Identification of important invasion and proliferation related genes in adrenocortical carcinoma

Alshabi, Ali Mohamed; Vastrad, Basavaraj; Shaikh, Ibrahim Ahmed; Vastrad, Chanabasayya

doi:10.1007/s12032-019-1296-7

Cited by 23 publications

(40 citation statements)

References 232 publications

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“…TK1 was found to be linked to both poor overall patient survival and increased expression in stage 4 ACC patients, which indicate TK1 correlations to tumor progression (20). Among the DEGs identified by Song et al in PCa patients, TK1 was shown to contribute to PCa pathogenesis, increasing with stage 4 tumors (19,20).…”

Section: Introductionmentioning

confidence: 91%

“…The RNA-seq data was analyzed using the TIMER program developed by Li et al Correlation strength and p value for negative and positive correlations between TK1 and invasion factors are shown for significant correlations (p ≤.05). Despite no observable strong pattern between TK1 and positive or negative correlations, we decided to evaluate TK1 affects in vitro on cellular invasion based on findings from others previous research (18)(19)(20) . Using Xcelligence technology, we measured the effect of TK1 on cellular invasion over a 24-hour period.…”

Section: Effects Of Tk1 On Cellular Invasionmentioning

confidence: 99%

“…Increased expression of the TK1 enzyme is associated with cancer aggressiveness and TK1 serum levels progressively increase with cancer grade (T1-T4) in breast tissue (14,17).. The role of TK1 and its impact on tumor progression has recently been evaluated in protein networks (18)(19)(20). In one study, TK1 was evaluated in invasive MDA-MB-231 cells within a protein network that included HSP90AB1, CSNK2B, YWHAB and VIM (18).…”

Section: Introductionmentioning

confidence: 99%

“…Knockdowns of the complete network inhibited cellular invasion during the epithelial-mesenchymal transition when compared to non-invasive MCF7 and non-tumoral MCF-10A cell lines (18). Other studies have bioinformatically associated TK1 with additional protein networks that contribute to tumor progression in adrenocortical carcinoma (ACC) and prostate cancer (PCa) (19,20). Alshabi et.…”

Section: Introductionmentioning

confidence: 99%

“…al, identified through differentially expressed genes (DEGs) and protein-protein interaction networks in ACC patients that of all the affected pathways, pyrimidine deoxyribonucleoside salvage and cell cycle were some of the most enriched pathways (20). TK1 was found to be linked to both poor overall patient survival and increased expression in stage 4 ACC patients, which indicate TK1 correlations to tumor progression (20). Among the DEGs identified by Song et al in PCa patients, TK1 was shown to contribute to PCa pathogenesis, increasing with stage 4 tumors (19,20).…”

Section: Introductionmentioning

confidence: 99%

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TK1 in Cancer Progression: elucidating its influence on cellular invasion and survival

Bitter

Townsend

Tsai

et al. 2019

Preprint

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1. Background: The salvage pathway enzyme thymidine kinase 1 (TK1) is elevated in the serum of several different cancer types and higher expression is associated with more aggressive tumor grade. As a result, it has potential as a biomarker for diagnosis and prognosis. Recent studies indicate that TK1 may be involved in cancer pathogenesis; however, its direct involvement has not been identified. We propose to evaluate the effects of TK1 on cancer progression in vitro through measuring cellular invasion and survival of breast cancer cells.2.Methods: Breast cancer cells MDA-MB-231, HCC 1806, and MCF7 were cultured according to standard techniques. We employed the use of TK1 target siRNA and a CRISPR-Cas9 TK1 knockout plasmid to compare transfected cell lines to wild type cell lines. Protein factors in survival and invasive pathways were also tested for correlations to TK1 in BRCA RNA-seq patient data (n=1095) using the TIMER program. Cellular invasion was quantified in cell index (factor of impedance) over a 24-hour period. Cell survival was measured by apoptosis under metabolic and DNA stress using flow cytometry. All results were statistically assessed using an ANOVA or t-test in GraphPad PRISM®.3.Results: Cellular invasion assays assessing wild type and TK1 knockdown/knockout (TK1-/-) cell types showed TK1-/- cell lines had increased invasion potential (p= 0.0001). Bioinformatically, we saw a strong overall negative correlation between apoptotic factors and TK1 (p ≤ 0.05). When testing TK1 effects on cell survival we saw a protective affect under DNA stress (p ≤ 0.05), but not under metabolic stress (p= 0.0001).4.Conclusion From cell cycle analysis, we observed a shift towards S phase in TK1-/- cells. This shift to S phase would promote growth and account for the increased cellular invasion and decrease in metabolic induced stress in TK1-/- cells. We propose that cancer cells still may elicit a cancer progressive phenotype based on effects of TK1, but that a system which isolates TK1 is not effective to understand the effects. Instead, identifying protein networks inclusive of TK1 will help to elucidate its effects on cancer progression.

