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BACKGROUND: Increased prevalence of hepatocellular carcinoma (HCC) remains a global health challenge. HCC chemoresistance is a clinical obstacle for its management. Aberrant miRNA expression is a hallmark for both cancer progression and drug resistance. However, it is unclear which miRNAs are involved in HCC chemoresistance. METHODS: MicroRNA microarray analysis revealed a differential expression profile of microRNAs between the hepatocellular carcinoma HA22T cell line and the HDACi-R cell line, which was validated by quantitative real-time PCR (qRT-PCR). To determine the biological function of miR-342-5p and the mechanism of the microRNA-342-5p/CFL1 axis in hepatocellular carcinoma HDACi resistance, loss- and gain-of-function studies were conducted in vitro. RESULTS: Here we demonstrated the molecular mechanism of histone deacetylase inhibitor (HDACi) resistance in HCC. Differential miRNA expression analysis showed significant down regulation of miR-342-5p in HDACi-R cells than in parental HA22T cells. Mimics of miR-342-5p enhanced apoptosis through upregulation of Bax, cyto-C, cleaved-caspase-3 expressions with concomitant decline in anti-apoptotic protein (Bcl-2) in HDACi-R cells. Although HDACi did not increase cell viability of HDACi-R, overexpression of miR-342-5p decreased cofilin-1 expression, upregulated reactive oxygen species (ROS) mediated apoptosis, and sensitized HDACi-R to HDACi in a dose-dependent manner. CONCLUSION: Our findings demonstrated the critical role of miR-342-5p in HDACi resistance of HCC and that this mechanism might be attributed to miR-342-5p/cofilin-1 regulation.
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Bladder cancer stands as a prevailing neoplasm among men globally, distinguished for its pronounced malignancy attributed to invasiveness and metastatic proclivity. Tannic acid (TA), an organic compound in many plants, has garnered recent attention for its discernible anti-mutagenic attributes. This investigation endeavored to scrutinize the repercussions of TA on grade II bladder cancer, with a concerted focus on unraveling its anti-cancer mechanisms. The cytotoxic effects of TA on grade II bladder cancer cells were investigated using multiple techniques, including MTT assay, flow cytometry, TUNEL assay, and western blot. Our findings revealed that elevated concentrations of TA induced cytotoxic effects in grade II bladder cancer cells. Both flow cytometry and the TUNEL assay substantiated the dose-dependent capacity of TA to prompt apoptosis. Western blot analysis corroborated that TA treatment in bladder cancer cells resulted in the upregulation of cleaved caspase-3 expression and PARP. Furthermore, heightened TA dosage elicited an augmentation in the expression of pro-apoptotic proteins, namely Bax and Bak, alongside a reduction in the expression of the anti-apoptotic protein Bcl-2 within bladder cancer cells. This study confirms TA as a potential anticancer agent, demonstrably diminishing the viability of bladder cancer cells. TA exerts cytotoxicity through the activation of mitochondrial apoptotic pathways. Specifically, TA initiates the cleavage of PARP and caspase-3, concurrently augmenting the expression of pro-apoptotic proteins to facilitate apoptosis. Collectively, the present study indicates that TA effectively impedes the proliferation of bladder cancer cells by instigating apoptosis through the intrinsic mitochondrial pathway.
