المؤلفون: Ribera Salas, Jordi

المساهمون: University/Department: Universitat Autònoma de Barcelona. Departament de Medicina

مرشدي الرسالة: Zamora Plana, Lurdes, Ribera Santasusana, J. M. (José María)

المصدر: TDX (Tesis Doctorals en Xarxa)

مصطلحات موضوعية: Leucèmia aguda limfoblàstica, Leucemia aguda linfoblástica, Acute lymphoblastic leukemia, Marcadros pronòstic, Marcadores pronóstico, Prognostic markers, Alteracions genètiques, Alteraciones genéticas, Genetic alterations, Ciències de la Salut

الوصف: El 75% de los pacientes con leucemia aguda linfoblástica (LAL) tiene alteraciones cromosómicas recurrentes (numéricas o estructurales). Dichas anomalías (alteraciones primarias) tienen valor pronóstico independiente de otras variables y ello se tiene en cuenta para administrar un tratamiento adaptado al riesgo de cada leucemia. Sin embargo, el impacto pronóstico que pueden tener las alteraciones secundarias (p.ej. mutaciones puntuales o alteraciones en el número de copias) no está tan claro. Es probable que éstas jueguen un papel importante en la respuesta al tratamiento, ya que no todos los pacientes con el mismo cariotipo responden igual a la terapia. Con el fin de identificar nuevos marcadores pronósticos en la LAL de línea B, se ha analizado la frecuencia y significado pronóstico de las alteraciones en el número de copias (CNA) en muestras de pacientes de LAL B madura y LAL de precursores B. En el primer trabajo de esta Tesis Doctoral se identificaron las deleciones de los genes EBF1, IKZF1 y CDKN2A/B como factores pronósticos independientes en una serie de 142 pacientes adolescentes y adultos de LAL de precursores B analizados en el momento del diagnóstico. Concretamente, las deleciones de EBF1 se asociaron con una menor probabilidad de alcanzar la remisión completa, las deleciones de IKZF1 se relacionaron con una mayor probabilidad de sufrir una recaída de la enfermedad, mientras que las deleciones de CDKN2A/B estaban presentes en pacientes con menor probabilidad de supervivencia global. Por tanto, la detección de estas alteraciones genéticas identifica un subgrupo de pacientes con LAL de alto riesgo, los cuales podrían beneficiarse de tratamientos más intensivos, a la espera de tratamientos más específicos contra dichas alteraciones. En el segundo trabajo se evidenció que las LAL de precursores B y las LAL B maduras tienen un perfil genético diferente. En este sentido, la frecuencia de alteraciones de mal pronóstico identificadas en el primer trabajo fue mucho menor en los pacientes con LAL B madura que en los pacientes con LAL de precursores B. Este hecho podría explicar, en parte, el mejor pronóstico que muestran las LAL B maduras en comparación con las de precursores B. Sin embargo, pese a que se detectaron deleciones potencialmente relacionadas con la agresividad y diseminación de las LAL B maduras (CDKN2A/B, RB1 y región 14q32.33), no se consiguió identificar ninguna CNA con valor pronóstico en estos pacientes. Finalmente, en el tercer trabajo se analizaron muestras en recaída de pacientes con LAL de precursores B. Mediante la comparación de muestras pareadas de diagnóstico y recaída de cada paciente se observó un aumento significativo del número de CNA durante la progresión de la leucemia. Además, se evidenció una gran diversidad de rutas metabólicas afectadas por CNA, sin que se detectara una firma genética recurrente en recaída, a excepción de la adquisición de deleciones homocigotas en el gen CDKN2A/B (frecuencia del ~50%). Las rutas metabólicas más afectadas en recaída fueron las que afectan a la diferenciación de los linfocitos B, al control del ciclo celular y a la apoptosis, entre otras. Las alteraciones en genes involucrados en la proliferación celular, la homeostasis de las células madre hematopoyéticas y la resistencia a fármacos fueron las más comunes entre las CNA adquiridas de novo en recaída. A excepción de una paciente, todos los pacientes mostraron cambios genéticos respecto al diagnóstico y la mayoría de recaídas provenían de un clon ancestral al detectado en el momento del diagnóstico. La identificación de CNA específicas de recaída puede contribuir a diseñar nuevos tratamientos que aumenten la probabilidad de supervivencia de los pacientes en esta situación, que actualmente es de tan sólo el 10%.

