damage repair and tumor microenvironment statue in human papillomavirus 16 negative (HPV16-) head and neck squamous cell carcinoma (HNSCC). METHODS For the RNA-sequence matrix in HPV16- HNSCC in the Cancer Genome Atlas (TCGA) cohort, the DNA damage response (DDR) and tumor microenvironment (TM) status of each patient sample was estimated by using the ssGSEA algorithm. Through bioinformatics analysis in DDR_high/TM_high (n = 311) and DDR_high/TM_low (n = 53) groups, a survival-related gene signature was selected in the TCGA cohort. Two independent external validation cohorts (GSE65858 (n = 210) and GSE41613 (n = 97)) with HPV16- HNSCC patients validated the gene signature. Correlations among the clinical-related hub differentially expressed genes (DEGs) and infiltrated immunocytes were explored with the TIMER2.0 server. Drug screening based on hub DEGs was performed using the CellMiner and GSCALite databases. The loss-of-function studies were used to evaluate the effect of screened survival-related gene on the motility of HPV- HNSCC cells in vitro. RESULTS A high DDR level (P = 0.025) and low TM score (P = 0.012) were independent risk factors for HPV16- HNSCC. Downregulated expression of ALOX12B or SPRR1A was associated with poor survival rate and advanced cancer stages. The pathway enrichment analysis showed the DDR_high/TM_low samples were enriched in glycosphingolipid biosynthesis-lacto and neolacto series, glutathione metabolism, platinum drug resistance, and ferroptosis pathways, while the DDR_high/TM_low samples were enriched in Th17 cell differentiation, Neutrophil extracellular trap formation, PD - L1 expression and PD - 1 checkpoint pathway in cancer. Notably, the expression of ALOX12B and SPRR1A were negatively correlated with cancer-associated fibroblasts (CAFs) infiltration and CAFs downstream effectors. Sensitivity to specific chemotherapy regimens can be derived from gene expressions. In addition, ALOX12B and SPRR1A expression was associated with the mRNA expression of insulin like growth factor 1 receptor (IGF1R), AKT serine/threonine kinase 1 (AKT1), mammalian target of rapamycin (MTOR), and eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1) in HPV negative HNSCC. Down-regulation of ALOX12B promoted HPV- HNSCC cells migration and invasion in vitro. CONCLUSIONS ALOX12B and SPRR1A served as a gene signature for overall survival in HPV16- HNSCC patients, and correlated with the amount of infiltrated CAFs. The specific drug pattern was determined by the gene signature.
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A Novel 2-Metagene Signature to Identify High-Risk HNSCC Patients amongst Those Who Are Clinically at Intermediate Risk and Are Treated with PORT. Cancers (Basel) 2022; 14:cancers14123031. [PMID: 35740697 PMCID: PMC9221048 DOI: 10.3390/cancers14123031] [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: 05/03/2022] [Revised: 06/13/2022] [Accepted: 06/15/2022] [Indexed: 12/10/2022] Open
Abstract
(1) Background: Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who are biologically at high risk for the development of loco−regional recurrences after postoperative radiotherapy (PORT) but at intermediate risk according to clinical risk factors may benefit from additional concurrent chemotherapy. In this matched-pair study, we aimed to identify a corresponding predictive gene signature. (2) Methods: Gene expression analysis was performed on a multicenter retrospective cohort of 221 patients that were treated with postoperative radiochemotherapy (PORT-C) and 283 patients who were treated with PORT alone. Propensity score analysis was used to identify matched patient pairs from both cohorts. From differential gene expression analysis and Cox regression, a predictive gene signature was identified. (3) Results: 108 matched patient pairs were selected. We identified a 2-metagene signature that stratified patients into risk groups in both cohorts. The comparison of the high-risk patients between the two types of treatment showed higher loco−regional control (LRC) after treatment with PORT-C (p < 0.001), which was confirmed by a significant interaction term in Cox regression (p = 0.027), i.e., the 2-metagene signature was indicative for the type of treatment. (4) Conclusion: We have identified a novel gene signature that may be helpful to identify patients with high-risk HNSCC amongst those at intermediate clinical risk treated with PORT, who may benefit from additional concurrent chemotherapy.