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Apoptosis , Proliferación Celular , Mitocondrias , Taninos , Neoplasias de la Vejiga Urinaria , Humanos , Taninos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Caspasa 3/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Poli(ADP-Ribosa) Polimerasas/metabolismo , PolifenolesRESUMEN
Aberrant expression of UNC13C (Unc-13 Homolog C) has been observed during the progression of oral squamous cell carcinoma. However, the expression pattern and clinical relevance of UNC13C in Hepatocellular carcinoma (HCC) remain to be elucidated. The purpose of this study is to examine UNC13C expression in HCC and explore its role in clinicopathological factor or prognosis in HCC. Two hundred and sixty-five patients diagnosed with HCC were included in the present study. The expression of UNC13C in HCC tissues was analyzed by immunohistochemistry analysis. The relationship between UNC13C protein and clinicopathological characteristics in HCC was investigated. Moreover, the high expression of UNC13C was significantly correlated with T stage, AJCC stage and overall survival rates. Cox regression analysis identified UNC13C as an independent prognostic indicator for HCC patients. UNC13C might be a prognostic biomarker and therapeutic target in HCC. Further studies with larger sample sets are needed to understand the clinical implications of UNC13C in hepatocellular carcinoma.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma de Células Escamosas , Neoplasias Hepáticas/diagnóstico , Neoplasias de la Boca , PronósticoRESUMEN
Lung cancer is the major cause of cancer associated mortality. Mutations in EGFR have been implicated in lung cancer pathogenesis. Gefitinib (GF) is a RTKI (receptor tyrosine kinase inhibitor) first-choice drug for EGFR mutated advanced lung cancer. However, drug toxicity and cancer cell resistance lead to treatment failure. Consequently, new therapeutic strategies are urgently required. Therefore, this study was aimed at identifying tumor suppressive compounds that can synergistically improve Gefitinib chemosensitivity in the lung cancer treatment. Medicinal plants offer a vast platform for the development of novel anticancer agents. Daidzein (DZ) is an isoflavone compound extracted from soy plants and has been shown to possess many medicinal benefits. The anticancer potential of GF and DZ combination treatment was investigated using MTT, western blot, fluorescent microscopy imaging, flow cytometry and nude mice tumor xenograft techniques. Our results demonstrate that DZ synergistically induces c-Jun nuclear translocation through ROS/ASK1/JNK and downregulates EGFR-STAT/AKT/ERK pathways to activate apoptosis and a G0/G1 phase cell cycle blockade. In in-vivo, the combination treatment significantly suppressed A549 lung cancer cells tumor xenograft growth without noticeable toxicity. Daidzein supplements with current chemotherapeutic agents may well be an alternative strategy to improve the treatment efficacy of lung adenocarcinoma.
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Adenocarcinoma del Pulmón , Antineoplásicos , Isoflavonas , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/tratamiento farmacológico , Animales , Antineoplásicos/farmacología , Apoptosis , Línea Celular Tumoral , Resistencia a Antineoplásicos/genética , Receptores ErbB/genética , Gefitinib/farmacología , Gefitinib/uso terapéutico , Humanos , Isoflavonas/farmacología , Isoflavonas/uso terapéutico , Neoplasias Pulmonares/genética , Sistema de Señalización de MAP Quinasas , Ratones , Ratones Desnudos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de OxígenoRESUMEN
Background and Objectives: Kruppel-like factor 10 (KLF10) participates in the tumorigenesis of several human cancers by binding to the GC-rich region within the promoter regions of specific genes. KLF10 is downregulated in human cancers. However, the role of KLF10 in gastric cancer formation remains unclear. Materials and Methods: In this study, we performed immunohistochemical staining for KLF10 expression in 121 gastric cancer sections. Results: The loss of KLF10 expression was correlated with advanced stages and T status. Kaplan-Meier analysis revealed that patients with higher KLF10 levels had longer overall survival than those with lower KLF10 levels. Univariate analysis revealed that in patients with gastric cancer, advanced stages and low KLF10 levels were associated with survival. Multivariate analysis indicated that age, gender, advanced stages, and KLF10 expression were independent prognostic factors of the survival of patients with gastric cancer. After adjusting for age, gender, and stage, KLF10 expression was also found to be an independent prognostic factor in the survival of patients with gastric cancer. Conclusion: Our results collectively suggested that KLF10 may play a critical role in gastric cancer formation and is an independent prognosis factor of gastric cancer.
