Objective assessment of adrenocortical carcinoma driver genes and their correlation with tumor pyruvate kinase M2

Das, Rudradip; Chowdhury, Moumita Ghosh; Raundal, Sonal; Jadhav, Jyotika; Kumar, Navin; Patel, Sagarkumar; Shard, Amit

doi:10.1016/j.gene.2022.146354

Cited by 3 publications

(1 citation statement)

References 62 publications

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“…Furthermore, the compounds unequivocally activated tumor pyruvate kinase M2 (PKM2) in lactate dehydrogenase-coupled enzyme assay. PKM2 is a crucial regulator enzyme in glycolysis − and is upregulated in OSCC. Thus, it is a potential therapeutic avenue to expand the canvas of effective bio-organometallic anticancer agents and create an opportunity to design small molecule-based PKM2 modulators to terminate cancer growth.…”

Section: Introductionmentioning

confidence: 99%

A Series of Ferrocene-Containing Pyrazolo[1,5-a]pyrimidines Induce a Strong Antiproliferative Effect against Oral Cancer Cells

et al. 2022

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Bio-organometallic agents confer superior physicochemical profiles inaccessible to purely organic molecules. As current chemotherapeutic regimes are maligned by the toxicity and chemoresistance of cisplatin and carboplatin, the development of an arsenal of metallodrugs becomes indispensable. Metallocenes such as ferrociphenols, JAHA, and ferrocene-labeled estradiol exhibit potent anticancer profiles. Oral squamous cell carcinomas are shown to be an excellent model to assess the impact of ferrocene-based pyrazolopyrimidines (FPPs) as chemotherapeutic agents. We show here synthesis and preliminary mechanistic investigations of FPPs in the CAL 27 cell line. The results established that some of the FPPs like 4u display strong antiproliferative behavior selectively against cisplatin-resistant oral cancer cells with an IC 50 value of 7.49 μM. It was also found to activate tumor pyruvate kinase M2 (PKM2), a critical metabolic conduit in cancer. Furthermore, 4u induced apoptosis in cells and arrested cell growth in the S-phase of the cell cycle. In silico studies established that the molecule binds at the DASA-58 binding site of PKM2.

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Section: Introductionmentioning

confidence: 99%

A Series of Ferrocene-Containing Pyrazolo[1,5-a]pyrimidines Induce a Strong Antiproliferative Effect against Oral Cancer Cells

et al. 2022

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Comprehensive exploration of novel imidazopyrimidine derivatives: Design, synthesis, computational assessment, and anti-breast cancer activity

Patel,

Pulugu,

Das

et al. 2025

Journal of Molecular Structure

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Multi-omics profiling highlights karyopherin subunit alpha 2 as a promising biomarker for prognosis and immunotherapy respond in pediatric and adult adrenocortical carcinoma

Chen,

Fang,

Zhong

et al. 2024

Annals of Medicine

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Purpose Adrenocortical carcinoma (ACC) afflicts both pediatric and adult populations and is characterized by dismal prognosis and elevated mortality. Given the inconsistent therapeutic benefits and significant side effects associated with the conventional chemotherapy agent, mitotane, and the nascent stage of immunotherapy and targeted treatments, there is an urgent need to identify novel prognostic biomarkers and therapeutic targets in ACC. Methods Utilizing multi-omic datasets from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), we employed Weighted Gene Co-expression Network Analysis (WGCNA), Cox regression, Receiver Operating Characteristic (ROC) curves, and survival analyses to sift for potential prognostic biomarkers. We subsequently validated these findings through immunohistochemistry and cell assays, and delved into the biological role of KPNA2 in ACC through functional enrichment analysis, mutational landscape, and immune cell infiltration. Results A total of 77 progression-associated genes with aberrant chromosomal accessibility were discerned within the TCGA-ACC dataset. By integrating ROC and Cox regression from GEO datasets, KPNA2 emerged as an independent risk factor portending poor outcomes in ACC. ATAC-seq analysis revealed attenuated chromatin accessibility of KPNA2 in cases with unfavorable prognosis. Immunohistochemistry corroborated elevated KPNA2 expression, which was linked to enhanced proliferation and invasion. Elevated KPNA2 levels were found to activate oncogenic pathways while simultaneously suppressing immunological responses. Immune infiltration analysis further revealed a decrement in CD8+ T-cell infiltration in KPNA2-high cohorts. Conclusion This study demonstrates the clinical and biological significance of KPNA2 in ACC and suggests that KPNA2 could serve as a promising biomarker for predicting prognosis and immunotherapeutic responses in pediatric and adult ACC patients.

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Objective assessment of adrenocortical carcinoma driver genes and their correlation with tumor pyruvate kinase M2

Cited by 3 publications

References 62 publications

A Series of Ferrocene-Containing Pyrazolo[1,5-a]pyrimidines Induce a Strong Antiproliferative Effect against Oral Cancer Cells

A Series of Ferrocene-Containing Pyrazolo[1,5-a]pyrimidines Induce a Strong Antiproliferative Effect against Oral Cancer Cells

Comprehensive exploration of novel imidazopyrimidine derivatives: Design, synthesis, computational assessment, and anti-breast cancer activity

Multi-omics profiling highlights karyopherin subunit alpha 2 as a promising biomarker for prognosis and immunotherapy respond in pediatric and adult adrenocortical carcinoma

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