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Background/aim: LUNGBANK was established as part of Project LUNGMARK, pioneering a biorepository dedicated exclusively to lung cancer research. It employs cutting-edge technologies to streamline the handling of biospecimens, ensuring the acquisition of high-quality samples. This infrastructure is fortified with robust data management capabilities, enabling seamless integration of diverse datasets. LUNGBANK functions not merely as a repository but as a sophisticated platform crucial for advancing lung cancer research, poised to facilitate significant discoveries. Materials and methods: LUNGBANK was meticulously designed to optimize every stage of biospecimen handling, from collection and storage to processing. Rigorous standard operating procedures and stringent quality control measures guarantee the integrity of collected biospecimens. Advanced data management protocols facilitate the efficient integration and analysis of various datasets, enhancing the depth and breadth of research possibilities in lung cancer. Results: LUNGBANK has amassed a comprehensive collection of biospecimens essential for unraveling the intricate molecular mechanisms of lung cancer. The integration of state-of-the-art technologies ensures the acquisition of top-tier data, fostering breakthroughs in translational and histological research. Moreover, the establishment of patient-derived systems by LUNGBANK underscores its pivotal role in personalized medicine approaches. Conclusion: The establishment of LUNGBANK marks a significant milestone in addressing the critical challenges of lung cancer research. By providing researchers with high-quality biospecimens and advanced research tools, LUNGBANK not only supports Project LUNGMARK's objectives but also contributes extensively to the broader landscape of personalized medicine. It promises to enhance our understanding of lung cancer initiation, progression, and therapeutic interventions tailored to individual patient needs, thereby advancing the field towards more effective diagnostic and therapeutic strategies.

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Systems biology adopted functional and integrative multiomics approaches enable to discover the whole set of interacting regulatory components such as genes, transcripts, proteins, metabolites, and metabolite dependent protein modifications. This interactome build up the midpoint of protein-protein/PTM, protein-DNA/RNA, and protein-metabolite network in a cell. As the key drivers in cellular metabolism, metabolites are precursors and regulators of protein post-translational modifications [PTMs] that affect protein diversity and functionality. The precisely orchestrated core pattern of metabolic networks refer to paradigm 'metabolites regulate PTMs, PTMs regulate enzymes, and enzymes modulate metabolites' through a multitude of feedback and feed-forward pathway loops. The concept represents a flawless PTM-metabolite-enzyme(protein) regulomics underlined in reprogramming cancer metabolism. Immense interconnectivity of those biomolecules in their spectacular network of intertwined metabolic pathways makes integrated proteomics and metabolomics an excellent opportunity, and the central component of integrative multiomics framework. It will therefore be of significant interest to integrate global proteome and PTM-based proteomics with metabolomics to achieve disease related altered levels of those molecules. Thereby, present update aims to highlight role and analysis of interacting metabolites/oncometabolites, and metabolite-regulated PTMs loop which may function as translational monitoring biomarkers along the reprogramming continuum of oncometabolism.

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Lung cancer is the leading cancer type of death rate. The lung adenocarcinoma subtype is responsible for almost half of the total lung cancer deaths. Despite the improvements in cancer treatment in recent years, lung adenocarcinoma patients' overall survival rate remains poor. Immunetherapy and chemotherapy are two of the most widely used options for the treatment of cancer. Although many cancer types initially respond to these treatments, the development of resistance is inevitable. The rapid development of drug resistance mainly characterizes lung adenocarcinoma. Despite being the subject of many studies in recent years, the resistance initiation and progression mechanism is still unclear. In this review, we have examined the role of the primary DNA repair pathways (non-homologous end joining (NHEJ) pathway, homologous-recombinant repair (HR) pathway, base excision repair (BER) pathway, and nucleotide excision repair (NER) pathway and transactivation mechanisms of tumor protein 53 (TP53) in drug resistance development. This review suggests that mentioned pathways have essential roles in developing the resistance against chemotherapy and immunotherapy in lung adenocarcinoma patients.