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Factores de Transcripción de la Respuesta de Crecimiento Precoz , Neoplasias Gástricas , Transformación Celular Neoplásica , Factores de Transcripción de la Respuesta de Crecimiento Precoz/genética , Factores de Transcripción de la Respuesta de Crecimiento Precoz/metabolismo , Humanos , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Pronóstico , Neoplasias Gástricas/genéticaRESUMEN
BACKGROUND/AIM: Metastasis-associated protein 1 (MTA1) plays a role in ATP-dependent nucleosome disruption activity and histone deacetylase activity and may indicate DNA methylation activity. MTA1 may also be involved in the progression of oral squamous cell carcinoma (OSCC). PATIENTS AND METHODS: MTA1 immunoreactivity was analyzed using immunohistochemical (IHC) staining analysis in specimens from 281 OSCC patients. Kaplan-Meier analysis was used to determine the prognostic value of MTA1 for overall survival. RESULTS: High MTA1 expression was significantly associated with female gender and lymph node metastasis. Multivariate analyses showed the independent prognostic role of high MTA1 expression in patients with OSCC of poorer mean survival. CONCLUSION: MTA1 expression, detected by IHC staining, could be an independent prognostic marker for patients of OSCC.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Femenino , Histona Desacetilasas/genética , Humanos , Neoplasias de la Boca/genética , Pronóstico , Proteínas Represoras/genética , Carcinoma de Células Escamosas de Cabeza y Cuello , TransactivadoresRESUMEN
BACKGROUND/AIM: To investigate the impact of PDZ-binding kinase (PBK) on the clinical outcome of patients with oral squamous cell carcinoma (OSCC) who received radiotherapy. PATIENTS AND METHODS: PBK immunoreactivity of cancer specimens obtained from 179 patients with primary OSCC was analyzed by immunohistochemistry. RESULTS: High PBK expression in tumor cells tended to be associated with advanced N-stage. The 5-year survival rate was greater for patients with high total PBK expression than in those with low PBK expression. After adjustment, high PBK remained associated with a favorable outcome. In subgroups according to tumor stage, the prognostic role was significant in patients with stage III/IV rather than those with stage I/II disease. CONCLUSION: We suggest that PBK expression should be used as an independent prognostic marker for patients with OSCC treated with radiotherapy, especially for those with advanced-stage disease.
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Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/radioterapia , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/radioterapia , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Inmunohistoquímica , Estilo de Vida , Masculino , Persona de Mediana Edad , Quinasas de Proteína Quinasa Activadas por Mitógenos/fisiología , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Análisis de Supervivencia , Taiwán/epidemiologíaRESUMEN
Background and Objectives: Oral squamous cell carcinoma (OSCC) is a malignant disease with a particularly high incidence in Taiwan. Our objective in this study was to elucidate the involvement of sphingolipid transporter 2 (SPNS2) expression and SPNS2 protein expression in the clinicopathological indexes and the clinical outcomes of OSCC patients. Materials and Methods: Immunohistochemistry analysis was performed for SPNS2 protein expression in samples from 264 cases of OSCC. Correlations of SPNS2 expression with clinicopathological variables and patient survival were analyzed. Results: Our results revealed that the cytoplasmic protein expression of SPNS2 in OSCC tissue specimens was lower than in normal tissue specimens. Negative cytoplasmic protein expression of SPNS2 was significantly correlated with T status and stage. Kaplan-Meier survival curve analysis revealed that negative cytoplasmic SPNS2 expression was predictive of poorer overall survival of OSCC patients in stage III/IV. We also determined that low SPNS2 expression was an independent prognostic factor related to overall survival among OSCC patients in stage III/IV from univariate Cox proportional hazard models. Multivariate Cox proportional hazard models revealed that cytoplasmic SPNS2 expression, T status, lymph node metastasis, and histological grade were independent prognostic factors for survival. Conclusions: Overall, this study determined that SPNS2 protein may be a useful prognostic marker for OSCC patients and potential therapeutic target for OSCC treatment.
