RESUMEN
Microsatellite instability (MSI) assessment is strongly recommended for colorectal cancer patients, as MSI status is crucial in determining optimal treatment and predicting prognosis. This study evaluated the reliability and accuracy of a novel polymerase chain reaction (PCR)-based 8-loci MSI test kit, a rapid test kit designed to detect MSI, by comparing its performance with immunohistochemistry (IHC) and the National Cancer Institute (NCI) 2B3D Panel. MSI status was determined in 186 formalin-fixed paraffin-embedded (FFPE) colorectal cancer tissue samples with known mismatch repair (MMR) status by IHC using the novel PCR-based 8-loci MSI test kit. Additionally, the consistency between the NCI 2B3D Panel and the novel PCR-based 8-loci panel was compared using 69 FFPE tumor tissues paired with adjacent non-cancerous tissue. The novel PCR-based 8-loci MSI test kit and IHC demonstrated high concordance (overall agreement: 97.8%). However, four samples displayed discordant results, exhibiting MMR deficiency using IHC and microsatellite stability using the novel PCR-based 8-loci MSI test kit. Of the 69 samples reanalyzed using the NCI 2B3D Panel, high concordance with the novel PCR-based 8-loci MSI test kit was observed in 67 of 69 cases (overall agreement: 97.1%). The novel PCR-based 8-loci MSI test kit is a rapid and reliable tool for accurately detecting MSI status in colorectal cancer.
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Neoplasias Colorrectales , Inestabilidad de Microsatélites , Reacción en Cadena de la Polimerasa , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Juego de Reactivos para Diagnóstico , Femenino , Masculino , Persona de Mediana EdadRESUMEN
Colorectal cancer (CRC) is a common malignancy of the gastrointestinal tract. CircRNAs have been reported to play regulatory roles in many cancers, including CRC. This study focuses on the role of circ_0007331 in CRC. Differentially expressed circRNAs in CRC were screened using the GEO database. RT-qPCR was used to analyze mRNA expression. StarBase and TargetScan were used to predict targeting relationships and then verified by the dual luciferase reporter assay along with the RNA pull-down assay. CCK-8 as well and transwell assays were used to measure cell viability, migration, and invasion. Protein levels were determined using western blotting. circ_0007331 is expressed more frequently in patients with CRC. The inhibition of circ_0007331 expression reduced the viability, colony formation, migration, and invasion of CRC cells. However, inhibition of miR-205-5p or elevation of high-mobility group A2 (HMGA2) can reverse the function of inhibited circ_0007331 in tumor cells. This study demonstrated that the circ_0007331/miR-205-5p/HMGA2 axis promotes CRC development. Thus, circ_0007331 may be a potential biomarker for CRC.
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Neoplasias Colorrectales , MicroARNs , Proliferación Celular/genética , Neoplasias Colorrectales/metabolismo , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genéticaRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Currently, there is limited knowledge of dysregulation of cellular proliferation and apoptosis that contribute to the malignant phenotype in HCC. Copper metabolism gene MURR1 domain 10 (COMMD10) is initially identified as a suppressor gene in the pathogenesis of HCC in our observations. Here we aimed to explore its function and prognostic value in the progression of HCC. METHODS: Functional experiments were performed to explore the role of COMMD10 in HCC. The molecular mechanisms of COMMD10 were determined by luciferase assay, immunofluorescence, and immunoprecipitation. The nomogram was based on a retrospective and multicenter study of 516 patients who were pathologically diagnosed with HCC from three Chinese hospitals. The predictive accuracy and discriminative ability of the nomogram were determined by a C-index and calibration curve and were compared with COMMD10 and the Barcelona Clinic Liver Cancer (BCLC) staging system. The primary endpoint was overall survival (OS). RESULTS: COMMD10 expression was significantly lower in HCC than that in normal liver tissues. In vitro and in vivo experiments revealed that COMMD10 suppressed cell proliferation and induced apoptosis in HCC. Mechanistically, COMMD10 inhibits TNFα mediated ubiquitination of IκBα and p65 nuclear translocation through the combination of COMMD10-N terminal to the Rel homology domain of p65, which inhibited NF-κB activity and increased expression of cleaved caspase9/3 in HCC. Clinically, COMMD10 stratifies early-stage HCC patients into two risk groups with significantly different OS. Additionally, the nomogram based on COMMD10 and BCLC stage yielded more accuracy than BCLC stage alone for predicting OS of HCC patients in three cohorts. CONCLUSIONS: COMMD10 suppresses proliferation and promotes apoptosis by inhibiting NF-κB signaling and values up BCLC staging in predicting OS, which provides evidence for the identification of potential therapeutic targets and the accurate prediction of prognosis for patients with HCC.
