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1.
Front Oncol ; 11: 655071, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34307131

RESUMEN

BACKGROUND: Sarcopenia has been associated with treatment-related toxicities and poor survival in cancer patients. Our aim was to investigate the prevalence of sarcopenia in postoperative recurrent esophageal squamous cell carcinoma (ESCC) patients receiving chemoradiotherapy (CRT) and evaluate associations with treatment-related toxicity and prognosis. METHODS: One hundred and eighty-four patients with postoperative locoregional recurrent ESCC receiving CRT between January 2014 and December 2016 were included. The skeletal muscle area (SMA) was measured at the third lumbar vertebra level. Sarcopenia was defined as skeletal muscle index (SMI = SMA/height2) less than 47.24/cm2/m2 for men and 36.92/cm2/m2 for women. Association of sarcopenia with overall survival (OS) was analyzed using univariate and multivariate cox regression models. RESULTS: Sarcopenia was observed in 94 of 184 (51.1%) patients. Sarcopenic patients had significantly higher rates of grade 3-4 toxicities compared to those without sarcopenia (36.2% vs 21.1%, p = 0.034). The survival rate at 12 and 24 months was 36.2% and 3.2% in the sarcopenic patients and 57.8% and 17.8% in the non-sarcopenic patients (p < 0.001). Multivariate cox regression analysis showed that sarcopenia was significantly associated with decreased OS (HR = 1.729, 95% CI 1.231-2.428, p = 0.002). CONCLUSIONS: Sarcopenia is an independent indicator of poor survival in postoperative locoregional recurrent ESCC patients treated with CRT. Early nutritional interventions before treatment may improve the prognosis.

2.
Radiat Oncol ; 16(1): 94, 2021 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-34039375

RESUMEN

BACKGROUND: This retrospective study was to assess and compare the toxicity and efficacy of concurrent chemoradiotherapy (CCRT) with S-1 or docetaxel and cisplatin in patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Patients with locally advanced ESCC who received CCRT with S-1 (70 mg/m2 twice daily on days 1-14, every 3 weeks for 2 cycles, S-1 group) or docetaxel (25 mg/m2) and cisplatin (25 mg/m2) on day 1 weekly (DP group) between 2014 and 2016 were retrospectively analyzed. Radiotherapy was delivered in 1.8-2.0 Gy per fraction to a total dose of 50-60 Gy. Treatment-related toxicities (Common Terminology Criteria for Adverse Events version 4.0), response rate, and survival outcomes were compared between groups. RESULTS: A total of 175 patients were included in this study (72 in the S-1 group and 103 in the DP group). Baseline characteristics were well balanced between the two groups. The incidence of grade 3-4 adverse events were significantly lower in the S-1 group than that of the DP group (22.2% vs. 45.6%, p = 0.002). In the DP group, elderly patients (> 60 years) had a significantly higher rate of grade 3-4 adverse events than younger patients (58.1% vs. 31.3%, p = 0.01). The objective overall response rate (complete response + partial response) was 68.1% in the S-1 group, and 73.8% the DP group (p = 0.497). The 3-year overall survival was 34.7% in the S-1 group, and 38.8% in the DP group (p = 0.422). The 3-year progression free survival in the DP group was higher than that in the S-1 group but without significant difference (33.0% vs. 25.0%, p = 0.275). CONCLUSION: CCRT with S-1 is not inferior to CCRT with docetaxel and cisplatin and is better tolerated in in elderly patients with locally advanced ESCC.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/terapia , Anciano , Quimioradioterapia/efectos adversos , Quimioradioterapia/mortalidad , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Docetaxel/administración & dosificación , Docetaxel/efectos adversos , Fraccionamiento de la Dosis de Radiación , Combinación de Medicamentos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ácido Oxónico/administración & dosificación , Ácido Oxónico/efectos adversos , Estudios Retrospectivos , Tasa de Supervivencia , Tegafur/administración & dosificación , Tegafur/efectos adversos , Resultado del Tratamiento
3.
J Biochem ; 167(4): 365-370, 2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-31742336