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Proteínas de Transporte de Anión , Neoplasias de la Boca , Carcinoma de Células Escamosas de Cabeza y Cuello , Biomarcadores de Tumor , Humanos , Pronóstico , TaiwánRESUMEN
BACKGROUND/AIM: To characterize the potential roles of CEP55 in colorectal cancer development and assess its eligibility as a prognostic diagnosis tool for colorectal cancer. PATIENTS AND METHODS: Immunohistochemical (IHC) analysis of CEP55 immunoreactivity in 166 cancer specimens from colorectal cancer patients. RESULTS: CEP55 was not found to statistically significantly affect different patient clinical parameters. Multivariate analysis illustrated that patients with N stage (1+2) colorectal cancer and high CEP55 expression had a significantly lower five-year survival rate than patients with N stage (1+2) colorectal cancer and low CEP55 expression. CONCLUSION: There is a correlation between CEP55 and advanced N-stage colorectal cancer. Thus, CEP55 may be a potential diagnostic biomarker for colorectal cancer patients.
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Biomarcadores de Tumor , Proteínas de Ciclo Celular/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Expresión Génica , Anciano , Anciano de 80 o más Años , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Neoplasias Colorrectales/patología , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , PronósticoRESUMEN
BACKGROUND AND OBJECTIVES: Krüppel-like transcription factor 10 (KLF10) plays a vital role in regulating cell proliferation, including the anti-proliferative process, activation of apoptosis, and differentiation control. KLF10 may also act as a protective factor against oral cancer. We studied the impact of KLF10 expression on the clinical outcomes of oral cancer patients to identify its role as a prognostic factor in oral cancer. MATERIALS AND METHODS: KLF10 immunoreactivity was analyzed by immunohistochemical (IHC) stain analysis in 286 cancer specimens from primary oral cancer patients. The prognostic value of KLF10 on overall survival was determined by Kaplan-Meier analysis and the Cox proportional hazard model. RESULTS: High KLF10 expression was significantly associated with male gender and betel quid chewing. The 5-year survival rate was greater for patients with high KLF10 expression than for those with low KLF10 expression (62.5% vs. 51.3%, respectively; p = 0.005), and multivariate analyses showed that high KLF10 expression was the only independent factor correlated with greater overall patient survival. The significant correlation between high KLF10 expression and a higher 5-year survival rate was observed in certain subgroups of clinical parameters, including female gender, non-smokers, cancer stage T1, and cancer stage N0. CONCLUSIONS: KLF10 expression, detected by IHC staining, could be an independent prognostic marker for oral cancer patients.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Factores de Transcripción de la Respuesta de Crecimiento Precoz , Femenino , Humanos , Factores de Transcripción de Tipo Kruppel/genética , Masculino , Neoplasias de la Boca/genética , Pronóstico , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
BACKGROUND/AIM: Casein kinase 1 epsilon (CK1ε) is a member of the casein kinase 1 family, which includes highly conserved and ubiquitous serine/threonine protein kinases. Recent research has revealed that CK1ε plays an important role in a variety of human cancer types; however, its role in human melanoma remains unclear. The aim of this study was to elucidate the clinical role of CK1ε in patients with melanoma. PATIENTS AND METHODS: Samples from 34 patients with melanoma were analyzed by immunohistochemical staining. Formalin-fixed paraffin-embedded tissue microarrays were also examined by two histopathologists to assess CK1ε protein expression in humans. RESULTS: Cytoplasmic CK1ε protein expression was significantly lower in tumor tissue than in normal tissue. Lack of cytoplasmic CK1ε protein was significantly correlated with distant metastasis (p=0.022) and poorer survival (p=0.030). However, Kaplan-Meier survival analysis revealed that elevated expression of cytoplasmic CK1ε protein was not significantly associated with the overall survival of patients with melanoma. Univariate and multivariate analyses demonstrated that lack of cytoplasmic CK1ε protein expression was related to distant metastasis (p<0.001 and p=0.004), showing that CK1ε was a prognostic factor. CONCLUSION: CK1ε protein expression might serve as a prognostic indicator in the treatment of patients with melanoma.