الوصف (مترجم): Approximately, 75% of acute lymphoblastic leukemia (ALL) patients show recurrent chromosomal abnormalities (numerical and structural). These are primary alterations that have been extensively related to patients’ prognosis. The predictive value of these chromosomal aberrations is taken into account for treatment assignment. However, the prognostic value of secondary alterations (i.e., point mutations or copy number alterations) is less clear. These alterations may play an important role in the response to the therapy, as not all patients with the same karyotype show the same response to treatment. With the aim to identify new prognostic markers in patients with B lineage ALL, the frequency and prognostic significance of copy number alterations (CNA) in patients with mature and precursor B ALL have been analyzed. In the first study of this Doctoral Thesis EBF1, IKZF1 and CDKN2A/B deletions at diagnosis were identified as markers with independent prognostic value in a series of 142 adolescent and adult patients with precursor B ALL. Specifically, EBF1 deletions were associated with a lower probability of achieving complete remission, IKZF1 deletions were related to a greater relapse probability while CDKN2A/B deletions were present in patients with lower survival probability. Therefore, the detection of these genetic alterations identifies a subset of high risk patients who may benefit from a more intensive treatment, while new and more specific treatments are developed against these alterations. In the second study, a clear difference in the genetic profiles of mature B and precursor B ALL was observed. In this sense, the frequency of the alterations associated with poor prognosis detected in the first study was much lower in mature B ALL compared to precursor B ALL patients. This fact may explain, in part, the better prognosis of mature B compared to that of precursor B ALL. However, although some deletions potentially related to the aggressiveness and dissemination of mature B ALL (CDKN2A / B, RB1 and 14q32.33 region) were detected, no CNAs with prognostic value could be identified in these patients. Finally, relapse samples of patients with precursor B ALL were analyzed in the third study. Comparison of paired diagnostic and relapse samples from each patient showed a significant increase in the number of CNAs during the progression of leukemia. In addition, a great diversity of metabolic pathways affected by CNA without a recurrent genetic signature at relapse was evidenced, except for the acquisition of homozygous deletions in the CDKN2A/B gene (~50% frequency). The most frequently involved metabolic pathways at relapse were those related with differentiation of B lymphocytes, cell cycle control and apoptosis, among others. Alterations in genes involved in cell proliferation, hematopoietic stem cell homeostasis, and drug resistance were the most common among the newly acquired CNAs at relapse. With the exception of one patient, all patients showed at relapse genetic changes compared to the diagnosis and most relapses came from an ancestral clone to that detected at the time of diagnosis. The identification of relapse-specific CNAs may contribute to the design of new treatments that could increase the probability of survival of relapsed patients, which currently stands at 10%.

وصف الملف: application/pdf

الوصول الحر: http://hdl.handle.net/10803/456036Test

المؤلفون: Willis, Joseph, Anders, Robert, Torigoe, Toshihiko, Hirohashi, Yoshihiko, Bifulco, Carlo, Zlobec, Inti, Mlecnik, Bernhard, Demaria, Sandra, Choi, Won-Tak, Dundr, Pavel, Tatangelo, Fabiana, Di Mauro, Annabella, Baldin, Pamela, Bindea, Gabriela, Marliot, Florence, Haicheur, Nacilla, Fredriksen, Tessa, Kirilovsky, Amos, Buttard, Bénédicte, Vasaturo, Angela, Lafontaine, Lucie, Maby, Pauline, El Sissy, Carine, Hijazi, Assia, Majdi, Amine, Lagorce, Christine, Berger, Anne, Van den Eynde, Marc, Pagès, Franck, Lugli, Alessandro, Galon, Jérôme

المصدر: Cancers. 15(16)