RESUMEN

Aerobic glycolysis was closely associated with the malignant transformation and prognosis of tumours. miR-206 was found to be downregulated in several cancers. However, whether miR-206 functions in non-small-cell lung cancers (NSCLCs) via the process of aerobic glycolysis remains poorly characterized. Quantitative real-time PCR was performed to detect miR-206 level in NSCLC cells and tissues. The effect of miR-206 on hexokinase 2 (HK2) expression was examined through miR-206 overexpression or miR-206 knockdown. CCK-8 assay and colony formation assay were carried out to explore the role of miR-206 on cell proliferation and colony formation, respectively. The relationship between miR-206 and HK2 was measured by dual-luciferase reporter assay. Glucose consumption, lactate production assay and ATP generation were performed in NSCLC cells following miR-206 and HK2 overexpression. We found that miR-206 was downregulated in NSCLC tissues and cells. miR-206 overexpression downregulated the expression of HK2 via targeting HK2 3'UTR in NSCLC cells. In addition, miR-206 decreased the cell viability and colony formation in NSCLC cells. Furthermore, miR-206 reduced glucose uptake, lactate production and ATP generation in NSCLC cells via HK2 repression. In conclusion, these findings suggested that miR-206 regulated NSCLC cell aerobic glycolysis by targeting HK2.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Glucólisis , Hexoquinasa/metabolismo , Neoplasias Pulmonares/metabolismo , MicroARNs/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Células Cultivadas , Hexoquinasa/genética , Humanos , Neoplasias Pulmonares/patología , MicroARNs/genética
4.
Oncologist ; 24(8): e677-e686, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31040254

RESUMEN

BACKGROUND: Lymphopenia occurs commonly in esophageal squamous cell carcinoma (ESCC) and may influence treatment outcomes. We aimed to examine its association with treatment response and tumor progression in patients with locally advanced ESCC treated with concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: A total of 286 patients with stage II-IVa ESCC treated with CCRT between 2015 and 2017 were analyzed. Total lymphocyte counts were assessed at baseline, weekly, and 4 weeks after CCRT. Pretreatment lymphopenia was defined as total lymphocyte count <1,000 cells per mm3 at diagnosis, and treatment-related lymphopenia was defined as total lymphocyte count <200 cells per mm3 with 6 weeks after starting CCRT. Univariate and multivariate logistic regression methods were used to analyze factors associated treatment-related lymphopenia and treatment response. RESULTS: Lymphopenia was observed in 44 patients (15.4%) at initial diagnosis. Pretreatment lymphopenia was significantly associated with greater tumor length, worse T status, body mass index ≤18.5 kg/m2, and weight loss ≥3 kg in the previous 3 months. Six weeks after starting CCRT, 89 patients (31%) developed treatment-related lymphopenia. Tumor progression and cancer-related death were more frequently observed in treatment-related lymphopenia group than those without (76.4% vs. 52.8% and 58.4% vs. 39.6%). A complete response (CR) was achieved in 62 patients (21.7%). In multivariate analysis, treatment-related lymphopenia was significantly associated with lack of clinical CR, and older age, lower tumor location, greater tumor length, and larger planning target volume were independent predictors of treatment-related lymphopenia. CONCLUSION: Treatment-related lymphopenia during CCRT is an independent predictor for poor treatment response in ESCC. IMPLICATIONS FOR PRACTICE: A total of 286 patients with locally advanced esophageal squamous cell carcinoma were treated with concurrent chemoradiotherapy (CCRT), and treatment-related lymphopenia occurred in 31% of patients within 6 weeks from the start of CCRT. Treatment-related lymphopenia was significantly associated with lack of treatment response, and older age, lower tumor location, greater tumor length, and larger planning target volume were independent predictors of treatment-related lymphopenia. Lymphocyte count is an inexpensive biomarker that may be easily used by clinicians to identify patients who are most likely to benefit from CCRT.


