Overexpression of heat shock protein HSP90AA1 and translocase of the outer mitochondrial membrane TOM34 in HCV-induced hepatocellular carcinoma: A pilot study

Toraih, Eman A.; Alrefai, Hani; Hussein, Mohammad; Helal, Ghada M.; Khashana, Moataz S; Fawzy, Manal S.

doi:10.1016/j.clinbiochem.2018.12.001

Cited by 27 publications

(16 citation statements)

References 38 publications

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“…For reverse transcription (RT) reaction, High-Capacity cDNA Reverse Transcription Kit (P/N 4368814, Thermo Fisher Scientific, Waltham, MA, USA) was used. Extracted RNA (10 ng) was added to "2 × RT reaction mix (10 µL) containing 10 × RT Buffer (2 µL), 25 × dNTP Mix (100 mM; 0.8 µL), 10 × RT random primers (2 µL), MultiScribe™ Reverse Transcriptase enzyme (1 µL), RNase inhibitor (1 µL), and nuclease-free water (3.2 µL)", with the application of appropriate negative controls in each run, The PCR reaction subjected to 25 °C for 10 min, followed by 37 °C for 120 min, and finally 85 °C for 5 min, then hold at 4 °C in a Master cycler Gradient Thermocycler (Eppendorf, Hamburg, Germany) 44 .…”

Section: Methodsmentioning

confidence: 99%

MYD88, NFKB1, and IL6 transcripts overexpression are associated with poor outcomes and short survival in neonatal sepsis

AbdAllah

Toraih

Ageeli

et al. 2021

Sci Rep

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Toll-like receptor (TLR) family signature has been implicated in sepsis etiopathology. We aimed to evaluate the genetic profile of TLR pathway-related key genes; the myeloid differentiation protein 88 (MYD88), IL1 receptor-associated kinase 1 (IRAK1), the nuclear factor kappa-B1 (NFKB1), and interleukin 6 (IL6) in the blood of neonates with sepsis at the time of admission and post-treatment for the available paired-samples. This case–control study included 124 infants with sepsis admitted to the neonatal intensive care unit and 17 controls. The relative gene expressions were quantified by TaqMan Real-Time qPCR and correlated to the clinic-laboratory data. MYD88, NFKB1, and IL6 relative expressions were significantly higher in sepsis cases than controls. Higher levels of MYD88 and IL6 were found in male neonates and contributed to the sex-based separation of the cases by the principal component analysis. ROC analysis revealed MYD88 and NFKB1 transcripts to be good biomarkers for sepsis. Furthermore, patients with high circulatory MYD88 levels were associated with poor survival, as revealed by Kaplan–Meier curves analysis. MYD88, NFKB1, and IL6 transcripts showed association with different poor-outcome manifestations. Clustering analysis split the patient cohort into three distinct groups according to their transcriptomic signature and CRP levels. In conclusion, the study TLR pathway-related transcripts have a gender-specific signature, diagnostic, and prognostic clinical utility in neonatal sepsis.

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Section: Methodsmentioning

confidence: 99%

MYD88, NFKB1, and IL6 transcripts overexpression are associated with poor outcomes and short survival in neonatal sepsis

AbdAllah

Toraih

Ageeli

et al. 2021

Sci Rep

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“…Preliminary evidence suggests that the anticancer effects of sorafenib in HCC patients are related to these mechanisms. e results of previous studies have confirmed that SLC41A3, SEC61A1, LRP4, PPM1G, and HSP90AA1 play important roles in cancer progression [28][29][30][31][32][33][34][35][36][37][38][39]. SLC41A3 is a member of solute carrier family 41 and is involved in many cellular processes.…”

Section: Discussionmentioning

confidence: 77%

A Risk Model Based on Sorafenib-Response Target Genes Predicts the Prognosis of Patients with HCC