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Metabolomics offers new promise for research on prostate cancer (PCa) and its personalized treatment. Metabolomic profiling of radiation-treated PCa patients is particularly important to reveal their new metabolomic status, and evaluate the radiation effects. In addition, bioinformatics-integrated metabolomics-based approaches for disease profiling and assessment of therapy could help develop precision biomarkers in a context of PCa. We report mass spectrometry-based untargeted (global) serum metabolomics findings from patients with PCa (n = 55) before and after treatment with stereotactic body radiation therapy (SBRT), and intensity-modulated radiation therapy (IMRT) with SBRT, and using parsimony phylogenetic analysis. Importantly, the radiation-treated serum metabolome of patients represented a unique robust cluster on a cladogram that was distinct from the pre-RT metabolome. The altered radiation responsive serum metabolome was defined by predominant aberrations in the metabolic pathways of nitrogen, pyrimidine, purine, porphyrin, alanine, aspartate, glutamate, and glycerophospholipid. Our findings collectively suggest that global metabolomics integrated with parsimony phylogenetics offer a unique and robust systems biology analytical platform for powerful unbiased determination of radiotherapy (RT)-associated biosignatures in patients with PCa. These new observations call for future translational research for evaluation of metabolomic biomarkers in PCa prognosis specifically, and response to radiation treatment broadly. Radiation metabolomics is an emerging specialty of systems sciences and clinical medicine that warrants further research and educational initiatives.

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INTRODUCTION: Chronic myeloproliferative disorders (CMPD) are chronic myeloid hematological disorders, characterized by increased myeloid cell proliferation and fibrosis. Impaired apoptotic mechanisms, increased cell proliferation, uncontrolled hematopoietic cell proliferation and myeloaccumulation may contribute to the pathogenesis of CMPD. The aim of our study was to show the possible role of FAS/FASL gene polymorphisms in CMPD pathogenesis and investigate the association with clinical parameters and susceptibility to disease. MATERIAL AND METHODS: We included 101 (34 polycythemia vera (PV), 23 primary myelofibrosis (PMF), 44 essential thrombocythemia (ET)) CMPD patients diagnosed according to the WHO classification criteria and 95 healthy controls in this study. All the patients and the controls were investigated for FAS/FASL gene expression, allele frequencies and phenotype features, and also FAS mRNA levels were analyzed. RESULTS: Chronic myeloproliferative disorders patients showed increased FAS-670AG + GG genotype distribution compared with the control group (p < 0.05). While the A allele was more frequent in both groups, AG genotype was more frequent in CMPD patients. There was no association between FAS-670A>G gene polymorphism and some clinical parameters such as splenomegaly and thrombosis (p > 0.05). No statistically significant difference in FASL+843C>T genotype or allele frequency was found between groups (p > 0.05). Moreover, no statistically significant difference was detected in FASL and JAK2V617F mutations (p > 0.05). FAS mRNA expression was 1.5-fold reduced in patients compared to healthy subjects. CONCLUSIONS: According to our findings, FAS/FASL gene expression may contribute to the molecular and immunological pathogenesis of CMPD. More investigations are needed to support these data.

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Pancreatic ductal adenocarcinoma (PDAC) is one of the rapidly growing forms of pancreatic cancer with a poor prognosis and less than 5% 5-year survival rate. In this study, we characterized the genetic signatures and signaling pathways related to survival from PDAC, using a parsimony phylogenetic algorithm. We applied the parsimony phylogenetic algorithm to analyze the publicly available whole-genome in silico array analysis of a gene expression data set in 25 early-stage human PDAC specimens. We explain here that the parsimony phylogenetics is an evolutionary analytical method that offers important promise to uncover clonal (driver) and nonclonal (passenger) aberrations in complex diseases. In our analysis, parsimony and statistical analyses did not identify significant correlations between survival times and gene expression values. Thus, the survival rankings did not appear to be significantly different between patients for any specific gene (p > 0.05). Also, we did not find correlation between gene expression data and tumor stage in the present data set. While the present analysis was unable to identify in this relatively small sample of patients a molecular signature associated with pancreatic cancer prognosis, we suggest that future research and analyses with the parsimony phylogenetic algorithm in larger patient samples are worthwhile, given the devastating nature of pancreatic cancer and its early diagnosis, and the need for novel data analytic approaches. The future research practices might want to place greater emphasis on phylogenetics as one of the analytical paradigms, as our findings presented here are on the cusp of this shift, especially in the current era of Big Data and innovation policies advocating for greater data sharing and reanalysis.