Asunto(s)
Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/sangre , Carcinoma de Células Escamosas de Esófago/terapia , Linfopenia/patología , Desnutrición/sangre , Desnutrición/patología , Anciano , Quimioradioterapia , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
5.
Onco Targets Ther ; 11: 2333-2344, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29731641

RESUMEN

PURPOSE: Long noncoding RNAs (lncRNAs) are present in body fluids, but their potential as tumor biomarkers has never been investigated in malignant pleural effusion (MPE) caused by lung cancer. The aim of this study was to assess the clinical significance of lncRNAs in pleural effusion, which could potentially serve as diagnostic and predictive markers for lung cancer-associated MPE (LC-MPE). PATIENTS AND METHODS: RNAs from pleural effusion were extracted in 217 cases of LC-MPE and 132 cases of benign pleural effusion (BPE). Thirty-one lung cancer-associated lncRNAs were measured using quantitative real-time polymerase chain reaction (qRT-PCR). The level of carcinoembryonic antigen (CEA) was also determined. The receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were established to evaluate the sensitivity and specificity of the identified lncRNAs and other biomarkers. The correlations between baseline pleural effusion lncRNAs expression and response to chemotherapy were also analyzed. RESULTS: Three lncRNAs (MALAT1, H19, and CUDR) were found to have potential as diagnostic markers in LC-MPE. The AUCs for MALAT1, H19, CUDR, and CEA were 0.891, 0.783, 0.824, and 0.826, respectively. Using a logistic model, the combination of MALAT1 and CEA (AUC, 0.924) provided higher sensitivity and accuracy in predicting LC-MPE than CEA (AUC, 0.826) alone. Moreover, baseline MALAT1 expression in pleural fluid was inversely correlated with chemotherapy response in patients with LC-MPE. CONCLUSION: Pleural effusion lncRNAs were effective in differentiating LC-MPE from BPE. The combination of MALAT1 and CEA was more effective for LC-MPE diagnosis.

6.
J Transl Med ; 15(1): 221, 2017 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-29089030

RESUMEN

BACKGROUND: There is increasing evidence that the existence of systemic inflammation response is correlated with poor prognosis in several solid tumors. The aim of this retrospective study was to investigate the association between systemic immune-inflammation index (SII) and therapy response and overall survival in patients with stage III non-small cell lung cancer (NSCLC). The prognostic values of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and prognostic nutritional index (PNI) were also evaluated. METHODS: In total, 332 patients with new diagnosis of stage III NSCLC were included in this retrospective analysis. SII was defined as platelet counts × neutrophil counts/lymphocyte counts. Receiver operating characteristic (ROC) curve was used to evaluate the optimal cut-off value for SII, NLR, PLR and PNI. Univariate and multivariate survival analysis were performed to identify the factors correlated with overall survival. RESULTS: Applying cut-offs of ≥ 660 (SII), ≥ 3.57 (NLR), ≥ 147 (PLR), ≤ 52.95 (PNI), SII ≥ 660 was significantly correlated with worse ECOG PS (< 0.001), higher T stage (< 0.001), advanced clinical stage (p = 0.019), and lower response rate (p = 0.018). In univariate analysis, SII ≥ 660, NLR ≥ 3.57, PLR ≥ 147, and PNI ≤ 52.95 were significantly associated with worse overall survival (p all < 0.001). Patients with SII ≥ 660 had a median overall survival of 10 months, and patients with SII < 660 showed a median overall survival of 30 months. In multivariate analysis only ECOG PS (HR, 1.744; 95% CI 1.158-2.626; p = 0.008), T stage (HR, 1.332; 95% CI 1.032-1.718; p = 0.028), N stage (HR, 1.848; 95% CI 1.113-3.068; p = 0.018), SII (HR, 2.105; 95% CI 1.481-2.741; p < 0.001) and NLR ≥ 3.57 (HR, 1.934; 95% CI 1.448-2.585; p < 0.001) were independently correlated with overall survival. CONCLUSIONS: This study demonstrates that the SII is an independent prognostic indicator of poor outcomes for patients with stage III NSCLC and is superior to other inflammation-based factors in terms of prognostic ability.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia , Inflamación/inmunología , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/terapia , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Inflamación/patología , Estimación de Kaplan-Meier , Neoplasias Pulmonares/patología , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Neutrófilos/patología , Evaluación Nutricional , Recuento de Plaquetas , Curva ROC , Resultado del Tratamiento
7.
Sci Rep ; 7: 42581, 2017 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-28195186

