Effects of THBS3, SPARC and SPP1 expression on biological behavior and survival in patients with osteosarcoma

BACKGROUND: Osteosarcoma is a very aggressive tumor with a propensity to metastasize and invade surrounding tissue. Identification of the molecular determinants of invasion and metastatic potential may guide the development of a rational strategy for devising specific therapies that target the pathways leading to osteosarcoma. METHODS: In this study, we used pathway-focused low density expression cDNA arrays to screen for candidate genes related to tumor progression. Expression patterns of the selected genes were validated by real time PCR on osteosarcoma patient tumor samples and correlated with clinical and pathological data. RESULTS: THBS3, SPARC and SPP1 were identified as genes differentially expressed in osteosarcoma. In particular, THBS3 was expressed at significantly high levels (p = 0.0001) in biopsies from patients with metastasis at diagnosis, which is a predictor of worse overall survival, event-free survival and relapse free survival at diagnosis. After chemotherapy, patients with tumors over-expressing THBS3 have worse relapse free survival. High SPARC expression was found in 51/55 (96.3%) osteosarcoma samples derived from 43 patients, and correlated with the worst event-free survival (p = 0.03) and relapse free survival (p = 0.07). Overexpression of SPP1 was found in 47 of 53 (89%) osteosarcomas correlating with better overall survival, event-free survival and relapse free survival at diagnosis. CONCLUSION: In this study three genes were identified with pattern of differential gene expression associated with a phenotypic role in metastasis and invasion. Interestingly all encode for proteins involved in extracellular remodeling suggesting potential roles in osteosarcoma progression. This is the first report on the THBS3 gene working as a stimulator of tumor progression. Higher levels of THBS3 maintain the capacity of angiogenesis. High levels of SPARC are not required for tumor progression but are necessary for tumor growth and maintenance. SPP1 is not necessary for tumor progression in osteosarcoma and may be associated with inflammatory response and bone remodeling, functioning as a good biomarker

Cultivation-Independent Methods Reveal Differences among Bacterial Gut Microbiota in Triatomine Vectors of Chagas Disease

Chagas disease is one of the most important endemic diseases of South and Central America. Its causative agent is the protozoan Trypanosoma cruzi, which is transmitted to humans by blood-feeding insects known as triatomine bugs. These vectors mainly belong to Rhodnius, Triatoma and Panstrongylus genera of Reduviidae. The bacterial communities in the guts of these vectors may have important effects on the biology of T. cruzi. For this reason, we analyzed the bacterial diversity hosted in the gut of different species of triatomines using cultivation-independent methods. Among Rhodnius sp., we observed similar bacterial communities from specimens obtained from insectaries or sylvatic conditions. Endosymbionts of the Arsenophonus genus were preferentially associated with insects of the Panstrongylus and Triatoma genera, whereas the bacterial genus Serratia and Candidatus Rohrkolberia were typical of Rhodnius and Dipetalogaster, respectively. The diversity of the microbiota tended to be the largest in the Triatoma genus, with species of both Arsenophonus and Serratia being detected in T. infestans