Gene Expression Clustering and Selected Head and Neck Cancer Gene Signatures Highlight Risk Probability Differences in Oral Premalignant Lesions

BACKGROUND: Oral premalignant lesions (OPLs) represent the most common oral precancerous conditions. One of the major challenges in this field is the identification of OPLs at higher risk for oral squamous cell cancer (OSCC) development, by discovering molecular pathways deregulated in the early steps of malignant transformation. Analysis of deregulated levels of single genes and pathways has been successfully applied to head and neck squamous cell cancers (HNSCC) and OSCC with prognostic/predictive implications. Exploiting the availability of gene expression profile and clinical follow-up information of a well-characterized cohort of OPL patients, we aim to dissect tissue OPL gene expression to identify molecular clusters/signatures associated with oral cancer free survival (OCFS). MATERIALS AND METHODS: The gene expression data of 86 OPL patients were challenged with: an HNSCC specific 6 molecular subtypes model (Immune related: HPV related, Defense Response and Immunoreactive; Mesenchymal, Hypoxia and Classical); one OSCC-specific signature (13 genes); two metabolism-related signatures (3 genes and signatures raised from 6 metabolic pathways associated with prognosis in HNSCC and OSCC, respectively); a hypoxia gene signature. The molecular stratification and high versus low expression of the signatures were correlated with OCFS by Kaplan-Meier analyses. The association of gene expression profiles among the tested biological models and clinical covariates was tested through variance partition analysis. RESULTS: Patients with Mesenchymal, Hypoxia and Classical clusters showed an higher risk of malignant transformation in comparison with immune-related ones (log-rank test, p = 0.0052) and they expressed four enriched hallmarks: "TGF beta signaling" "angiogenesis", "unfolded protein response", "apical junction". Overall, 54 cases entered in the immune related clusters, while the remaining 32 cases belonged to the other clusters. No other signatures showed association with OCFS. Our variance partition analysis proved that clinical and molecular features are able to explain only 21% of gene expression data variability, while the remaining 79% refers to residuals independent of known parameters. CONCLUSIONS: Applying the existing signatures derived from HNSCC to OPL, we identified only a protective effect for immune-related signatures. Other gene expression profiles derived from overt cancers were not able to identify the risk of malignant transformation, possibly because they are linked to later stages of cancer progression. The availability of a new well-characterized set of OPL patients and further research is needed to improve

Pueblos indígenas, estados nacionales y fronteras : tensiones y paradojas de los procesos de transición contemporáneos en América Latina. Tomo II

Si hay un rasgo inherente a América Latina en las últimas décadas que permite caracterizarla en muy pocas palabras, son sus grandes y aceleradas transformaciones. Dentro de estos cambios, los pueblos indígenas ocupan un lugar sumamente protagónico, lo cual resulta sorprendente si lo comparamos con la situación de algunas décadas atrás. Es más sorprendente aún, si lo contrastamos con lo que imaginaban los ideólogos de los genocidios perpetrados en tantos lugares de la región en la época de la conformación de los Estados nacionales. Sin duda la situación de los pueblos indígenas en la región es un tema de tal complejidad, multidimensionalidad y al mismo tiempo dinamismo, que cualquier recorte temático, temporal y espacial que se efectúe de la cuestión indígena despierta una sinfín de interrogantes, sobre los cuales es menester profundizar. El propósito central de esta compilación es abordar la situación histórica y actual de los pueblos indígenas de América Latina, considerando las profundas transformaciones socioeconómicas, políticas y culturales que se vienen registrando en función de los procesos de transición contemporáneos