Functional and genomic characterization of three novel cell lines derived from a metastatic gallbladder cancer tumor

BACKGROUND: Gallbladder cancer (GBC) is the most common tumor of the biliary tract. The incidence of GBC shows a large geographic variability, being particularly frequent in Native American populations. In Chile, GBC represents the second cause of cancer-related death among women. We describe here the establishment of three novel cell lines derived from the ascitic fluid of a Chilean GBC patient, who presented 46% European, 36% Mapuche, 12% Aymara and 6% African ancestry. RESULTS: After immunocytochemical staining of the primary cell culture, we isolated and comprehensively characterized three independent clones (PUC-GBC1, PUC-GBC2 and PUC-GBC3) by short tandem repeat DNA profiling and RNA sequencing as well as karyotype, doubling time, chemosensitivity, in vitro migration capability and in vivo tumorigenicity assay. Primary culture cells showed high expression of CK7, CK19, CA 19-9, MUC1 and MUC16, and negative expression of mesothelial markers. The three isolated clones displayed an epithelial phenotype and an abnormal structure and number of chromosomes. RNA sequencing confirmed the increased expression of cytokeratin and mucin genes, and also of TP53 and ERBB2 with some differences among the three cells lines, and revealed a novel exonic mutation in NF1. The PUC-GBC3 clone was the most aggressive according to histopathological features and the tumorigenic capacity in NSG mice. CONCLUSIONS: The first cell lines established from a Chilean GBC patient represent a new model for studying GBC in patients of Native American descent.

Estilo de vida y agresividad del cáncer de próstata / Lifestyle and aggressiveness of prostate cancer

El objetivo de este estudio fue establecer una asociación entre diversas variables demográficas y epidemiológicas con la agresividad del cáncer de próstata (CaP). Métodos: pacientes diagnosticados con CaP respondieron una encuesta que incluye el nivel de educación, los factores de riesgo cardiovascular (FRCV), los antecedentes familiares (HF) de CaP, consumo de alcohol, tabaquismo y otros. Se utilizó análisis univariado y multivariado (AMV) para establecer si los factores mencionados anteriormente afectan las variables asociadas con la agresividad del CaP, como la edad al momento del diagnóstico, el índice de Gleason, los márgenes positivos (MP) y las metástasis óseas (MO), entre otras. Resultados: se incluyeron ciento setenta y dos hombres en el análisis. Los pacientes con HF fueron diagnosticados a edades más tempranas que los pacientes sin HF (55,73 vs 66,45 años, p = 0,0001). Los pacientes que beben tienen un mayor número de MP que los pacientes que no (15 vs 4 pacientes, p = 0,04). El AMV mostró que los pacientes que consumen alcohol y los que fuman (activos o suspendidos) tuvieron un mayor riesgo de MP (OR = 4,45 y 4,1, IC 95 por ciento 1,16-17,07 y 1,14-14,72, respectivamente, ambos p <0,05). Los pacientes con mayor nivel de educación presentaron un mayor riesgo de CaP confinado (OR = 3,42, IC 95 por ciento 1,392-8,434, p = 0,007). Conclusiones: los pacientes que consumen alcohol, fuman y tienen un menor nivel de educación presentaron un mayor riesgo de desarrollar CaP agresivo. (AU)

The aim of this study was to establish an association between various demographic and epidemiological variables with aggressiveness of prostate cancer (PCa). Methods: Patients diagnosed with PCa, answered a survey that include level of education, cardiovascular risk factors (CVRF), family history (FH) of PCa, alcohol intake, smoke and others. Univariate and multivariate analysis (MVA) were used to establish whether the factors mentioned above affect variables associated with aggressiveness of PCa such as: age at diagnosis, Gleason score, positive margins (PM), and bone metastasis (BM). Results: One hundred and seventy two men were included in the analysis. Patients with FH had cancer diagnosed at younger ages (55.73 years to FH vs 66.45 years to no FH, p = 0.0001). Patients who drink had higher number of PM than patients who did not (15 vs 4 patients, p= 0.04). MVA showed that patients who consumed alcohol and patients who smoked (active or suspended) had an increased risk of PM (OR= 4.45 and 4.1, 95 percent CI 1.16-17.07 and 1.14-14.72, respectively, both p<0.05). Patients with higher level of education presented an increased risk of confined PCa (OR= 3.42, 95 percent CI 1.392-8.434, p= 0.007). Conclusions: Patients who consume alcohol, smoke and have lower level of education presented a higher risk of developing aggressive PCa. (AU)