Clinical and pathological characteristics associated with the presence of the IS6110 Mycobacterim tuberculosis transposon in neoplastic cells from non-small cell lung cancer patients

非小细胞肺癌患者肿瘤细胞中 IS6110 结核分枝杆菌转座子存在相关的临床和病理特征

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作者:Oscar Arrieta, Camilo Molina-Romero, Fernanda Cornejo-Granados, Brenda Marquina-Castillo, Alejandro Avilés-Salas, Gamaliel López-Leal, Andrés F Cardona, Alette Ortega-Gómez, Mario Orozco-Morales, Adrián Ochoa-Leyva, Rogelio Hernandez-Pando0

Abstract

Lung cancer (LC) and pulmonary tuberculosis (TB) are the deadliest neoplastic and bacterial infectious diseases worldwide, respectively. Clinicians and pathologists have long discussed the co-existence of LC and TB, and several epidemiologic studies have presented evidence indicating that TB could be associated with the development of LC, particularly adenocarcinoma. Nonetheless, this data remains controversial, and the mechanism which could underlie the association remains largely unexplored. Some bioinformatic studies have shown that human cancer biopsies have a very high frequency of bacterial DNA integration; since Mycobacterium Tuberculosis (MTb) is an intracellular pathogen, it could play an active role in the cellular transformation. Our group performed an exploratory study in a cohort of 88 LC patients treated at the Instituto Nacional de Cancelorogía (INCan) of Mexico City to evaluate the presence of MTb DNA in LC tissue specimens. For the first time, our results show the presence of the MTb IS6110 transposon in 40.9% (n = 36/88) of patients with lung adenocarcinomas. Additionally, through in-situ PCR we identified the presence of IS6110 in the nuclei of tumor cells. Furthermore, shotgun sequencing from two samples identified traces of MTb genomes present in tumor tissue, suggesting that similar Mtb strains could be infecting both patients.

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