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Carcinoma Hepatocelular/patología , Péptidos y Proteínas de Señalización Intracelular/fisiología , Neoplasias Hepáticas/patología , FN-kappa B/antagonistas & inhibidores , Transducción de Señal/fisiología , Apoptosis/fisiología , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Proliferación Celular/fisiología , Progresión de la Enfermedad , Humanos , Neoplasias Hepáticas/metabolismo , FN-kappa B/metabolismo , Pronóstico , Unión Proteica , Estudios Retrospectivos , Análisis de Supervivencia , Factor de Necrosis Tumoral alfa/metabolismo , UbiquitinaciónRESUMEN
This study aimed to evaluate correlations between lymphovascular invasion (LVI) and the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2), Ki-67, CK5/6, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), E-cadherin, BCL11A and P53 in invasive breast cancer and to identify predictors of LVI based on these pathological factors. In all, 392 paraffin-embedded tissues from consecutive patients with primary operable invasive breast cancer were included. Immunohistochemistry (IHC) was retrospectively performed using a tissue microarray (TMA) of the paraffin-embedded tissues. LVI-positive rates were compared using the χ2 test. Correlations between pathological factors were assessed using Spearman's test. Binary logistic regression was employed in multivariate analyses of statistically significant factors. The results showed that LVI positivity was significantly higher in patients with HER-2-positive expression or high Ki-67 expression. HER-2 expression was weakly positively correlated with Ki-67 expression. HER-2-positive expression and high Ki-67 expression were found to be risk factors for LVI, and associations between LVI and other pathological factors were not significant. Therefore, HER-2-positive expression and high Ki-67 expression are predictors of LVI, whereas the expression of ER, PR, CK5/6, EGFR, VEGF, E-cadherin, BCL11A and P53 is not associated with LVI in invasive breast cancer.
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The aim of this study was to evaluate the correlation between lymphovascular invasion (LVI) and tumor size, histological grade, and the expression statuses of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2), Ki67, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), E-cadherin, and P53 in invasive breast cancer, then establish a prediction model of LVI based on the associated clinicopathological factors.A total of 392 patients with primary invasive breast cancers were enrolled, and their paraffin-embedded tissues were manufactured into the tissue microarray. We evaluated the expression statuses of ER, PR, HER-2, Ki67, EGFR, VEGF, E-cadherin, and P53 based on immunohistochemistry, histological grade and LVI based on the hematoxylin and eosin stain, and tumor size.The positivity of LVI was significantly higher in the patients with HER-2 positive expression, Ki67 high expression, and tumor size >2âcm by Chi-square test. HER-2, Ki67, and tumor size were risk factors of LVI by multivariate analysis. The areas under the receiver operating curve of HER-2, Ki67, tumor size, and the combination of the 3 clinicopathological factors were 0.614 [Pâ=â.001, 95% confidence interval (CI): 0.544-0.683], 0.596 (Pâ=â.006, 95% CI: 0.529-0.662), 0.575 (Pâ=â.03, 95% CI: 0.510-0.641), and 0.670 (Pâ<â.001, 95% CI: 0.607-0.734), respectively.HER-2 positive expression, Ki67 high expression, and tumor size >2âcm were risk factors of LVI, whereas the power of the prediction model of LVI based on the 3 clinicopathological factors in invasive breast cancer was low.
