11. Expression patterns and prognostic relevance of subtype-specific transcription factors in surgically resected small cell lung cancer : an international multicenter studyZsolt Megyesfalvi, Nandor Barany, Andras Lantos, Zsuzsanna Valko, Orsolya Pipek, Christian Lang, Anna Schwendenwein, Felicitas Oberndorfer, Sandor Paku, Bence Ferencz, Izidor Kern, Mile Kovačević, Viktoria Laszlo, Balazs Dome, 2022, izvirni znanstveni članek Povzetek: The tissue distribution and prognostic relevance of subtype-specific proteins (ASCL1, NEUROD1, POU2F3, YAP1) present an evolving area of research in small cell lung cancer (SCLC). The expression of subtype-specific transcription factors and P53 and RB1 proteins were measured by immunohistochemistry (IHC) in 386 surgically resected SCLC samples. Correlations between subtype-specific proteins and in vitro efficacy of various therapeutic agents were investigated by proteomics and cell viability assays in 26 human SCLC cell lines. Besides SCLC-A (ASCL1-dominant), SCLC-AN (combined ASCL1/NEUROD1), SCLC-N (NEUROD1-dominant) and SCLC-P (POU2F3-dominant), IHC and cluster analyses identified a quadruple-negative SCLC subtype (SCLC-QN). No unique YAP1-subtype was found. The highest overall survival rates were associated with non-neuroendocrine subtypes (SCLC-P and SCLC-QN) and the lowest with neuroendocrine subtypes (SCLC-A, SCLC-N, SCLC-AN). In univariate analyses, high ASCL1 expression was associated with poor prognosis and high POU2F3 expression with good prognosis. Notably, high ASCL1 expression influenced survival outcomes independently of other variables in a multivariate model. High POU2F3 and YAP1 protein abundances correlated with sensitivity and resistance to standard-of-care chemotherapeutics, respectively. Specific correlation patterns were also found between the efficacy of targeted agents and subtype-specific protein abundances. In conclusion, we have investigated the clinicopathological relevance of SCLC molecular subtypes in a large cohort of surgically resected specimens. Differential IHC expression of ASCL1, NEUROD1 and POU2F3 defines SCLC subtypes. No YAP1-subtype can be distinguished by IHC. High POU2F3 expression is associated with improved survival in a univariate analysis, whereas elevated ASCL1 expression is an independent negative prognosticator. Proteomic and cell viability assays of human SCLC cell lines reveal distinct vulnerability profiles defined by transcription regulators.
Ključne besede: Non-small-cell lung carcinoma, immunohistochemistry, molecular subtypes, prognostic relevance, expression pattern, neuroendocrine subtypes
Objavljeno v DiRROS: 27.05.2022; Ogledov: 1069; Prenosov: 1330
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12. Consuming Eid Al-Adha : constructing and expressing the Muslim identityAmar Ahmed, 2020, izvirni znanstveni članek Povzetek: There is a lacuna in ethnographic research with regards to Muslims’ identity construction and expression from an internal perspective. Eid Al-Adha is an Islam-ic holiday which is rich in symbolism, collective rituals, and spiritual and material abundance. The article will interpret the meanings and values that consumers of Eid Al-Adha construct as parts of their identity, mainly being the religious one. It will discuss how the holiday expresses significant Muslim values like collectiv-ism, submission to God, sacrifice, charity, patience, and sacredness. Moreover, it will explain possible differences in consumption reflecting particularism due to national and/or cultural identities. The paper furthers our understanding of what Muslims do and say during their consumption of the Day rather than referring to scriptures or scholars. It contributes to the body of knowledge of Muslim holidays, the meanings associated with them, and how celebrators utilize the symbolism within them to construct their identities.