مصطلحات موضوعية: T cell, anatomopathology, colon cancer, digital pathology, immunoscore, prognostic markers, risk stratification, tumor microenvironment

الوصف: BACKGROUND: The Immunoscore (IS) is a quantitative digital pathology assay that evaluates the immune response in cancer patients. This study reports on the reproducibility of pathologists visual assessment of CD3+- and CD8+-stained colon tumors, compared to IS quantification. METHODS: An international group of expert pathologists evaluated 540 images from 270 randomly selected colon cancer (CC) cases. Concordance between pathologists T-score, corresponding hematoxylin-eosin (H&E) slides, and the digital IS was evaluated for two- and three-category IS. RESULTS: Non-concordant T-scores were reported in more than 92% of cases. Disagreement between semi-quantitative visual assessment of T-score and the reference IS was observed in 91% and 96% of cases before and after training, respectively. Statistical analyses showed that the concordance index between pathologists and the digital IS was weak in two- and three-category IS, respectively. After training, 42% of cases had a change in T-score, but no improvement was observed with a Kappa of 0.465 and 0.374. For the 20% of patients around the cut points, no concordance was observed between pathologists and digital pathology analysis in both two- and three-category IS, before or after training (all Kappa < 0.12). CONCLUSIONS: The standardized IS assay outperformed expert pathologists T-score evaluation in the clinical setting. This study demonstrates that digital pathology, in particular digital IS, represents a novel generation of immune pathology tools for reproducible and quantitative assessment of tumor-infiltrated immune cell subtypes.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/5p41c8z2Test

المؤلفون: Godina, Christopher, Belting, Mattias, Vallon-Christersson, Johan, Isaksson, Karolin, Bosch, Ana, Jernström, Helena

المصدر: Scientific Reports. 14

مصطلحات موضوعية: Caveolin-1, Breast cancer, Molecular profiling, Prognostic markers, PAM50 ROR

الوصف: Combining information from the tumor microenvironment (TME) with PAM50 Risk of Recurrence (ROR) score could improve breast cancer prognostication. Caveolin-1 (CAV1) is a marker of an active TME. CAV1 is a membrane protein involved in cell signaling, extracellular matrix organization, and tumor-stroma interactions. We sought to investigate CAV1 gene expression in relation to PAM50 subtypes, ROR score, and their joint prognostic impact. CAV1 expression was compared between PAM50 subtypes and ROR categories in two cohorts (SCAN-B, n = 5326 and METABRIC, n = 1980). CAV1 expression was assessed in relation to clinical outcomes using Cox regression and adjusted for clinicopathological predictors. Effect modifications between CAV1 expression and ROR categories on clinical outcome were investigated using multiplicative and additive two-way interaction analyses. Differential gene expression and gene set enrichment analyses were applied to compare high and low expressing CAV1 tumors. All samples expressed CAV1 with the highest expression in the Normal-like subtype. Gene modules consistent with epithelial-mesenchymal transition (EMT), hypoxia, and stromal activation were associated with high CAV1 expression. CAV1 expression was inversely associated with ROR category. Interactions between CAV1 expression and ROR categories were observed in both cohorts. High expressing CAV1 tumors conferred worse prognosis only within the group classified as ROR high. ROR gave markedly different prognostic information depending on the underlying CAV1 expression. CAV1, a potential mediator between the malignant cells and TME, could be a useful biomarker that enhances and further refines PAM50 ROR risk stratification in patients with ROR high tumors and a potential therapeutic target.

