Elementary screening of lymph node metastatic-related genes in gastric cancer based on the co-expression network of messenger RNA, microRNA and long non-coding RNA

Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. The high mortality might be attributed to delay in detection and is closely related to lymph node metastasis. Therefore, it is of great importance to explore the mechanism of lymph node metastasis and find strategies to block GC metastasis. Messenger RNA (mRNA), microRNA (miRNA) and long non-coding RNA (lncRNA) expression data and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. A total of 908 differentially expressed factors with variance >0.5 including 542 genes, 42 miRNA, and 324 lncRNA were screened using significant analysis microarray algorithm, and interaction networks were constructed using these differentially expressed factors. Furthermore, we conducted functional modules analysis in the network, and found that yellow and turquoise modules could separate samples efficiently. The groups classified in the yellow and turquoise modules had a significant difference in survival time, which was verified in another independent GC mRNA dataset (GSE62254). The results suggested that differentially expressed factors in the yellow and turquoise modules may participate in lymph node metastasis of GC and could be applied as potential biomarkers or therapeutic targets for GC.

Expression of hypoxia-inducible factor 1α is associated with lymph node metastasis in oral squamous cell carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To explore the association between hypoxia-inducible factor 1α (HIF-1α) expression and lymph node metastasis in oral squamous cell carcinoma (OSCC).@*METHODS@#Tumor specimens from 125 patients with histologically-proven, surgically-treated OSCC were examined by immunohistochemical staining for expression of HIF-1α. The patients were divided into two groups by the expression of HIF-1α, high expression of HIF -1α group (H-group) and low expression of HIF-1α group (L-group). The main assessment parameters were lymph node metastasis rate and disease-specific survival (DSS). The lymph node metastasis rate and clinicopathologic features were compared using Mann-Whitney test. The Kaplan-Meier curve was generated for each group and compared using the log-rank test. Cox proportional hazard models were utilized for multivariate analyses of HIF-1α expression and other baseline factors with DSS. All calculations and analyses were performed using the SPSS 17.0 software package.@*RESULTS@#The protein expression levels of HIF-1α were up-regulated in OSCC and two patients were unable to evaluate. There were 48 patients in L-group and 75 patients in H-group. Lymph node metastasis rate was 37.5% (18/48) for L-group and 58.7% (44/75) for H-group (P=0.027). Expression of HIF-1α was significantly correlated with lymph node metastasis. The patients of L-group had a significantly better DSS than the patients of H-group (70.8% vs. 46.7%, P=0.005), while the patients of L-group had a significantly better disease-free survival (DFS) than the patients of H-group (60.4% vs. 36.0%, P=0.009) by Kaplan-Meier method. A multivariate survival analysis also showed that HIF-1α expression (HR=2.164, 95%CI: 1.150-4.074, P=0.017) and T-stage (HR=1.387, 95%CI: 1.066-1.804, P=0.015) both were the independent factors associated with prognosis.@*CONCLUSION@#HIF-1α expression is significantly correlated with lymph node metastasis in OSCC. HIF-1α expression is an independent predictive factor for prognosis of OSCC patients, and may serve as a potential biomarker for molecular diagnosis and targeted therapy in future.

Papel del tecnólogo en medicina nuclear en el desarrollo de técnicas centellográficas, de cirugía radioguiada y moleculares / Nuclear medicine technologist role in the development of scintigraphy techniques of radioguided and molecular surgery

En nuestro centro el Tecnólogo en Medicina Nuclear interviene activamente en el desarrollo y evaluación de metodologías de Medicina Nuclear y de Biología Molecular vinculadas con la estrategia del ganglio centinela (GC). El objetivo del presente trabajo fue el de validar las técnicas nucleares y moleculares utilizadas mediante parámetros clínicos y pronósticos conocidos de la enfermedad. Incluimos prospectivamente 40 pacientes con melanoma clínicamente localizado, con un espesor medio de Breslow de 3.6 mm (rango: 0.5-15.0 mm). La edad media de los pacientes fue de 54.2 años (rango: 24-82 años), siendo 25 del sexo femenino. Se utilizó como radiofármaco al 99mTc – nanocoloide de albúmina, realizando el estudio linfocentellográfico 16-18 horas antes de la cirugía, con una dosis total de 111-185 MBq. Se adquirieron imágenes secuenciales de 5 minutos en gama cámara, continuando hasta una hora post inyección de no visualizarse precozmente drenaje. Una vez localizado el(los) GC, realizamos vistas ortogonales a los efectos de localizar dichos ganglios en el espacio tridimensional. Los territorios ganglionares identificados mediante linfocentellografía fueron explorados quirúrgicamente mediante la ayuda de una sonda gama intraoperatoria. La radiactividad ganglionar y de los tejidos adyacentes fue medida in vivo y verificada ex vivo luego de la resección. Una relación de conteo ganglio/fondo mayor a 2 in vivo y mayor a 10 veces ex vivo fue considerada a los efectos de considerar un ganglio como GC. Los mismos fueron analizados mediante histopatología y en 14 pacientes se estudió además la expresión mediante RT-PCR, de los marcadores TIR, MART-1 y MIA, usando un protocolo de una fase con 35 ciclos de amplificación. Los experimentos fueron realizados en duplicado e incluyeron controles positivos y negativos. Los GC fueron identificados en 38/39 pacientes operables (97.4 por ciento), extirpándose una media de 1.3 ganglios. Se diagnosticaron metástasis ganglionares por his.

