The Reprimo-Like Gene Is an Epigenetic-Mediated Tumor Suppressor and a Candidate Biomarker for the Non-Invasive Detection of Gastric Cancer.

Reprimo-like (RPRML) is an uncharacterized member of the Reprimo gene family. Here, we evaluated the role of RPRML and whether its regulation by DNA methylation is a potential non-invasive biomarker of gastric cancer. RPRML expression was evaluated by immunohistochemistry in 90 patients with gastric cancer and associated with clinicopathologic characteristics and outcomes. The role of RPRML in cancer biology was investigated in vitro, through RPRML ectopic overexpression. Functional experiments included colony formation, soft agar, MTS, and Ki67 immunofluorescence assays. DNA methylation-mediated silencing was evaluated by the 5-azacytidine assay and direct bisulfite sequencing. Non-invasive detection of circulating methylated RPRML DNA was assessed in 25 gastric cancer cases and 25 age- and sex-balanced cancer-free controls by the MethyLight assay. Downregulation of RPRML protein expression was associated with poor overall survival in advanced gastric cancer. RPRML overexpression significantly inhibited clonogenic capacity, anchorage-independent growth, and proliferation in vitro. Circulating methylated RPRML DNA distinguished patients with gastric cancer from controls with an area under the curve of 0.726. The in vitro overexpression results and the poor patient survival associated with lower RPRML levels suggest that RPRML plays a tumor-suppressive role in the stomach. Circulating methylated RPRML DNA may serve as a biomarker for the non-invasive detection of gastric cancer.

Tuberculosis vertebral con afectación pleural: reporte de un caso / Spinal tuberculosis with pleural involvement: a case report

Resumen La tuberculosis extrapulmonar representa hasta el 25% de todos los casos de tuberculosis. Los órganos más frecuentemente afectados son los ganglios linfáticos y la pleura. Alrededor del 10-11% de casos de tuberculosis extrapulmonar tienen afectación osteoarticular y de ellos la mitad con compromiso vertebral. La infección es causada por la diseminación hematógena del bacilo desde un foco primario al hueso esponjoso de los cuerpos vertebrales torácicos o lumbares principalmente. El síntoma característico es el dolor crónico de la columna vertebral, generalmente en el sitio afectado, sin otros síntomas o signos concomitantes. La asociación de tuberculosis vertebral con afectación pleural sin un foco pulmonar establecido es infrecuente, se ha descrito en 2.5% de pacientes e intriga acerca de su fisiopatología. En Colombia, no se encontraron reportes similares. Se describe el caso de una paciente joven con historia de dolor lumbar crónico que debutó con síntomas respiratorios persistentes asociado a síntomas constitucionales; en quien se comprobó la infección por Mycobacterium tuberculosis en vértebras toracolumbares y pleura. Este caso evidencia una historia natural atípica de la enfermedad, en la cual el mecanismo fisiopatológico parece haber sido la diseminación directa por contigüidad, y resalta la importancia de la sospecha clínica para garantizar un diagnóstico y tratamiento oportuno. MÉD.UIS.2020;33(3): 67-73

Abstract Extrapulmonary tuberculosis represents up to 25% of all cases of tuberculosis. The most frequently affected organs are lymph nodes, pleura and bone. Around 10-11% of cases of extrapulmonary tuberculosis have osteoarticular involvement and a half of them present vertebral involvement. The infection is caused by hematogenous spread of the bacillus from a primary focus to the cancellous bone of the thoracic or lumbar vertebral bodies mainly. The characteristic symptom is the chronic pain in the spine, usually in the affected site, without other concomitant symptoms or signs. The association between vertebral tuberculosis and pleural involvement without an established pulmonary focus is infrequent, it has been described in 2.5% of patients, an intrigue about its pathophysiology. Similar cases in Colombia have not been reported. This article describes a case of a young patient with a history of chronic low back pain that debuts with persistent respiratory symptoms associated with constitutional symptoms; whose Mycobacterium tuberculosis infection was proven in thoracolumbar vertebrae and pleura. This case shows an atypical natural history of the disease, in which the pathophysiological mechanism of the disease would seem to have been the direct dissemination by contiguity, and emphasizes the importance of clinical suspicion to ensure timely diagnosis and treatment. MÉD.UIS.2020;33(3): 67-73

The Reprimo Gene Family: A Novel Gene Lineage in Gastric Cancer with Tumor Suppressive Properties.

The reprimo (RPRM) gene family is a group of single exon genes present exclusively within the vertebrate lineage. Two out of three members of this family are present in humans: RPRM and RPRM-Like (RPRML). RPRM induces cell cycle arrest at G2/M in response to p53 expression. Loss-of-expression of RPRM is related to increased cell proliferation and growth in gastric cancer. This evidence suggests that RPRM has tumor suppressive properties. However, the molecular mechanisms and signaling partners by which RPRM exerts its functions remain unknown. Moreover, scarce studies have attempted to characterize RPRML, and its functionality is unclear. Herein, we highlight the role of the RPRM gene family in gastric carcinogenesis, as well as its potential applications in clinical settings. In addition, we summarize the current knowledge on the phylogeny and expression patterns of this family of genes in embryonic zebrafish and adult humans. Strikingly, in both species, RPRM is expressed primarily in the digestive tract, blood vessels and central nervous system, supporting the use of zebrafish for further functional characterization of RPRM. Finally, drawing on embryonic and adult expression patterns, we address the potential relevance of RPRM and RPRML in cancer. Active investigation or analytical research in the coming years should contribute to novel translational applications of this poorly understood gene family as potential biomarkers and development of novel cancer therapies.