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Wang S, Zhang W. Small Proline Rich Protein 1A promotes lung adenocarcinoma progression and indicates unfavorable clinical outcomes. Biochem Cell Biol 2022; 100:199-212. [PMID: 35263193 DOI: 10.1139/bcb-2021-0348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Small Proline Rich Protein 1A (SPRR1A) plays a critical role in regulating squamous cell differentiation. It has been reported that SPRR1A overexpression was closely related to the progression of some tumors such as gastric cancer and colon cancer. However, the function of SPRR1A in lung adenocarcinoma (LUAD) has not been elucidated. Here we firstly examined the expression pattern of SPRR1A in LUAD tissues, which indicated that SPRR1A expression level was significantly elevated in LUAD tissues compared to normal lung tissues. High expression of SPRR1A was closely related to the larger tumor size. LUAD patients with higher SPRR1A expression had poorer overall survival and SPRR1A was identified as an independent unfavorable prognosis factor. In addition, the effects of SPRR1A on lung cancer cells were tested through cellular experiments and the result demonstrated that knockdown of SPRR1A can suppress proliferation and invasion capacities of tumor cells, while overexpressing SPRR1A exerted opposite effects. Finally, our findings were substantiated by the data obtained from in vivo xenografts using mice model. In conclusion, LUAD patients with higher SPRR1A expression were more predisposed to poorer clinical outcomes and unfavorable prognosis, indicating the potential role of SPRR1A as a novel clinical biomarker and therapeutic target.
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Affiliation(s)
- Shenqi Wang
- Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Department of Respiratory Medicine, Shanghai, China;
| | - Wenmei Zhang
- Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Department of Respiratory Medicine, Shanghai, China, 200336;
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Sun J, Fang G, Zuo Z, Yu X, Xue L, Li C, Li S. Identification of Immune Subtypes for Predicting the Prognosis of Patients in Head and Neck Squamous Cell Carcinoma. Technol Cancer Res Treat 2021; 20:15330338211045823. [PMID: 34657509 PMCID: PMC8521413 DOI: 10.1177/15330338211045823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
Head and neck squamous cell carcinoma (HNSCC) is a common malignancy with poor prognosis and immune response, which plays an important role in tumor progression. Recently, immunotherapies have revolutionized the therapeutic means of malignancies including HNSCC. However, the relationship between immunophenotypes of HNSCC and its clinical response to immune-checkpoint inhibitors remains unclear. We aim to identify molecular subtyping related to distinct immunophenotypes in HNSCC. Consensus clustering algorithm was conducted for subtyping. Immunophenotypes between subtypes were compared according to infiltrating immunocytes, immune reactions, major histocompatibility complex (MHC) family, immunoinhibitory, immunostimulatory and immune scores. The relationship between immunophenotype and genotype was investigated from gene mutation and tumor mutation burden. The potential response of Immune-checkpoint blockade (ICB) therapy was estimated with TIDE and ImmuCellAI algorithms, and immune-checkpoint genes. The immune characteristics were also investigated. Biological functions were annotated by the gene-set enrichment analysis (GSEA) algorithm. Two distinct immune subtypes of HNSCC with different survival outcomes, biological characteristics, immunophenotype, and ICB response were identified. The subtype-1 was featured with better prognosis, more infiltrated immunocytes, stronger immune reaction, higher immune-related gene expression, higher immune-checkpoint gene expression (PD-1, PD-L1, and CTLA-4), and better ICB response. A higher immune response in subtype-1 was also revealed by GSEA. Subtype-1 possessed a higher immune response and more sensitivity to ICB therapy leading to a better prognosis. These findings may shed promising light on the immunotherapy strategy in HNSCC
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Affiliation(s)
- Jing Sun
- Department of Periodontology, Jinan Stomatological Hospital, Jinan, China
- Jing Sun, No.101 Jingliu Road, Jinan, Shandong 250001, People's Republic of China.
| | - Guiqing Fang
- Department of Periodontology, Jinan Stomatological Hospital, Jinan, China
- Jing Sun, No.101 Jingliu Road, Jinan, Shandong 250001, People's Republic of China.
| | - Zhibin Zuo
- Department of Periodontology, Jinan Stomatological Hospital, Jinan, China
| | - Xijiao Yu
- Department of Periodontology, Jinan Stomatological Hospital, Jinan, China
| | - Lande Xue
- Department of Periodontology, Jinan Stomatological Hospital, Jinan, China
| | - Chong Li
- Department of Periodontology, Jinan Stomatological Hospital, Jinan, China
- Chong Li, No.44 to 1 Wenhua Road West, 250012, Jinan, Shandong, China.
| | - Shu Li
- Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China
- Shu Li, Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, China.