Genetic Alterations in Primary Gastric Carcinomas Correlated with Clinicopathological Variables by Array Comparative Genomic Hybridization

Genetic alterations have been recognized as an important event in the carcinogenesis of gastric cancer (GC). We conducted high resolution bacterial artificial chromosome array-comparative genomic hybridization, to elucidate in more detail the genomic alterations, and to establish a pattern of DNA copy number changes with distinct clinical variables in GC. Our results showed some correlations between novel amplified or deleted regions and clinical status. Copy-number gains were frequently detected at 1p, 5p, 7q, 8q, 11p, 16p, 20p and 20q, and losses at 1p, 2q, 4q, 5q, 7q, 9p, 14q, and 18q. Losses at 4q23, 9p23, 14q31.1, or 18q21.1 as well as a gain at 20q12 were correlated with tumor-node-metastasis tumor stage. Losses at 9p23 or 14q31.1 were associated with lymph node status. Metastasis was determined to be related to losses at 4q23 or 4q28.2, as well as losses at 4q15.2, 4q21.21, 4q 28.2, or 14q31.1, with differentiation. One of the notable aspects of this study was that the losses at 4q or 14q could be employed in the evaluation of the metastatic status of GC. Our results should provide a potential resource for the molecular cytogenetic events in GC, and should also provide clues in the hunt for genes associated with GC.

Association of DNA pattern of metastatic lymph node with disease free survival in patients with intraoral squamous cell carcinoma.

BACKGROUND AND OBJECTIVE: Intraoral squamous cell carcinoma (OSCC) is one of the common tobacco related cancers affecting Indian population. These tumours are slow growing, endophytic and are mostly well differentiated. Cervical lymph node is the common site of metastasis of these tumours. In most of the patients cervical lymph node metastasis rather than the primary tumour, affects prognosis. However, no reports are available on the DNA pattern of the metastatic lymph nodes in patients with intraoral squamous cell carcinoma. Therefore, the present study was undertaken to observe DNA pattern of primary tumours and their corresponding metastatic lymph nodes and its association with the clinicopathological parameters and prognosis. METHODS: DNA flow cytometry was successfully carried out on 68 paraffin embedded specimens of the primary tumours and their 22 corresponding metastatic cervical lymph nodes. The findings were evaluated for their possible association with clinicopathological features of the tumour and disease free survival of patients with intraoral carcinoma. RESULTS: Analysis of nuclear DNA patterns revealed 32 (47.0%) diploidy and 36 (52.9%) aneuploidy in primary tumours whereas metastatic lymph nodes showed 7 (31.8%) diploidy and 15 (68.1%) aneuploidy. The aneuploidy group in metastatic lymph node had significantly higher S phase fraction (SPF) (P<0.01) and poor histological grade (P<0.002) as compared to their counterparts with diploidy. DNA pattern of metastatic lymph node further showed a significant association with disease free survival in the log rank test. Aneuploidy and high SPF in metastatic lymph node was found to be associated with early recurrence while DNA pattern of the primary tumour did not show significant association with the disease free survival. INTERPRETATION AND CONCLUSION: It may be concluded that aneuploidy and high SPF in metastatic lymph node might be considered as an important discriminatory risk factor in patients with similarly staged intraoral squamous cell carcinoma.

Influencia del genotipo del huesped en la formacion de las metastasis de un linfoma transplantable de rata / Influence of host genotype in the development of metastasis in a transplantable lymphoma in rats

Se estudió el comportamiento de un linfoma transplantable de rata (L-TACB) en tres líneas m, e R y e S con diferente susceptibilidad al tumor y a la frecuencia de metástasis, y en los híbridos mx eR, mx eS y eRx eS. Los tumores de la línea m tuvieron mayor tamño (p < 0,01) que los de eR. Sin embargo, el porcentaje de regresión fue menor (p < 0.001) en eR, evidenciando que la tasa de crecimiento del L-TACB fue independiente de la capacidad de rechazo del tumor. En la línea m y en el híbrido mx eS, apesar de desarrollar tumores muy grandes, sólo un animal de cada grupo tuvo metástasis; en cambio, en la sublínea eR en el híbrido mx eR con tumores de tamaños similares o menortes, la frecuencia de metástasis fue mucho mayor (p < 0,01). La aparición de metástasis estuvo parcialmente asociada al tamaño tumral. Estos resultado sugieren que el crescimiento del L-TACB, la capacidad de rechazo y la formación de metástasis estarían regidos por genes independientes con cierto grado de asociación