RESUMEN

The present study evaluated the clinical and prognostic value of neutrophil-to-lymphocyte ratio (NLR) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (dCRT). A total of 517 patients with ESCC were enrolled and analysed retrospectively. The NLR was calculated at three time points: baseline, post-treatment, and at the time of tumor progression. Elevated NLR was defined as a ratio ≥5. High NLR at baseline was present in 204 (39%) patients and was significantly correlated with larger tumour size, advanced TNM stage, worse ECOG performance status, and dCRT response (p < 0.05). At a median follow-up of 17 months, patients with higher NLR at baseline had poorer progression-free survival (PFS) and overall survival (OS). On multivariate analysis, elevated NLR at baseline was independently associated with PFS and OS (HR = 1.529, p < 0.001 for PFS; HR = 1.856, p < 0.001 for OS). In addition, patients with high pre- and post-treatment NLR demonstrated worse clinical outcomes than other groups. Our results suggest that NLR is an independent prognostic indicator for patients with ESCC undergoing dCRT and changes in NLR level with treatment may indicate therapeutic benefit.


Asunto(s)
Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/mortalidad , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/mortalidad , Recuento de Leucocitos , Linfocitos , Neutrófilos , Adulto , Anciano , Biomarcadores , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Quimioradioterapia , Progresión de la Enfermedad , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago , Femenino , Estudios de Seguimiento , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Análisis de Supervivencia , Resultado del Tratamiento
8.
Mol Carcinog ; 55(12): 2095-2105, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-26756568

RESUMEN

To evaluate the clinical significance of lncRNAs in the resistance to cisplatin-based chemoradiotherapy in esophageal squamous cell carcinoma (ESCC). We focused on lncRNAs which were frequently reported in ESCC or were involved in chemoradiotherapy resistance. LncRNA expressions were examined in paired cisplatin-resistant and parental ESCC cell lines. Dysregulated lncRNAs were further measured in 162 pretreatment biopsy specimens of ESCC who received definitive chemoradiotherapy (dCRT). Then the correlations between lncRNA expression and response to dCRT and prognosis were analyzed. Three lncRNAs (AFAP1-AS1, UCA1, HOTAIR) were found to be deregulated in cisplatin-resistant cells compared with their parent cells. AFAP1-AS1 was significantly up-regulated in tumor tissues compared with adjacent normal tissues (P = 0.006). Furthermore, overexpression of AFAP1-AS1 was closely associated with lymph node metastasis (P < 0.001), distant metastasis (P = 0.016), advanced clinical stage (P = 0.002), and response to dCRT (P < 0.001). Kaplan-Meier survival analysis revealed that high expression of AFAP1-AS1 was significantly associated with shorter progression free survival (PFS) (median, 15 months vs. 27 months, P < 0.001) and overall survival (OS) (median, 29 months vs. 42 months, P < 0.001). In the multivariate analysis, high expression of AFAP1-AS1 was found to be an independent risk factor to predict poor PFS (HR, 1.626; P = 0.027) and OS (HR, 1.888; P = 0.004). Thus, high expression of AFAP1-AS1 could serve as a potential biomarker to predict tumor response and survival. Determination of this lncRNA expression might be useful for selection ESCC patients for dCRT. © 2016 The Authors. Molecular Carcinogenesis published by Wiley Periodicals, Inc.


Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Cisplatino/farmacología , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/genética , Esófago/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante/genética , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/radioterapia , Línea Celular Tumoral , Quimioradioterapia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas de Esófago , Esófago/patología , Esófago/efectos de la radiación , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Regulación hacia Arriba
9.
Onco Targets Ther ; 8: 3219-26, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26609239

RESUMEN

Long non-coding RNAs (lncRNAs), transcripts as longer than 200 nt in length with a great number of varieties in human genomics, play important roles in the regulation of genetics and epigenetics including gene transcription and post-transcription. Increasing evidence have demonstrated the upregulation of lncRNAs in tumorigenesis and metastasis of esophageal cancer (EC), a type of malignant tumors particularly in Asia. In this review, we briefly discuss the profiles and functions of lncRNAs involved in the progression of EC, which may provide a new approach to improve EC diagnosis and treatment.

