Integrative multi-omics analysis identifies a prognostic miRNA signature and a targetable miR-21-3p/TSC2/ mTOR axis in metastatic pheochromocytoma/ paraganglioma

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar y los autores pertenecientes a la UAMPheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that present variable outcomes. To date, no effective therapies or reliable prognostic markers are available for patients who develop metastatic PPGL (mPPGL). Our aim was to discover robust prognostic markers validated through in vitro models, and define specific therapeutic options according to tumor genomic features. Methods: We analyzed three PPGL miRNome datasets (n=443), validated candidate markers and assessed them in serum samples (n=36) to find a metastatic miRNA signature. An integrative study of miRNome, transcriptome and proteome was performed to find miRNA targets, which were further characterized in vitro. Results: A signature of six miRNAs (miR-21-3p, miR-183-5p, miR-182-5p, miR-96-5p, miR-551b-3p, and miR-202-5p) was associated with metastatic risk and time to progression. A higher expression of five of these miRNAs was also detected in PPGL patients’ liquid biopsies compared with controls. The combined expression of miR-21-3p/miR-183-5p showed the best power to predict metastasis (AUC=0.804, P=4.67·10-18), and was found associated in vitro with pro-metastatic features, such as neuroendocrine-mesenchymal transition phenotype, and increased cell migration rate. A pan-cancer multi-omic integrative study correlated miR-21-3p levels with TSC2 expression, mTOR pathway activation, and a predictive signature for mTOR inhibitor-sensitivity in PPGLs and other cancers. Likewise, we demonstrated in vitro a TSC2 repression and an enhanced rapamycin sensitivity upon miR-21-3p expression. Conclusions: Our findings support the assessment of miR-21-3p/miR-183-5p, in tumors and liquid biopsies, as biomarkers for risk stratification to improve the PPGL patients’ management. We propose miR-21-3p to select mPPGL patients who may benefit from mTOR inhibitorsThis work was supported by the Instituto de Salud Carlos III (ISCIII), Acción Estratégica en Salud, cofounded by FEDER, [grant number PI14/00240, PI17/01796 to M.R., PI15/00783 to A.C], the Paradifference Foundation [no grant number applicable to M.R.], the ANR [ANR-2011-JCJC-00701 MODEOMAPP to AP.G-R], the European Union [FP7/2007-2013 n° 259735, Horizon 2020 n° 633983 to AP.G-R], Epigénétique et Cancer [EPIG201303 METABEPIC to AP.G-R], the the Ligue Nationale contre le Cancer ["Cartes d'Identité des Tumeurs (CIT) program" to AP.G-R], the Institut National du Cancer, the Direction Générale de l’Offre de Soins [PRT-K 2014, COMETE-TACTIC, INCa-DGOS_8663 to AP.G-R], the Deutsche Forschungsgemeinschaft (DFG) [CRC/Transregio 205/1 “The Adrenal: Central Relay in Health and Disease“ to F.B, M.F and G.E], the Rafael del Pino Foundation [Becas de Excelencia Rafael del Pino 2017 to B.C], the Severo Ochoa Excellence Programme [project SEV-2011-0191 to M.C-F], La Caixa Foundation [B004235 to JM.R-R], the Spanish Ministry of Education, Culture and Sport [grant number FPU16/05527 to M.S.], the Site de Recherche Intégré sur le Cancer-SIRIC [CARPEM Project to N.B.] and the AECC Foundation [grant number AIO15152858 to C.M-C

Motherhood in Spain : From the "Baby Boom" to "Structural Infertility"

We analyze the mechanisms of reproductive governance that influence reproduction in Spain through 66 semi-structured interviews with heterosexual parents. We examine reproductive governance through moral regimes surrounding four arenas: the labor market, gender relations at home, institutional feminist discourses, and the narrative of choice. We show that mothers are considered to be socially responsible for children, a fact that is key to understanding how Spain went from a "baby boom" between the 1950 and 1970s to "structural infertility" since the 1990s.Esta investigación aborda la gobernanza reproductiva en España a través de cuatro dimensiones de regímenes morales: el mercado laboral, las relaciones de género, el discurso del feminismo institucional y las narrativas de la elección. Los resultados de 66 entrevistas semiestructuradas a padres y madres heterosexuales muestran que las madres son socialmente consideradas responsables de hijos e hijas, un factor clave para entender cómo España pasó del "baby boom" de las décadas 1950-1970 a la "infertilidad estructural" desde los años 1990

"I Want to Bury It, Will You Join Me?" : the Use of Ritual in Prenatal Loss among Women in Catalonia, Spain in the Early 21st Century

Prenatal loss, such as miscarriage and stillbirth, may be understood as the confluence of birth and death. The most significant of life's transitions, these events are rarely if ever expected to coincide. Although human cultures have long recognized death through ritual, it has not typically been used in cases of pregnancy loss. Interest in prenatal losses in the fields of medicine and the social sciences, as well as among the general public, has grown significantly in recent years in many countries, including Spain, as evidenced by increasing numbers of clinical protocols, academic books and articles, public events and popular media coverage. Even with this growing attention, there are still no officially sanctioned or generally accepted ways of using ritual to respond to prenatal losses in Spain. However, despite a lack of public recognition or acceptance of the use of ritual, we found that women in the autonomous community of Catalonia, in Spain, are employing ritual in various fashions, both with and without the support and acceptance of their family, friends or community, to process their losses and integrate them into their lives

Dones públiques, homes ocults

MEDEIROS, Regina Paula. Hablan las putas. Sobre prácticas sexuales preservativas y SIDA en el mundo de la prostitució

Dones públiques, homes ocults

Obra ressenyada: Regina Paula MEDEIROS, Hablan las putas. Sobre prácticas sexuales preservativas y SIDA en el mundo de la prostitució

La gobernanza de la(s) bioeconomía(s) : un proyecto político

Vicenzo PAVONE ; Joanna GOVEN. Bioeconomies: life, technology and capital in the 21st century. Cham: Palgrave Mcmillan, 201

Reseñas

Obra ressenyada: F. CHACÓN JIMÉNEZ, J. BESTARD-CAMPS, A. M. AGUADO, Familias : historia de la sociedad española (del final de la Edad Media a nuestros días). Madrid: Cátedra, 2011

Chacón Jiménez, F., Bestard-Camps, J., & Aguado, A. M. (2011). Familias : historia de la sociedad española (del final de la Edad Media a nuestros días). Madrid, Cátedra

Obra ressenyada: Chacón Jiménez, F., Bestard-Camps, J., & Aguado, A. M. (Coord.). Familias: historia de la sociedad española (del final de la Edad Media a nuestros días). Madrid, Cátedra, 2011