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Caseína Cinasa 1 épsilon , Melanoma , Biomarcadores de Tumor/genética , Citoplasma , Humanos , Estimación de Kaplan-Meier , Melanoma/genética , PronósticoRESUMEN
Oral squamous cell carcinoma (OSCC) is the most common epithelial malignancy affecting the oral cavity, and it is especially significant in Asian countries. Patients diagnosed with OSCC have an unfavorable prognosis and additional prognostic markers would help improve therapeutic strategies. We sought to investigate the association between eukaryotic translation initiation factor 5A2 (EIF5A2) and epithelial-mesenchymal transition (EMT) markers as well as the prognostic significance of EIF5A2 in OSCC. The expression of EIF5A2 and EMT markers was measured through the immunohistochemical staining of specimens from 272 patients with OSCC. In addition, the correlation between different clinicopathological factors and EIF5A2 expression was analyzed. The prognostic role of EIF5A2 was then analyzed via Kaplan-Meier analysis and Cox proportional hazard models. Among the 272 patients, high EIF5A2 expression was significantly associated with an advanced N value (p = 0.008). High tumor expression of EIF5A2 was prone to the expression of low E-cadherin and high beta-catenin (p = 0.046 and p = 0.020, respectively). Patients with high EIF5A2 expression had unfavorable five-year survival rates as compared with those with low expression (49.7% and 67.3%, respectively). The prognostic role of EIF5A2 was further confirmed through multivariate analysis (hazard ratio = 1.714, 95% confidence interval: 1.134-2.590, p = 0.011). High EIF5A2 expression is associated with an advanced N value and EMT markers and may serve as a marker for an unfavorable prognosis in patients with OSCC.
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BACKGROUND/AIM: Glycogen synthase kinase 3 beta (GSK3-ß) acts either as a tumor suppressor or an oncogene in various human cancers. The present study aimed to investigate the expression and activity of p-GSK3-ß (Ser9) in oral cancer patients. MATERIALS AND METHODS: We investigated the levels of p-GSK3ß in 152 oral cancer tissues by immunohistochemistry, and explored their prognostic impact. RESULTS: To investigate the role of p-GSK3ß (Ser9) in OSCC progression, we first analyzed the expression levels of protein p-GSK3ß in normal and oral cancer tissues using immunohistochemical staining. p-GSK3ß immunostaining was detected in 32 of 152 (21.1%) oral cancer specimens. High p-GSK3ß expression was significantly associated with T (III/IV) stage. Kaplan-Meier survival analysis revealed that high levels of p-GSK3ß were correlated with poor survival (p=0.001) in T stage (III/IV) OSCC patients. Multivariate analyses indicated that TN stage, AJCC tumor stage, tumor differentiation status and clinical therapy, but not p-GSK3ß levels, were independent prognostic factors. Significant mortality risk was found in T stage (III/IV) oral cancer patients with high levels of p-GSK3ß (p=0.0006). CONCLUSION: GSK3ß inactivation is a key event in oral cancer patients and targeting GSK3ß might be valuable in treating oral cancer patients.
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Carcinoma de Células Escamosas , Neoplasias de la Boca , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Glucógeno Sintasa Quinasa 3 , Glucógeno Sintasa Quinasa 3 beta/genética , Humanos , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Estadificación de Neoplasias , PronósticoRESUMEN
BACKGROUND AND OBJECTIVES: Patients with oral squamous cell carcinoma (OSCC), a common malignancy in Asian countries, have a poor prognosis. We investigated the role of Krüppel-like factor 17 (KLF17) and its prognostic significance in OSCC. MATERIALS AND METHODS: KLF17 expression was measured by immunohistochemical staining of specimens from 283 patients with OSCC. We analyzed correlations between KLF17 expression and clinicopathologic features and between KLF17 expression and overall survival. The prognostic value of KLF17 was tested using Kaplan-Meier analysis and Cox proportional hazard models. RESULTS: Among the 283 patients, high KLF17 expression was significantly associated with an early OSCC stage and low T-value (p = 0.033 and p = 0.036, respectively). The five-year survival rates were better in patients with high KLF17 expression than with low expression (66.5% and 49.6%, respectively). The prognostic role of KLF17 was further confirmed through multivariate analysis (hazard ratio 1.506, 95% confidence interval 1.034-2.191, p = 0.033). The prognostic value was more significant in patients with a history of betel quid chewing or with a low T-value. CONCLUSIONS: High KLF17 expression can serve as a marker for a favorable prognosis in patients with OSCC. The prognostic role of KLF17 is more significant in patients with a history of betel quid chewing or a low T-value.