وصف الملف: electronic

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-527042Test
https://doi.org/10.1038/s41598-024-57365-8Test
https://uu.diva-portal.org/smash/get/diva2:1854638/FULLTEXT01.pdfTest

المؤلفون: Ah Ran Oh, Ji-Hye Kwon, Gayoung Jin, So Myung Kong, Dong Jae Lee, Jungchan Park

المصدر: Scientific Reports, Vol 14, Iss 1, Pp 1-11 (2024)

مصطلحات موضوعية: Inflammation markers, Mortality, Hip replacement, Surgical outcomes, Prognostic markers, Medicine, Science

الوصف: Abstract We aimed to evaluate the association between inflammation-based prognostic markers and mortality after hip replacement. From March 2010 to June 2020, we identified 5,369 consecutive adult patients undergoing hip replacement with C-reactive protein (CRP), albumin, and complete blood count measured within six months before surgery. Receiver operating characteristic (ROC) curves were generated to evaluate predictabilities and estimate thresholds of CRP-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). Patients were divided according to threshold, and mortality risk was compared. The primary outcome was one-year mortality, and overall mortality was also analyzed. One-year mortality was 2.9%. Receiver operating characteristics analysis revealed areas under the curve of 0.838, 0.832, 0.701, and 0.732 for CAR, NLR, PLR, and modified Glasgow Prognostic Score, respectively. The estimated thresholds were 2.10, 3.16, and 11.77 for CAR, NLR, and PLR, respectively. According to the estimated threshold, high CAR and NLR were associated with higher one-year mortality after adjustment (1.0% vs. 11.7%; HR = 2.16; 95% CI 1.32–3.52; p = 0.002 for CAR and 0.8% vs. 9.6%; HR = 2.05; 95% CI 1.24–3.39; p = 0.01 for NLR), but PLR did not show a significant mortality increase (1.4% vs. 7.4%; HR = 1.12; 95% CI 0.77–1.63; p = 0.57). Our study demonstrated associations of preoperative levels of CAR and NLR with postoperative mortality in patients undergoing hip replacement. Our findings may be helpful in predicting mortality in patients undergoing hip replacement.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/c12a82d12b8440299333f3f6fc501fe2Test

المؤلفون: J. Bhaskari, Rahul Bhagat, V. Shilpa, C.S. Premalata, Lakshmi Krishnamoorthy

المصدر: Journal of Ovarian Research, Vol 17, Iss 1, Pp 1-11 (2024)

مصطلحات موضوعية: VEGF-C, COX-2, Ki-67, eNOS-nitric oxide, Epithelial ovarian cancers, Prognostic markers., Gynecology and obstetrics, RG1-991

الوصف: Abstract Purpose Our explorative study assessed a panel of molecules for their association with epithelial ovarian carcinomas and their prognostic implications. The panel included tissue expression of VEGF-C, COX-2, Ki-67 and eNOS alongside plasma levels of VEGF-C and nitric oxide. Methods 130 cases were enrolled in the study. Plasma levels were quantified by ELISA and tissue expressions were scored by immunohistochemistry. The Chi square and Fischer’s exact test were applied to examine the impact of markers on clinicopathological factors. Non-parametric Spearman’s rank correlation test was applied to define the association among test factors. Results Plasma VEGF-C levels and COX-2 tissue expression strongly predicted recurrence and poor prognosis (

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1757-2215Test

الوصول الحر: https://doaj.org/article/b419d8967f3f4bbeb255821c70f613a2Test

المؤلفون: Christopher Godina, Mattias Belting, Johan Vallon-Christersson, Karolin Isaksson, Ana Bosch, Helena Jernström

المصدر: Scientific Reports, Vol 14, Iss 1, Pp 1-14 (2024)

مصطلحات موضوعية: Caveolin-1, Breast cancer, Molecular profiling, Prognostic markers, PAM50 ROR, Medicine, Science