Ključne besede: Muslims, identity, Eid Al-Adha, consumer culture theory, Islamic culture, cultural consumption, identity construction, identity expression
Objavljeno v DiRROS: 19.05.2022; Ogledov: 686; Prenosov: 429
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13. Gene expression levels of the prolyl hydroxylase domain proteins PHD1 and PHD2 but not PHD3 are decreased in primary tumours and correlate with poor prognosis of patients with surgically resected non-small-cell lung cancerAna Koren, Matija Rijavec, Tomaž Krumpestar, Izidor Kern, Aleksander Sadikov, Tanja Čufer, Peter Korošec, 2021, izvirni znanstveni članek Povzetek: Background: Hypoxia correlates with poor prognosis in several cancer types, including lung cancer. Prolyl hydroxylase domain proteins (PHDs) play a role in cell oxygen sensing, negatively regulating the hypoxia-inducible factor (HIF) pathway. Our study aim was to evaluate PHD1, PHD2 and PHD3 mRNA expression levels in primary tumours and normal lungs of non-small-cell lung cancer (NSCLC) patients and to correlate it with selected regulators of HIF signalling, with clinicopathological characteristics and overall survival (OS). Methods: Tumour tissue samples were obtained from 60 patients with surgically resected NSCLC who were treated with radical surgery. In 22 out of 60 cases, matching morphologically normal lung tissue was obtained. PHD1, PHD2 and PHD3 mRNA expressions were measured using RT-qPCR. Results: The PHD1 and PHD2 mRNA levels in primary tumours were significantly decreased compared to those in normal lungs (both p < 0.0001). PHD1 and PHD2 expression in tumours was positively correlated (rs = 0.82; p < 0.0001) and correlated well with HIF pathway downstream genes HIF1A, PKM2 and PDK1. Decreased PHD1 and PHD2 were associated with larger tumour size, higher tumour stage (PHD1 only) and squamous cell carcinoma. Patients with low PHD1 and patients with low PHD2 expression had shorter OS than patients with high PHD1 (p = 0.02) and PHD2 expression (p = 0.01). PHD1 showed borderline independent prognostic values in multivariate analysis (p = 0.06). In contrast, we found no associations between PHD3 expression and any of the observed parameters. Conclusions: Our results show that reduced expression of PHD1 and PHD2 is associated with the development and progression of NSCLC. PHD1 could be further assessed as a prognostic marker in NSCLC.
Ključne besede: non-small-cell lung carcinoma, prognosis, non-small cell lung cancer, mRNA expression, prolyl hydroxylase domain proteins
Objavljeno v DiRROS: 21.05.2021; Ogledov: 1337; Prenosov: 929
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14. T2-high asthma, classified by sputum mRNA expression of IL4, IL5, and IL13, is characterized by eosinophilia and severe phenotypeMatija Rijavec, Tomaž Krumpestar, Sabina Škrgat, Izidor Kern, Peter Korošec, 2021, izvirni znanstveni članek Povzetek: Asthma is a common chronic disease, with different underlying inflammatory mechanisms. Identification of asthma endotypes, which reflect a variable response to different treatments, is important for more precise asthma management. T2 asthma is characterized by airway inflammation driven by T2 cytokines including interleukins IL-4, IL-5, and IL-13. This study aimed to determine whether induced sputum samples can be used for gene expression profiling of T2-high asthma classified by IL4, IL5, and IL13 expression. Induced sputum samples were obtained from 44 subjects, among them 36 asthmatic patients and eight controls, and mRNA expression levels of IL4, IL5, and IL13 were quantified by RT-qPCR. Overall, gene expression levels of IL4, IL5, and IL13 were significantly increased in asthmatic patients' samples compared to controls and there was a high positive correlation between expressions of all three genes. T2 gene mean was calculated by combining the expression levels of all three genes (IL4, IL5, and IL13) and according to T2 gene mean expression in controls, we set a T2-high/T2-low cutoff value. Twenty-four (67%) asthmatic patients had T2-high endotype and those patients had significantly higher eosinophil blood and sputum counts. Furthermore, T2-high endotype was characterized as a more severe, difficult-to-treat asthma, and often uncontrolled despite the use of inhaled and/or oral corticosteroids. Therefore, the majority of those patients (15 [63%] of 24) needed adjunct biological therapy to control their asthma symptoms/exacerbations. In conclusion, we found that interleukins IL4, IL5, and IL13 transcripts could be effectively detected in sputum from asthmatic patients. Implementation of T2 gene mean can be used as sputum molecular biomarker to categorize patients into T2-high endotype, characterized by eosinophilia and severe, difficult-to-treat asthma, and often with a need for biological treatment.
Ključne besede: asthma, gene expression, interleukin-4, interleukin-5, interleukin-13, severe asthma, endotype, IL-4, IL-5, IL-13, biologic treatment
Objavljeno v DiRROS: 02.02.2021; Ogledov: 1426; Prenosov: 910
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15. The impact of scald development on phenylpropanoid metabolism based on phenol content, enzyme activity, and gene expression analysisAnka Čebulj, Heidrun Halbwirth, Maja Mikulič Petkovšek, Robert Veberič, Ana Slatnar, 2020, izvirni znanstveni članek Ključne besede: scald, gene expression, hydroxycinnamic acids, color, enzyme activity, phenol content, scald development, apples, cold storage
Objavljeno v DiRROS: 03.09.2020; Ogledov: 1850; Prenosov: 579
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