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Section: Introductionmentioning

confidence: 91%

Section: Effects Of Tk1 On Cellular Invasionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

TK1 in Cancer Progression: elucidating its influence on cellular invasion and survival

Bitter

Townsend

Tsai

et al. 2019

Preprint

View full text Add to dashboard Cite

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Mutational signatures and their association with cancer survival and gene expression in multiple cancer types

Karihtala,

Kilpivaara,

Porvari

2024

Intl Journal of Cancer

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Different endogenous and exogenous mutational processes cause specific patterns of somatic mutations and mutational signatures. Although their biological research has been intensive, there are only rare studies assessing the possible prognostic role of mutational signatures. We used data from The Cancer Genome Atlas to study the associations between the activity of the mutational signatures and four survival endpoints in 18 types of malignancies. We further explored the prognostic differences according to, for example, the HPV status in head and neck squamous cell carcinomas and smoking status in lung cancers. The predictive power of the signatures over time was evaluated with a dynamic area under the curve model, and the links between mutational signature activities and differences in gene expression patterns were analyzed. In 12 of 18 studied cancer types, we identified at least one mutational signature whose activity predicted survival outcomes after adjusting for the established prognostic factors. For example, overall survival was associated with the activity of mutational signatures in nine cancer types and disease‐specific survival in seven cancer types. The clock‐like signatures SBS5 and SBS40 were most commonly associated with survival endpoints. The genes of the myosin binding protein and melanoma antigen families were among the most substantially dysregulated genes between the signatures of low and high activity. The differences in gene expression also revealed various enriched pathways. Based on these data, specific mutational signatures associate with the gene expression and have the potential to serve as strong prognostic factors in several cancer types.

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Serum and urine metabolomics analyses reveal metabolic pathways and biomarkers in relation to nasopharyngeal carcinoma

Liao

Zhong

et al. 2023

Rapid Comm Mass Spectrometry

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Rationale: Nasopharyngeal carcinoma (NPC) is a malignant tumor that is endemic in Southeast Asia, North Africa, and southern China. There is an urgent need for effective early diagnosis and treatment of this disease since NPC is currently often detected at advanced stages. Methods: To reveal the underlying metabolic mechanisms and discover potential diagnostic biomarkers of NPC, we employed ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) and UHPLC-Q-Exactive Orbitrap MS, respectively, to analyze 54 serum samples and 54 urine samples from 27 patients with NPC and 27 healthy control individuals. Results: A total of 1230 metabolites were determined in serum samples, and 181 of the 1230 metabolites were significantly changed in NPC patients. The 181 metabolites were enriched in 16 pathways, including biosynthesis of unsaturated fatty acids, cholesterol metabolism, and ferroptosis. A total of 2509 metabolites were detected in the urine samples. Among them, 179 metabolites were significantly altered in NPC patients, and these metabolites were enriched in eight pathways, including the tricarboxylic acid (TCA) cycle and caffeine metabolism. Seven metabolites, including creatinine and paraxanthine, were found to be significantly changed in both NPC serum and urine samples. Based on them, further biomarker analysis revealed that the panel of three serum metabolites, octanoylcarnitine, creatinine, and decanoyl-l-carnitine, displayed a perfect diagnostic performance (area under the curve [AUC] = 0.973) to distinguish NPC patients from controls, while the other three-metabolite biomarker panel, consisting of stachydrine, decanoyl-lcarnitine, and paraxanthine, had an AUC = 0.809 to distinguish NPC and control in urine samples. Conclusion: This work highlights the key metabolites and metabolic pathways disturbed in NPC and presents potential biomarkers for effective diagnosis of this disease.

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Identification of important invasion and proliferation related genes in adrenocortical carcinoma

Cited by 23 publications

References 232 publications

TK1 in Cancer Progression: elucidating its influence on cellular invasion and survival

TK1 in Cancer Progression: elucidating its influence on cellular invasion and survival

Mutational signatures and their association with cancer survival and gene expression in multiple cancer types

Serum and urine metabolomics analyses reveal metabolic pathways and biomarkers in relation to nasopharyngeal carcinoma

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