10.
Yonsei Med J ; 56(6): 1497-502, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26446629

RESUMEN

PURPOSE: Heat shock proteins (HSPs) are highly conserved molecular chaperones. There are various studies that assess the prognostic value of HSPs in patients with esophageal cancer, but the conclusion remains controversial. This is the first meta-analysis study aiming to summarize the evidence on the suitability of HSPs to predict patients' survival. MATERIALS AND METHODS: Searching PubMed, Web of science and Medline until May 31, 2014, data were compared for overall survival in patients with down-regulated HSPs level with those with up-regulated level. We conducted a meta-analysis of 9 studies (801 patients) that correlated HSPs levels with overall survival. Data were synthesized with hazard ratios (HRs). RESULTS: The estimated risk of death was 2.93-fold greater in HSP27 negative patients than HSP27 positive patients [95% confidence interval (CI), 1.12-7.62]. When limited to esophageal squamous cell carcinoma (ESCC), the risk of death in HSP27 negative patients seemed more significant (HR, 3.90; 95% CI, 2.35-6.49). Decreased expression of HSP70 was also associated with worse survival in esophageal cancer (HR, 2.83; 95% CI, 1.90-4.23) and, when limited to ESCC, HR was 3.21 (95% CI, 1.94-5.30). Data collected, however, were not sufficient to determine the prognostic value of HSP90 in patients with ESCC nor esophageal adenocarcinomas (EADC). CONCLUSION: In this meta-analysis, reduced HSP27 and HSP70 expressions were associated with poor survival in patients with esophageal cancer, especially esophageal squamous cell carcinoma.


Asunto(s)
Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/metabolismo , Proteínas de Choque Térmico/metabolismo , Adenocarcinoma/mortalidad , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago , Regulación Neoplásica de la Expresión Génica , Proteínas de Choque Térmico HSP27 , Proteínas HSP70 de Choque Térmico , Proteínas HSP90 de Choque Térmico , Humanos , Masculino , Proteínas de Neoplasias , Pronóstico , Sobrevida , Resultado del Tratamiento
11.
Tumour Biol ; 36(4): 2501-7, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25731728

RESUMEN

Recent studies reveal that long noncoding RNAs (lncRNAs) play critical regulatory roles in cancer biology. Prostate cancer-associated ncRNA transcript 1 (PCAT-1) is one of the lncRNAs involved in cell apoptosis and proliferation of prostate cancer. This study aimed to assess the potential role of PCAT-1 specifically in the pathogenesis of esophageal squamous cell carcinoma (ESCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of PCAT-1 in matched cancerous tissues and adjacent noncancerous tissues from 130 patients with ESCC, 34 patients with non-small cell lung cancer (NSCLC), and 30 patients with gastric carcinoma (GC). The correlation of PCAT-1 with clinicopathological features and prognosis were also analyzed. The expression of PCAT-1 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (70.8%, p < 0.01), and the high level of PCAT-1 expression was significantly correlated with invasion of the tumor (p = 0.024), advanced clinical stage (p = 0.003), lymph node metastasis (p = 0.032), and poor prognosis. However, PCAT-1 mRNA expression had no significant difference between paired primary cancerous tissues and the adjacent noncancerous tissues in 34 cases of NSCLC (p = 0.293) and 30 cases of GC (p = 0.125). High expression of PCAT-1 was specifically correlated with invasion of cancer tissues, metastasis of lymph node, and advanced tumor stage of ESCC. High expression of PCAT-1 might reflect poor prognosis of ESCC and indicate a potential diagnostic target in ESCC patients. Adjuvant therapy targeting PCAT-1 molecule might be effective in treatment of ESCC.


