Genomic analysis in short- and long-term patients with malignant pleura mesothelioma treated with palliative chemotherapy

Torricelli, Federica; Saxena, Alka; Nuamah, Rosamond; Neat, Michael; Harling, Leanne; Ng, Wen; Spicer, James; Ciarrocchi, Alessia; Billè, Andrea

doi:10.1016/j.ejca.2020.03.002

Cited by 6 publications

(5 citation statements)

References 24 publications

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“…The same genes were also described in the RAMES study where RDX and MXRA5 represented the 42% and 23% of MPMs, respectively, however in this case MXRA5 was identified in both epithelioid and non-epithelioid histotypes (144). Moreover, the same gene is reported to be significantly correlated to longer survival rate in a cohort of epithelioid only MPMs (145). Therefore, although the correlation of MXRA5 to histopathologic or clinical features needs further interpretation, more studies on this gene and RDX are warranted.…”

Section: Therapeutic Implications Of Genomics and Transcriptomics Evidencessupporting

confidence: 68%

Tumor Immune Microenvironment and Genetic Alterations in Mesothelioma

et al. 2021

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Malignant pleural mesothelioma (MPM) is a rare and fatal disease of the pleural lining. Up to 80% of the MPM cases are linked to asbestos exposure. Even though its use has been banned in the industrialized countries, the cases continue to increase. MPM is a lethal cancer, with very little survival improvements in the last years, mirroring very limited therapeutic advances. Platinum-based chemotherapy in combination with pemetrexed and surgery are the standard of care, but prognosis is still unacceptably poor with median overall survival of approximately 12 months. The genomic landscape of MPM has been widely characterized showing a low mutational burden and the impairment of tumor suppressor genes. Among them, BAP1 and BLM are present as a germline inactivation in a small subset of patients and increases predisposition to tumorigenesis. Other studies have demonstrated a high frequency of mutations in DNA repair genes. Many therapy approaches targeting these alterations have emerged and are under evaluation in the clinic. High-throughput technologies have allowed the detection of more complex molecular events, like chromotripsis and revealed different transcriptional programs for each histological subtype. Transcriptional analysis has also paved the way to the study of tumor-infiltrating cells, thus shedding lights on the crosstalk between tumor cells and the microenvironment. The tumor microenvironment of MPM is indeed crucial for the pathogenesis and outcome of this disease; it is characterized by an inflammatory response to asbestos exposure, involving a variety of chemokines and suppressive immune cells such as M2-like macrophages and regulatory T cells. Another important feature of MPM is the dysregulation of microRNA expression, being frequently linked to cancer development and drug resistance. This review will give a detailed overview of all the above mentioned features of MPM in order to improve the understanding of this disease and the development of new therapeutic strategies.

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Section: Therapeutic Implications Of Genomics and Transcriptomics Evidencessupporting

confidence: 68%

Tumor Immune Microenvironment and Genetic Alterations in Mesothelioma

et al. 2021

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“…As one of eleven subunits of complex III, UQCRC1 is a nuclear‐encoded protein localized in the inner mitochondrial membrane. Previous studies of UQCRC1 have focused mainly on its roles in various tumors, such as malignant pleural mesothelioma and pancreatic ductal adenocarcinoma, suggesting that UQCRC1 may contribute to carcinogenesis 9,10 . Notably, mitochondrial dysfunction also plays a crucial role in the pathogenesis of PD 4,11 .…”

Section: Chromosomal Position Accession Number Variant Number Of Carrmentioning

confidence: 99%

The lack of association between ubiquinol‐cytochrome c reductase core protein I (UQCRC1) variants and Parkinson's disease in an eastern Chinese population

et al. 2020

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“…UQCRC1 serves a fundamental role in normal mitochondrial function and cellular metabolism. Mutations and abnormal expression of UQCRC1 are associated with Parkinson's disease and multiple malignancies (52)(53)(54). In pancreatic ductal adenocarcinoma, increased expression of UQCRC1 mRNA promotes cellular proliferation by generating excessive levels of ATP and OXPHOS via the ATP/RTK/AKT pathway (53).…”

Section: Discussionmentioning

confidence: 99%

Profile analysis of differentially expressed long non‑coding RNAs in metabolic memory induced by high glucose in human umbilical vein endothelial cells

et al. 2023

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Numerous long non-coding RNAs (lncRNAs) are dysregulated in the hyperglycemia-induced phenomenon of metabolic memory (MM). In the present study, the significance of these lncRNAs in MM was explored by screening for MM-involved differentially expressed lncRNAs (MMDELs) in human umbilical vein endothelial cells (HUVECs) induced by high glucose. A total of nine HUVEC samples were divided into three groups to mimic conditions of low and high glucose environments, as well as induce the state of metabolic memory. The expression of lncRNAs was profiled using RNA sequencing. Bioinformatic analysis was performed using the Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes databases to explore the parental genes from which the lncRNAs are transcribed and target genes of the MMDELs and generate enrichment datasets. Reverse transcription-quantitative PCR was performed to validate the expression levels of the selected lncRNAs. The present study identified 308 upregulated and 157 downregulated MMDELs, which were enriched in numerous physiologic processes. Key functional enrichment terms included ‘cell cycle’, ‘oocyte meiosis’ and ‘p53 signaling pathway’. In conclusion, certain MMDELs may regulate the expression level of highly associated mRNAs through various mechanisms and pathways, thereby interfering with several processes, such as the regulation of the cell cycle, and affecting vascular endothelial cell function. Furthermore, the disorders of these lncRNAs can be retained in MM, further investigation into the functions of these lncRNAs may result in novel insights and treatments, which could help control MM in patients with diabetes.

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Genomic analysis in short- and long-term patients with malignant pleura mesothelioma treated with palliative chemotherapy

Cited by 6 publications

References 24 publications

Tumor Immune Microenvironment and Genetic Alterations in Mesothelioma

Tumor Immune Microenvironment and Genetic Alterations in Mesothelioma

The lack of association between ubiquinol‐cytochrome c reductase core protein I (UQCRC1) variants and Parkinson's disease in an eastern Chinese population

Profile analysis of differentially expressed long non‑coding RNAs in metabolic memory induced by high glucose in human umbilical vein endothelial cells

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