الوصف: Abstract Combining information from the tumor microenvironment (TME) with PAM50 Risk of Recurrence (ROR) score could improve breast cancer prognostication. Caveolin-1 (CAV1) is a marker of an active TME. CAV1 is a membrane protein involved in cell signaling, extracellular matrix organization, and tumor-stroma interactions. We sought to investigate CAV1 gene expression in relation to PAM50 subtypes, ROR score, and their joint prognostic impact. CAV1 expression was compared between PAM50 subtypes and ROR categories in two cohorts (SCAN-B, n = 5326 and METABRIC, n = 1980). CAV1 expression was assessed in relation to clinical outcomes using Cox regression and adjusted for clinicopathological predictors. Effect modifications between CAV1 expression and ROR categories on clinical outcome were investigated using multiplicative and additive two-way interaction analyses. Differential gene expression and gene set enrichment analyses were applied to compare high and low expressing CAV1 tumors. All samples expressed CAV1 with the highest expression in the Normal-like subtype. Gene modules consistent with epithelial-mesenchymal transition (EMT), hypoxia, and stromal activation were associated with high CAV1 expression. CAV1 expression was inversely associated with ROR category. Interactions between CAV1 expression and ROR categories were observed in both cohorts. High expressing CAV1 tumors conferred worse prognosis only within the group classified as ROR high. ROR gave markedly different prognostic information depending on the underlying CAV1 expression. CAV1, a potential mediator between the malignant cells and TME, could be a useful biomarker that enhances and further refines PAM50 ROR risk stratification in patients with ROR high tumors and a potential therapeutic target.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/97f3d582073e472a88a489644135df4aTest

المؤلفون: Sen Qiao, Fengming Wu, Hongmei Wang

المصدر: Cancer Reports, Vol 7, Iss 6, Pp n/a-n/a (2024)

مصطلحات موضوعية: bioinformatic, pancreatic adenocarcinoma, prognostic markers, transient receptor potential channel, TRPM8, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract Background Pancreatic adenocarcinoma (PAAD), a member of highly lethal malignant tumors, has a poor outcome and extremely poor prognosis. The transient receptor potential (TRP) superfamily, a group of nonselective cation channels, is capable of influencing cellular functions by regulating calcium homeostasis. In addition, it has been shown that TRP channels can also affect various cellular phenotypes by regulating gene transcription levels and are involved in the development of a variety of malignant tumors. Aims In order to find new therapeutic targets and biomarkers to improve the clinical prognosis of pancreatic cancer, we performed genetic and immunological characterization of TRP channels in PAAD, as well as related functional and prognostic analyses. Methods and Results We investigated the expression, genetic alterations, methylation levels, and immune infiltration levels of TRP channels in PAAD, and further also analyzed the function of TRP channels in PAAD and their prognostic value for PAAD patients. Our results suggest that TRPM8 may contribute to tumor proliferation by controlling the PI3K‐AKT–mTOR signaling pathway in PAAD. Conclusion After careful evaluation of the accumulated data, we concluded that TRPM8 has potential as a prognostic indicator and prospective therapeutic target in PAAD.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2573-8348Test

الوصول الحر: https://doaj.org/article/c317823c36ce4085bf38334ff97df96bTest

المؤلفون: Jian Deng, ShengYuan Tu, Lin Li, GangLi Li, YinHui Zhang

المصدر: Cancer Reports, Vol 7, Iss 6, Pp n/a-n/a (2024)

مصطلحات موضوعية: biomarkers, clear cell renal cell carcinoma, diagnostic markers, predictive markers, prognostic markers, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract Clear cell renal cell carcinoma (ccRCC) is a common and aggressive subtype of kidney cancer. Many patients are diagnosed at advanced stages, making early detection crucial. Unfortunately, there are currently no noninvasive tests for ccRCC, emphasizing the need for new biomarkers. Additionally, ccRCC often develops resistance to treatments like radiotherapy and chemotherapy. Identifying biomarkers that predict treatment outcomes is vital for personalized care. The integration of artificial intelligence (AI), multi‐omics analysis, and computational biology holds promise in bolstering detection precision and resilience, opening avenues for future investigations. The amalgamation of radiogenomics and biomaterial‐basedimmunomodulation signifies a revolutionary breakthrough in diagnostic medicine. This review summarizes existing literature and highlights emerging biomarkers that enhance diagnostic, predictive, and prognostic capabilities for ccRCC, setting the stage for future clinical research.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2573-8348Test

الوصول الحر: https://doaj.org/article/b8d39c14160a4885874a88a7195b325dTest

المؤلفون: Chao Song, Ganggang Wang, Mengmeng Liu, Zijin Xu, Xin Liang, Kai Ding, Yu Chen, Wenquan Wang, Wenhui Lou, Liang Liu