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Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Metástasis Linfática/diagnóstico , Modelos Biológicos , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Femenino , Humanos , Inmunohistoquímica , Antígeno Ki-67/metabolismo , Modelos Logísticos , Persona de Mediana Edad , Análisis Multivariante , Clasificación del Tumor , Curva ROC , Receptor ErbB-2/metabolismo , Factores de Riesgo , Carga Tumoral , Adulto JovenRESUMEN
Nasopharyngeal carcinoma (NPC) is an EBV-associated malignant tumor of nasopharynx. As extremely rare condition, the second primary cancer of nasopharynx can occur in NPC patients synchronously or subsequently. Extramedullary plasmacytoma (EMP) is a rare tumor and commonly originates in the head and neck region. However, there is no report to describe a collision tumor of NPC and EMP occurring in the same nasopharyngeal mass. We report here an unusual case of synchronous coexistence of NPC and EMP occurring in the nasopharynx of an old male patient. A 63-year-old male patient presented with a 3-month history of right-sided nasal obstruction and recently intermittent epistaxis without enlargement of cervical lymph nodes. The solitary mass of nasopharynx was found by radiological and nasopharyngeal examination. Histologically, the mass contained two separated portions and displayed typically histological features of NPC and EMP, respectively. In EMP portion, the tumor was composed of monomorphic plasmacytoid-appearing cells with immuno-positive to CD79a, CD138, CD38, MUM-1 and CD56, but lack immunoreactivity to pan-CK (AE1/AE3), CD20, CD21 and EBERs. In NPC portion, the tumor cells formed irregular-shaped islands with diffusely immuno-positive to pan-CK (AE1/AE3), EMA and EBERs, but lack expressions of lymphoplasmacytic markers. A diagnosis of simultaneous occurrence of EMP and NPC in nasopharynx was made. There was no evidence of tumor recurrence or metastasis 18-month follow-up after radiotherapy. To our knowledge, it may be the first case of coexistence of EMP and NPC synchronously. In addition, the histological differential diagnosis and relevant potential mechanism of this unusual collision tumor were also discussed.
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Neoplasias Nasofaríngeas/patología , Neoplasias Primarias Múltiples/patología , Plasmacitoma/patología , Biomarcadores de Tumor/análisis , Carcinoma , Endoscopía , Epistaxis/etiología , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Inmunohistoquímica , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/química , Neoplasias Nasofaríngeas/complicaciones , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/virología , Neoplasias Primarias Múltiples/química , Neoplasias Primarias Múltiples/complicaciones , Neoplasias Primarias Múltiples/terapia , Neoplasias Primarias Múltiples/virología , Plasmacitoma/química , Plasmacitoma/complicaciones , Plasmacitoma/terapia , Plasmacitoma/virología , Resultado del TratamientoRESUMEN
OBJECTIVE: To establish transplanted models of VX2 tongue carcinoma in rabbits by three methods and compare these models. METHODS: After establishment of VX2 tumor-bearing rabbits, 72 New-Zealand white rabbits were randomly divided into 3 groups. Intact tumour tissue, modified tumour cell suspension, tumour cell suspension were respectively injected into the middle-third lateral border of the tongues of rabbits in 3 groups to induce transplanted VX2 tongue carcinoma. The histological features, the tumour-take rates and the metastasis rates of the 3 models were observed. RESULTS: The tumour-take rate of 3 models were 83.3%, 91.7% and 33.3% respectively; the lymph node metastasis rates were 71.4%, 100.0% and 37.5% respectively; the lung metastasis rates were 35.7%, 81.3% and 0 respectively. The histological features of the transplanted VX2 tongue carcinoma of 3 models were all consistent with those of moderately differentiated carcinoma. CONCLUSION: The biological properties of the transplanted VX2 tongue carcinoma of 3 models is much alike to tongue carcinoma in humans. The model established with modified tumor cell suspension is considered to be more suitable for tongue cancer study.