Asunto(s)
Biomarcadores de Tumor/biosíntesis , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Pronóstico , ARN Largo no Codificante/biosíntesis , Adulto , Anciano , Apoptosis/genética , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/patología , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , ARN Largo no Codificante/genética
12.
Mol Cancer ; 14: 3, 2015 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-25608466

RESUMEN

BACKGROUND: Recent studies have demonstrated that long non-coding RNAs (lncRNAs) were present in the blood of cancer patients and have shown great potential as powerful and non-invasive tumor markers. However, little is known about the value of lncRNAs in the diagnosis of esophageal squamous cell carcinoma (ESCC). We hypothesized that ESCC-related lncRNAs might be released into the circulation during tumor initiation and could be utilized to detect and monitor ESCC. METHODS: Ten lncRNAs (HOTAIR, AFAP1-AS1, POU3F3, HNF1A-AS1, 91H, PlncRNA1, SPRY4-IT1, ENST00000435885.1, XLOC_013104 and ENST00000547963.1) which previously found to be differently expressed in esophageal cancer were selected as candidate targets for subsequent circulating lncRNA assay. A four-stage exploratory study was conducted to test the hypothesis: (1) optimization of detected method to accurately and reproducibly measure ESCC-related lncRNAs in plasma and serum; (2) evaluation of the stability of circulating lncRNAs in human plasma or serum; (3) exploration the origin of ESCC-related lncRNAs in vitro and in vivo; (4) evaluation the diagnostic power of circulating lncRNAs for ESCC. RESULTS: ESCC-related lncRNAs were detectable and stable in plasma of cancer patients, and derived largely from ESCC tumor cells. Furthermore, plasma levels of POU3F3, HNF1A-AS1 and SPRY4-IT1 were significantly higher in ESCC patients compared with normal controls. By receiver operating characteristic curve (ROC) analysis, among the three lncRNAs investigated, plasma POU3F3 provided the highest diagnostic performance for detection of ESCC (the area under the ROC curve (AUC), 0.842; p < 0.001; sensitivity, 72.8%; specificity, 89.4%). Moreover, use of POU3F3 and SCCA in combination could provide a more effective diagnosis performance (AUC, 0.926, p < 0.001, sensitivity, 85.7%; specificity, 81.4%). Most importantly, this combination was effective to detect ESCC at an early stage (80.8%). CONCLUSIONS: Plasma POU3F3 could serve as a potential biomarker for diagnosis of ESCC, and the combination of POU3F3 and SCCA was more efficient for ESCC detection, in particular for early tumor screening.


Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/diagnóstico , ARN Largo no Codificante/sangre , Animales , Antígenos de Neoplasias/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Estudios de Casos y Controles , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , Estadificación de Neoplasias , Estabilidad del ARN , Curva ROC , Reproducibilidad de los Resultados , Serpinas/metabolismo
13.
J Transl Med ; 12: 233, 2014 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-25169763

RESUMEN

BACKGROUND: Expression of the long non-coding RNA (lncRNA) LOC285194 was previously shown to be correlated with aggressive clinicopathological features and poor prognosis in several cancers. The aim of the present study was to explore the relationship between LOC285194 expression and clinical outcomes in esophageal squamous cell carcinoma (ESCC), so as to assess whether it could be a novel biomarker for prognosis and prediction of response to therapy on ESCC patients. METHODS: The method of quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure LOC285194 expression in pretreatment biopsy specimens and matched normal tissue derived from ESCC patients who underwent preoperative chemoradiotherapy followed by surgical resection (CRT + S group; n = 55) or from those who received surgical resection alone (S group; n = 87). The association between LOC285194 expression and clinicopathological features and prognosis were then analyzed. RESULTS: LOC285194 expression was significantly down-regulated in ESCC tumor tissues when compared with the adjacent normal tissues (p < 0.001). Low expression of LOC285194 was associated with larger tumor size (p = 0.002), advanced TNM stage (p = 0.018), more lymph node metastases (p = 0.013) and distant metastases (p = 0.015). In the CRT + S group, the pathological complete response rate was 57% (16/28) for the LOC285194-high group, and 15% (4/27) for the LOC285194-low group. Univariate analysis revealed that low expression of LOC285194 was significantly correlated with CRT response (p = 0.002). Moreover, Kaplan-Meier survival analysis revealed that patients with low expression of LOC285194 had a decreased disease free survival (DFS) (p < 0.001) and overall survival (OS) (p < 0.001). Multivariable analysis further identified low expression of LOC285194 as an independent prognosis factor for CRT response (p = 0.011), DFS (p < 0.001) and OS (p = 0.002). CONCLUSION: Decreased expression of LOC285194 could serve as a molecular marker to predict the clinical outcome of ESCC patients after surgery, and select patients who would benefit from preoperative CRT.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/terapia , Quimioradioterapia , Resistencia a Antineoplásicos/genética , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/terapia , ARN Largo no Codificante/genética , Tolerancia a Radiación/genética , Adulto , Anciano , Carcinoma de Células Escamosas/genética , Regulación hacia Abajo/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas de Esófago , Femenino , Regulación Neoplásica de la Expresión Génica , Estudios de Asociación Genética , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Resultado del Tratamiento , Células Tumorales Cultivadas
14.
Tumour Biol ; 35(8): 7743-54, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24810925