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Carcinoma de Células Escamosas/química , Neoplasias de la Boca/química , Proteínas de Neoplasias/análisis , Factores de Transcripción/análisis , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Intervalos de Confianza , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Potential function of UNC13C in variety of cancers including, oral squamous cell carcinoma (OSCC) remains obscure. In the present study, immunohistochemical staining in tissue microarrays containing 268 OSCC samples showed that UNC13C protein levels were inversely correlated with AJCC Stage III and IV (P = 0.002) and death (P = 0.0134). Patients with lower UNC13C expression had a significantly shorter survival (P = 0.0231) than those with higher UNC13C expression. We also identified decreased overall UNC13C expression in oral cancer cell lines. In addition, our functional analysis of UNC13C shows that overexpression of UNC13C inhibited migration and invasion capacities of SCC-9 and SAS cells compared with the empty plasmid transfected cells. Further experiments suggested that transcription factors (Slug, Snail, Twist, and ZEB1) and mesenchymal marker (Vimentin) were down regulated and Tight Junction Protein (Claudin1) was up regulated after UNC13C overexpression in SCC9 and SAS cells. The novel role of UNC13C is revealed for the first time in OSCC. In summary, these results suggest that UNC13C as a novel tumor suppressor and an essential regulator of EMT signaling pathway during OSCC progression, and thus it could be used as a target for preventing oral cancer metastasis.
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Prostate cancer (PCa) is a common malignancy in males and has a relatively slower progression than other cancers. Our goal was to evaluate the clinical role of SPARC (secreted protein acidic and cysteine rich, osteonectin), cwcv, and kazal-like domains' proteoglycan 1 (SPOCK1) in PCa. SPOCK1 expression was studied through the immunohistochemical staining of specimens from 71 patients with PCa. The correlation between SPOCK1 expression and clinicopathological features was quantitatively analyzed. We used Kaplan-Meier analysis and Cox proportional hazard models to analyze the prognostic value. Of 71 PCa patients, high SPOCK1 expression was more likely to be seen in those with an advanced stage (p = 0.018) of the disease and an advanced tumor (T) value (p = 0.014). Patients in Gleason grade groups 3 and 4 had significantly higher SPOCK1 expression (p = 0.044 and 0.003, respectively) compared to those of Gleason grade group 1. However, this trend was not observed in patients in Gleason grade group 5. For the survival analysis, although it was not statistically significant, patients with a high SPOCK1 expression had a shorter median overall survival (6.2 years) compared to those with low expression (7.8 years). High SPOCK1 expression may be related to advanced clinicopathological features and possibly a poor prognosis. Further analysis with a larger patient base would help clarify this issue.
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Neoplasias de la Próstata/clasificación , Proteoglicanos/análisis , Anciano , Expresión Génica/genética , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias/métodos , Pronóstico , Neoplasias de la Próstata/sangre , Proteoglicanos/sangre , Análisis de SupervivenciaRESUMEN
BACKGROUND: Discoidin domain receptors (DDRs), a collagen receptor tyrosine kinase, play a major role in cancer progression. DDR2 has been suggested as a prognostic marker in several cancer types; however, the correlation between DDR2 expression and clinical outcome of oral cancer patients in Taiwan population has not been investigated. MATERIALS AND METHODS: In the present study we sought to determine the clinical significance of Discoidin Domain Receptor Tyrosine Kinase 2 (DDR2) expression in oral squamous cell carcinoma (OSCC) patients. We examined DDR2 expression in OSCC specimens by immunohistochemistry and then we analyzed the association of DDR2 expression with clinicopathological factors in OSCC. RESULTS: We divided 254 OSCC cases into two groups based on DDR2 expression levels and compared with several clinicopathological factors and their overall survival. The group with high DDR2 expression had significantly higher frequencies of lymph node metastasis (P= 0.0094) and AJCC stage (P= 0.0058) compared to the group with low DDR2 expression. Furthermore, the lymph node metastasis oral cancer patients with high DDR2 expression had low survival rate than low DDR2 group (P= 0.0458). CONCLUSIONS: Our data indicate that DDR2 is a potent biomarker that can be used as an effective therapeutic target for treating OSCC patients with lymph node metastasis.