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Yao L, Yan J, Cheng F, Gan L, Huang Y, Zheng L, Fang N. Small Proline-Rich Protein 2B Facilitates Gastric Adenocarcinoma Proliferation via MDM2-p53/p21 Signaling Pathway. Onco Targets Ther 2021; 14:1453-1463. [PMID: 33664578 PMCID: PMC7924129 DOI: 10.2147/ott.s281032] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 01/13/2021] [Indexed: 12/29/2022] Open
Abstract
Background The small proline-rich protein 2B (SPRR2B) was firstly reported as a member of the cross-linked envelope protein in keratinocytes. The effect of SPRR2B in gastric adenocarcinoma (GC) remains unclear. This study initially explored the clinical significance of SPRR2B in GC patients as well as its role in tumor progression. Methods Immunohistochemistry was performed to characterize the expression of SPRR2B in GC tissues and adjacent tissues. The relationship between SPRR2B expression and clinicopathological features of GC patients was analyzed by Chi-square test. Kaplan-Meier method and Cox regression analyses were utilized to identify the prognostic factors of GC. Overexpression and knockdown assays were conducted to investigate possible signaling pathways downstream of SPRR2B. Flow cytometry assays were performed to evaluate cell cycle and apoptosis. Xenograft experiments were performed to validate tumor-related role of SPRR2B in vivo. Results Both mRNA and protein levels of SPRR2B in cancerous tissue were significantly higher than those in non-cancerous tissues. Meanwhile, SPRR2B expression was significantly associated with tumor size and tumor stage. Survival analysis revealed SPRR2B as one of the independent prognosis factors for overall survival of GC patients. Cellular and xenografts data implicated that silencing SPRR2B blocked the cell cycle of GC cells perhaps through MDM2-p53/p21-CDK1 pathway, while overexpressing SPRR2B exhibited opposite effects. Conclusion Our data suggest that SPRR2B may serve as a novel prognostic marker in GC, which functions at least partially by MDM2-p53/p21-CDK1 signaling pathway.
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Affiliation(s)
- Ling Yao
- Department of Gastroenterology, Third Affiliated Hospital of Nanchang University, Nanchang, 330008, Jiangxi Province, People's Republic of China
| | - Jinhua Yan
- Department of Hematology, Third Affiliated Hospital of Nanchang University, Nanchang, 330008, Jiangxi Province, People's Republic of China
| | - Fei Cheng
- Department of Gastroenterology, Third Affiliated Hospital of Nanchang University, Nanchang, 330008, Jiangxi Province, People's Republic of China
| | - Lihong Gan
- Department of Gastroenterology, Third Affiliated Hospital of Nanchang University, Nanchang, 330008, Jiangxi Province, People's Republic of China
| | - Yaqin Huang
- Department of Gastroenterology, Third Affiliated Hospital of Nanchang University, Nanchang, 330008, Jiangxi Province, People's Republic of China
| | - Li Zheng
- Department of Gastroenterology, Third Affiliated Hospital of Nanchang University, Nanchang, 330008, Jiangxi Province, People's Republic of China
| | - Nian Fang
- Department of Gastroenterology, Third Affiliated Hospital of Nanchang University, Nanchang, 330008, Jiangxi Province, People's Republic of China
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Peraldo-Neia C, Ostano P, Mello-Grand M, Guana F, Gregnanin I, Boschi D, Oliaro-Bosso S, Pippione AC, Carenzo A, De Cecco L, Cavalieri S, Micali A, Perrone F, Averono G, Bagnasacco P, Dosdegani R, Masini L, Krengli M, Aluffi-Valletti P, Valente G, Chiorino G. AKR1C3 is a biomarker and druggable target for oropharyngeal tumors. Cell Oncol (Dordr) 2020; 44:357-372. [PMID: 33211282 DOI: 10.1007/s13402-020-00571-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/21/2020] [Indexed: 10/22/2022] Open
Abstract