المصدر: Heliyon, Vol 10, Iss 9, Pp e29914- (2024)

مصطلحات موضوعية: Pancreatic cancer, Whole-genome DNA methylation, TCGA database, Methylation driver genes, Prognostic risk prediction model, Prognostic markers, Science (General), Q1-390, Social sciences (General), H1-99

الوصف: This study was based on the use of whole-genome DNA methylation sequencing technology to identify DNA methylation biomarkers in tumor tissue that can predict the prognosis of patients with pancreatic cancer (PCa). TCGA database was used to download PCa-related DNA methylation and transcriptome atlas data. Methylation driver genes (MDGs) were obtained using the MethylMix package. Candidate genes in the MDGs were screened for prognostic relevance to PCa patients by univariate Cox analysis, and a prognostic risk score model was constructed based on the key MDGs. ROC curve analysis was performed to assess the accuracy of the prognostic risk score model. The effects of PIK3C2B knockdown on malignant phenotypes of PCa cells were investigated in vitro. A total of 2737 differentially expressed genes were identified, with 649 upregulated and 2088 downregulated, using 178 PCa samples and 171 normal samples. MethylMix was employed to identify 71 methylation-driven genes (47 hypermethylated and 24 hypomethylated) from 185 TCGA PCa samples. Cox regression analyses identified eight key MDGs (LEF1, ZIC3, VAV3, TBC1D4, FABP4, MAP3K5, PIK3C2B, IGF1R) associated with prognosis in PCa. Seven of them were hypermethylated, while PIK3C2B was hypomethylated. A prognostic risk prediction model was constructed based on the eight key MDGs, which was found to accurately predict the prognosis of PCa patients. In addition, the malignant phenotypes of PANC-1 cells were decreased after the knockdown of PIK3C2B. Therefore, the prognostic risk prediction model based on the eight key MDGs could accurately predict the prognosis of PCa patients.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2405844024059450Test; https://doaj.org/toc/2405-8440Test

الوصول الحر: https://doaj.org/article/0da8404543c84041822b36ce2496ade7Test

المؤلفون: Mariacristina Amato, Simona Santonocito, Maria Teresa Bruno, Alessandro Polizzi, Alessandro Mastroianni, Akhilanand Chaurasia, Gaetano Isola

المصدر: Heliyon, Vol 10, Iss 10, Pp e31061- (2024)

مصطلحات موضوعية: Human papilloma virus, Oral cell, Oral mucosa, Periodontitis, Prognostic markers, Science (General), Q1-390, Social sciences (General), H1-99

الوصف: Human Papilloma Virus (HPV) is considered one of the most common sexually transmitted infections and has been shown to play an important role in the pathogenesis of squamous cell carcinomas (SCC) of the cervix and head and neck. Manifestations of HPV infections can be manifold, ranging from asymptomatic infections to benign or potentially malignant lesions to intraepithelial neoplasms and invasive carcinomas. The heterogeneity of clinical manifestations from HPV infection depends on the interactions between the viral agent and the host, a direct consequence of the ability on the part of HPV is to remain silent and to evade and convey the action of the host immune system. The oral mucosa represents one of the tissues for which HPV has a distinct tropism and is frequently affected by infection. While much information is available on the role that HPV infection plays in the development of SCC in the oral cavity, there is less information on asymptomatic infections and benign HPV-induced oral lesions. Therefore, the purpose of this review is to analyze, in light of current knowledge, the early clinical and bio-humoral prognostic features related to the risk of HPV malignant transformation, focusing on subclinical conditions, benign lesions, and the correlation between oral infection and infection in other districts. The data show that the main risk associated with HPV infection is related to malignant transformation of lesions. Although HPV-driven OPSCC is associated with a better prognosis than non-HPV-driven OPSCC, primary prevention and early detection of the infection and affected genotype are essential to reduce the risk of malignant neoplastic complications and improve the prognosis.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2405844024070920Test; https://doaj.org/toc/2405-8440Test

الوصول الحر: https://doaj.org/article/f2c23d0a79c04e6f96f03a28226b5be0Test