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Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Receptor con Dominio Discoidina 2/genética , Neoplasias de la Boca/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patologíaRESUMEN
OBJECTIVE: Lung adenocarcinoma is a non-small cell lung cancer, a common cancer in both genders, and has poor clinical outcome. Our aim was to evaluate the role of epidermal growth factor (EGF)-like domain multiple 6 (EGFL6) and its prognostic significance in lung adenocarcinoma. METHODS: EGFL6 expression was studied by immunohistochemical staining of specimens from 150 patients with lung adenocarcinoma. The correlation between clinicopathological features and EGFL6 expression was quantitatively analysed. We used Kaplan-Meier analysis and Cox proportional hazard models to examine the prognostic value of EGFL6 in terms of overall survival. RESULTS: No significant correlation was found between EGFL6 expression and clinical parameters. However, patients with high levels of EGFL6 expression showed a tendency towards poor prognosis, with borderline statistical significance. Grouping the patients according to a medium age value revealed a significant association between high EGFL6 expression and poor clinical outcome in young patients. This finding was further confirmed by grouping the patients into three groups according to age. HR in patients with high EGFL6 expression was higher in younger patients than in older patients. CONCLUSION: High EGFL6 expression may serve as a marker for poor prognosis of lung adenocarcinoma, especially in younger patients.
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Adenocarcinoma/genética , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Glicoproteínas de Membrana/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Anciano , Proteínas de Unión al Calcio , Moléculas de Adhesión Celular , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Taiwán/epidemiologíaRESUMEN
INTRODUCTION: Squamous cell carcinoma is the most common cancer of the oral cavity. In spite of advancements in surgical, chemoradiological and targeted therapies, these therapeutic strategies still have had little impact on survival rates. X-box binding protein-1 (XBP-1) is a potent transcription factor that is involved in the unfolded protein response (UPR) pathway, which itself is activated in response to endoplasmic reticulum stress as a method to restore cellular homeostasis. The role XBP-1 plays in oral squamous cell carcinoma (OSCC) has yet to be determined. In this study, we used molecular and immunohistochemical analyses to investigate the role of XBP-1 protein playing in the OSCC carcinogenesis. MATERIALS AND METHODS: We used immunohistochemical analyses to investigate XBP-1 expression in 255 OSCC tissue specimens, as well as migration and invasion assays with XBP-1 siRNA transfection of oral cancer cell lines to confirm its role in OSCC. RESULTS: The XBP-1 immunostaining was dichotomized as low-level expression and high-level expression. We found that low-level cytoplasmic XBP-1expression was significantly correlated with larger tumor size (p=0.047), more advanced clinical stage (p<0.0001), lymph node metastasis (p=0.002), and shorter overall survival (p=0.011). Kaplan-Meier survival curves showed that low-level cytoplasmic XBP-1 expression was significantly correlated with shorter overall survival (p=0.031). The univariate Cox regression analysis revealed that cytoplasmic XBP-1 expression was a prognostic factor for overall survival of patients with OSCC. We also found that inhibition of XBP-1 promoted OSCC cell migration and invasion. CONCLUSION: Our results suggest that XBP-1 expression may play an essential role in the pathogenesis of OSCC and that targeting XBP-1 may be a sound therapeutic strategy.