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Henoch-Schönlein purpura (HSP) is a small-vessel vasculitis of autoimmune hypersensitivity with rash, arthritis, abdominal pain and renal involvements. Macrophage migration inhibitory factor (MIF) is a immunoregulatory proinflammatory cytokine, and a major mediator at the inflammatory sites. The pathogenesis of HSP has not been fully elucidated. Here we aimed to assess the influence of macrophage migration inhibitory factor gene (-173 G/C) polymorphism in the susceptibility and clinical expression of patients with Henoch-Schönlein purpura (HSP). HSP patients (n:139) and ethnically matched healthy controls (n:100) were genotyped by PCR-RFLP. Genotype analysis of both polymorphisms did not reveal a significant deviation from Hardy-Weinberg equilibrium in any group (p > 0.05). No significant difference was obtained in genotype distribution (p > 0.05) and allele frequencies (p > 0.05) between patients and controls. A statistically significant genotype-phenotype correlation was not obtained when HSP patients were stratified by the presence of certain systemic complications and the macrophage migration inhibitory factor gene (-173 G/C) polymorphism (p > 0.05). A significant risk was not observed in the subjects both with the GC+CC genotype (p = 0.06, OR: 0.5538, 95% CI: 0.2985-1.0274) and C allele (odds ratio: C vs. G: 1.799, 95% CI: 1.002-3.23, p = 0.05). Our findings suggest that MIF gene -173 G/C polymorphism is not associated with HSP in the present Turkish population.

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Henoch-Schönlein purpura (HSP) is a small-vessel vasculitis of autoimmune hypersensitivity, and renin-angiotensin system (RAS) regulates vascular homeostasis and inflammation with activation of cytokine release. Thus, we aimed to investigate the association between HSP and ACE I/D and AGT M235T polymorphisms. Genotyping was determined by allele specific PCR and PCR-RFLP. We obtained a significant difference in genotype distribution (p=0.003) and allele frequencies (p<0.001) of ACE I/D polymorphism between patients and controls, while no significant association was detected in genotype distribution (p> 0.05) and allele frequencies (p> 0.05) of the AGT M235T polymorphism. Risk assessment showed significant risk for HSP in the subjects both with the ID + DD genotype (p=0.019, OR: 2.288, 95% CI: 1.136-4.609) and D allele (OR: D vs. I: 2.0528, 95% CI: 1.3632-3.0912, p=0.001) while no significant risk was obtained for HSP in the subjects both with the MT + TT genotype (p=0.312, OR: 1.3905, 95% T vs. M: 1.065, 95% CI: 0.7326-2.6391) and T allele (OR: patients were stratified by the presence of certain systemic complications of HSP, no significant association was detected with ACE I/D, and AGT M235T polymorphisms. Our findings suggest that ACE I/D polymorphism is significantly associated with HSP susceptibility.

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Retinitis pigmentosa (RP) is an inherited progressive retinal disease with a complex inheritance pattern affecting about 1 in 3,500 people worldwide. To date, a large number of sequence changes in the causal contributor genes of wide-spectrum heterogeneous RP were reported, including deletions, insertions, or substitutions that lead missense mutations or truncations. Here we present an association between the clinical presentations of adRP and sequence variants involving novel M216L mutation in the RHO gene together with nonsynonimous sequence changes R872H, N985Y, A1670T, S1691P, C2033Y, and synonimous Q1725Q with novel, N1521N, and T1733T SNPs in the RP1 gene of uncertain pathogenicity in a Turkish family with autosomal dominant retinitis pigmentosa.

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Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disorder characterized by episodes of inflammation in the absence of high-titer autoantibodies or antigen-specific T cells. The Mediterranean fever (MEFV) gene located on chromosome 16p13.3, which encodes the 781-amino-acid protein pyrin, is the causative gene for this monogenic Mendelian disease. This study presents the molecular analysis of an MEFV gene mutation screen of 5518 Turkish individuals with clinical diagnoses of FMF. Patients were genetically diagnosed using the FMF StripAssay and DNA sequencing analysis. Contrary to the results achieved by the FMF StripAssay, DNA sequencing analysis identified large-scale coding and noncoding novel sequence variants, together with a significant group (76%) of individuals who were receiving colchicine and had a single heterozygous mutation, despite the recessive inheritance of FMF. In conclusion, sequence analysis, unlike other routine laboratory techniques, may enable screening for a broad range of nucleotide variations and may prevent less common, population-restricted, novel sequence variants from being overlooked.

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