PURPOSE Oropharynx squamous cell carcinoma (OPSCC) is a subtype of head and neck squamous cell carcinoma (HNSCC) arising from the base of the tongue, lingual tonsils, tonsils, oropharynx or pharynx. The majority of HPV-positive OPSCCs has a good prognosis, but a fraction of them has a poor prognosis, similar to HPV-negative OPSCCs. An in-depth understanding of the molecular mechanisms underlying OPSCC is mandatory for the identification of novel prognostic biomarkers and/or novel therapeutic targets. METHODS 14 HPV-positive and 15 HPV-negative OPSCCs with 5-year follow-up information were subjected to gene expression profiling and, subsequently, compared to three extensive published OPSCC cohorts to define robust biomarkers for HPV-negative lesions. Validation of Aldo-keto-reductases 1C3 (AKR1C3) by qRT-PCR was carried out on an independent cohort (n = 111) of OPSCC cases. In addition, OPSCC cell lines Fadu and Cal-27 were treated with Cisplatin and/or specific AKR1C3 inhibitors to assess their (combined) therapeutic effects. RESULTS Gene set enrichment analysis (GSEA) on the four datasets revealed that the genes down-regulated in HPV-negative samples were mainly involved in immune system, whereas those up-regulated mainly in glutathione derivative biosynthetic and xenobiotic metabolic processes. A panel of 30 robust HPV-associated transcripts was identified, with AKR1C3 as top-overexpressed transcript in HPV-negative samples. AKR1C3 expression in 111 independent OPSCC cases positively correlated with a worse survival, both in the entire cohort and in HPV-positive samples. Pretreatment with a selective AKR1C3 inhibitor potentiated the effect of Cisplatin in OPSCC cells exhibiting higher basal AKR1C3 expression levels. CONCLUSIONS We identified AKR1C3 as a potential prognostic biomarker in OPSCC and as a potential drug target whose inhibition can potentiate the effect of Cisplatin.
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Affiliation(s)
- Caterina Peraldo-Neia
- Laboratory of Cancer Genomics, Fondazione Edo ed Elvo Tempia, via Malta 3, 13900, Biella, Italy
| | - Paola Ostano
- Laboratory of Cancer Genomics, Fondazione Edo ed Elvo Tempia, via Malta 3, 13900, Biella, Italy
| | - Maurizia Mello-Grand
- Laboratory of Cancer Genomics, Fondazione Edo ed Elvo Tempia, via Malta 3, 13900, Biella, Italy
| | - Francesca Guana
- Laboratory of Cancer Genomics, Fondazione Edo ed Elvo Tempia, via Malta 3, 13900, Biella, Italy
| | - Ilaria Gregnanin
- Laboratory of Cancer Genomics, Fondazione Edo ed Elvo Tempia, via Malta 3, 13900, Biella, Italy
| | - Donatella Boschi
- Department of Drug Science and Technology, University of Turin, via Pietro Giuria 9, 10125, Turin, Italy
| | - Simonetta Oliaro-Bosso
- Department of Drug Science and Technology, University of Turin, via Pietro Giuria 9, 10125, Turin, Italy
| | - Agnese Chiara Pippione
- Department of Drug Science and Technology, University of Turin, via Pietro Giuria 9, 10125, Turin, Italy
| | - Andrea Carenzo
- Integrated Biology Platform, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy
| | - Loris De Cecco
- Integrated Biology Platform, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy
| | - Stefano Cavalieri
- Head and Neck Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, via Venezian 1, 20133, Milan, Italy
| | - Arianna Micali
- Integrated Biology Platform, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy
| | - Federica Perrone
- Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, via Venezian 1, 20133, Milan, Italy
| | - Gianluca Averono
- Otorhinolaryngology Unit, Ospedale degli Infermi, via dei Ponderanesi 1, Ponderano, Biella, Italy
| | - Paolo Bagnasacco
- Otorhinolaryngology Unit, Ospedale degli Infermi, via dei Ponderanesi 1, Ponderano, Biella, Italy
| | | | - Laura Masini
- Department of Translational Medicine, UPO School of Medicine, Radiotherapy Unit, Novara, Italy
| | - Marco Krengli
- Department of Translational Medicine, UPO School of Medicine, Radiotherapy Unit, Novara, Italy
| | - Paolo Aluffi-Valletti
- Department of Health Sciences, UPO School of Medicine, Otorhinolaryngology Unit, Novara, Italy
| | - Guido Valente
- Department of Translational Medicine, UPO School of Medicine, Radiotherapy Unit, Novara, Italy
| | - Giovanna Chiorino
- Laboratory of Cancer Genomics, Fondazione Edo ed Elvo Tempia, via Malta 3, 13900, Biella, Italy.