RESUMEN

LncRNA SPRY4-IT1 has been shown to promote the progression of melanoma. However, the role of lncRNA SPRY4-IT1 in human esophageal squamous cell carcinoma (ESCC) remains unclear. The purpose of this study is to investigate the clinical significance and biological functions of SPRY4-IT1 in ESCC. The expression levels of lncRNA SPRY4-IT in 92 ESCC patients and 8 ESCC cell lines were evaluated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The prognostic significance was evaluated using Kaplan-Meier and Cox regression analyses. Small interfering RNA (siRNA) was used to suppress SPRY4-IT1 expression in ESCC cell lines. Both in vitro and in vivo assays were performed to further explore its role in tumor progression. SPRY4-IT1 levels were significantly higher in ESCC tissues and cells than in corresponding adjacent noncancerous tissues and nontumorigenic esophageal epithelial cells, and the ESCC patients with higher SPRY4-IT1 expression had an advanced clinical stage and poorer prognosis than those with lower SPRY4-IT1 expression. The multivariate analysis revealed that SPRY4-IT1 expression level is an independent prognostic factor in ESCC patients. In vitro assays demonstrated that knockdown of SPRY4-IT1 reduced cell proliferation, invasiveness, and migration. In vivo assays demonstrated that knockdown of SPRY4-IT1 decreases cell growth. SPRY4-IT1 is a novel molecule involved in ESCC progression, which may provide a potential prognostic biomarker and a potential target for therapeutic intervention.


Asunto(s)
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas del Tejido Nervioso/genética , ARN Largo no Codificante/fisiología , Anciano , Animales , Carcinoma de Células Escamosas/mortalidad , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Esofágicas/mortalidad , Carcinoma de Células Escamosas de Esófago , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , ARN Largo no Codificante/genética , Regulación hacia Arriba
15.
Dig Dis Sci ; 59(3): 591-7, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24337686

RESUMEN

BACKGROUND: Recent studies revealed that long noncoding RNAs (lncRNAs) play critical regulatory roles in cancer biology. PlncRNA-1 is one of lncRNAs that is associated with cell apoptosis and proliferation of prostate cancer. AIM: This study aimed to assess the potential role of PlncRNA-1 in the pathogenesis of esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of PlncRNA-1 in 73 pairs of ESCC and their matched normal tissues. The correlation of PlncRNA-1 with clinicopathological features and clinical stages was also analyzed. Cancer cell proliferation and apoptosis were assessed following knock-down of PlncRNA-1 by MTT, colony formation assay, and flow cytometry. RESULTS: The expression of PlncRNA-1 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (69.8 %, p < 0.05), and the high level of PlncRNA-1 expression was significantly correlated with advanced clinical stage (p < 0.01) and lymph node metastasis (p < 0.05). Furthermore, knockdown of PlncRNA-1 reduced cell proliferation and increased the apoptosis in vitro. CONCLUSIONS: PlncRNA-1 plays an important role in ESCC cell proliferation. Overexpression of PlncRNA-1 is correlated with advanced tumor stage and lymph node metastasis, and may serve as a potential prognostic marker and therapeutic target for ESCC.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante/metabolismo , Regulación hacia Arriba , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Proliferación Celular , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Femenino , Citometría de Flujo , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
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