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Deng Y, Zheng X, Zhang Y, Xu M, Ye C, Lin M, Pan J, Xu Z, Lu X, Chi P. High SPRR1A expression is associated with poor survival in patients with colon cancer. Oncol Lett 2020; 19:3417-3424. [PMID: 32269614 PMCID: PMC7115157 DOI: 10.3892/ol.2020.11453] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2019] [Accepted: 11/07/2019] [Indexed: 12/24/2022] Open
Abstract
High expression of small proline-rich protein 1A (SPRR1A) has been shown to be associated with tumor prognosis; however, the association between SPRR1A expression and colon cancer prognosis remains unclear. The present study sought to evaluate the association between SPRR1A expression and the clinicopathological characteristics of colon cancer, and to examine its potential prognostic value. A total of 114 patients with colon cancer were included. SPRR1A expression was evaluated by immunohistochemical staining, and the association between SPRR1A expression and clinicopathological parameters was analyzed. The prognostic value of SPRR1A was analyzed by Cox regression analysis, the Oncomine database and the R2 platform. SPRR1A expression was significantly increased in cancerous tissues compared with that in adjacent non-cancerous tissues. SPPRR1A expression was significantly associated with lymph node invasion. High SPRR1A expression was significantly associated with worse overall and disease-free survival rate. Cox regression analysis revealed that T stage, pathological N stage and high SPRR1A expression remained independent predictors for overall survival rate. The Oncomine database analysis demonstrated that SPRR1A mRNA expression levels were significantly increased in colorectal cancer tissues compared with those in adjacent non-cancerous tissues, and high SPRR1A expression was associated with a significantly worse event- and relapse-free survival time in the R2 platform. The data indicate that SPRR1A may serve as a potential biomarker for the prognosis of colon cancer.
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Affiliation(s)
- Yu Deng
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Xin Zheng
- Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Yiyi Zhang
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Meifang Xu
- Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Chengwei Ye
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Mengxin Lin
- Department of Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Jie Pan
- Department of Emergency Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Zongbin Xu
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Xingrong Lu
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Pan Chi
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
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Comprehensive Analysis of the Expression and Prognosis for GBPs in Head and neck squamous cell carcinoma. Sci Rep 2020; 10:6085. [PMID: 32269280 PMCID: PMC7142114 DOI: 10.1038/s41598-020-63246-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2019] [Accepted: 03/23/2020] [Indexed: 12/14/2022] Open
Abstract
Guanylate binding proteins (GBPs) belongs to the interferons (IFNs) induced guanylate-binding protein family (Guanosine triphosphatases, GTPases) consisting of seven homologous members, termed GBP1 to GBP7. We used multidimensional survey ways to explore GBPs expression, regulation, mutations, immune infiltration and functional networks in head and neck squamous cell carcinoma (HNSCC) patient data based on various open databases. The study provides staggered evidence for the significance of GBPs in HNSCC and its potential role as a novel biomarker. Our results showed that over expressions of 7 GBPs members and multivariate analysis suggested that N-stage, high expressions of GBP1 and low expression of GBP6/7 were linked to shorter OS in HNSCC patients. In addition, B cells of immune infiltrates stimulant the prognosis and might have a medical prognostic significance linked to GBPs in HNSCC. We assume that GBPs play a synergistic role in the viral related HNSCC. Our results show that data mining efficiently reveals information about GBPs expression in HNSCC and more importance lays a foundation for further research on the role of GBPs in cancers.
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