Liu

Zeng

et al. 2022

Journal of Oncology

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Sorafenib is used to treat digestive system tumors in patients who do not respond to or cannot tolerate surgery. However, the roles and inhibitory mechanisms of sorafenib against hepatocellular carcinoma (HCC) are unclear. Differentially expressed genes in tissues from responders and nonresponders to sorafenib were investigated using the HCC GSE109211 data set. Biological functions and mechanisms were studied using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. The expression levels of differential expressed target genes were identified in HCC tissues, using The Cancer Genome Atlas database, and their prognostic and diagnostic values were explored using survival and receiver operating characteristic curve analysis. A nomogram and risk model of sorafenib-response target genes enabled the evaluation of the prognosis of patients with HCC. The relationship between risk scores and levels of infiltrating immune cells was visualized via correlation analysis. We identified 1620 sorafenib-response target genes involved in the PPAR signaling pathway, antigen processing and presentation, and ferroptosis. SLC41A3, SEC61A1, LRP4, PPM1G, and HSP90AA1 were independent risk factors for a poor prognosis for patients with HCC and had diagnostic value. A risk model based on SLC41A3, SEC61A1, LRP4, PPM1G, and HSP90AA1 expression showed that patients with HCC in the high-risk group had a worse prognosis. Consensus-clustering analysis (performed with K set to 2) distinguished two clusters (the cluster 1 and cluster 2 groups). Patients in cluster 1 survived significantly longer than those in cluster 2. The risk score correlated with the levels of T cells, cytotoxic lymphocytes, CD8+ T cells, macrophages, memory B cells, follicular helper T cells, and other immune cells. The high risk based on the sorafenib-response targets SLC41A3, SEC61A1, LRP4, PPM1G, and HSP90AA1 represented the poor prognosis for patients with HCC and significantly correlated with the levels of immune infiltrating cells in HCC.

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“…Tomm34, a co-chaperone of Hsp70 and Hsp90, contains two TPR domains, N-terminal TPR1 and C-terminal TPR2 which binds to the highly conserved EEVD-COOH motif present in the C-terminal domain of Hsp70/Hsp90 [ 13 , 14 , 26 , 27 ]. As increased chaperone activities are a universal feature of cancer [ 28 ], Hsp70-Tomm34-Hsp90 has been confirmed to be upregulated in a variety of cancers, including liver cancer [ 16 ], lung cancer [ 29 ], gastric cancer [ 30 ] and breast cancer [ 31 ], etc. Several studies have reported the immunoreactivity of Hsp70 and Hsp90 in OSCC, which were corelated with poor prognosis [ 32 – 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…Tomm34 can interact with Hsp70 and Hsp90 to form Hsp70-Tomm34-Hsp90 complex, which acts as a co-chaperon of Hsp70 and Hsp90 to regulate its function [ 13 , 14 ]. Recent studies showed high levels of Tomm34 expressed in colorectal cancer [ 15 ], hepatocellular carcinoma [ 16 ], bladder cancer [ 17 ], breast cancer [ 18 , 19 ] epithelial ovarian cancer [ 20 ] and colon cancer [ 21 ] compared to their normal tissue counterparts. However, the expression of Tomm34 in oral squamous cell carcinoma primary tumor has not been reported and its role in OSCC is still unclear.…”

Section: Introductionmentioning

confidence: 99%

High Expression of Tomm34 and Its Correlations With Clinicopathology in Oral Squamous Cell Carcinoma

Cai

Tan

Huang

et al. 2021

Pathol. Oncol. Res.

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Tomm34, as a member of the outer mitochondrial membrane proteins, is evenly distributed between the cytoplasm and the outer mitochondrial membrane. It is up-regulated in a variety of tumors and correlates with poor prognosis. This study aimed to investigate expression of Tomm34 and its correlations with clinicopathology in oral squamous cell carcinoma (OSCC). Oncomine database and UALCAN database were utilized to predict the expression and prognosis values of Tomm34 in head and neck squamous cell carcinoma (HNSCC). By immunohistochemistry, a retrospective study was performed to verify the bioinformatics results to evaluate the Tomm34 expression and clinicopathological variables in both HPV-positive OSCC and HPV-negative OSCC. Immunohistochemistry of our cohort revealed that 48 cases fulfilled the Tomm34 high expression judgment criteria, and the overall positive rate was 60% (48/80), and 27 cases fulfilled the p16 expression judgment criteria (33.75%, 27/80). The high expression of Tomm34 was closely related with the TNM classification of OSCC (p < 0.01) and tumor size (p < 0.01) both in HPV-negative OSCC and HPV-positive OSCC, while related with lymph node metastasis (p = 0.001) in HPV-negative OSCC and drinking history (p = 0.044) in HPV-positive OSCC. In addition, the Kaplan-Meier curves indicated that higher level of Tomm34 was correlated with poorer overall survival (OS) and disease-free survival (DFS) in HPV-negative OSCC (OS, p = 0.046; DFS, p = 0.020) but not in HPV-positive OSCC (OS, p = 0.824; DFS, p = 0.782). In conclusion, Tomm34 is highly expressed in OSCC and may be a useful factor to provide prognostic information, especially in HPV-negative OSCC group.

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Overexpression of heat shock protein HSP90AA1 and translocase of the outer mitochondrial membrane TOM34 in HCV-induced hepatocellular carcinoma: A pilot study

Cited by 27 publications

References 38 publications

MYD88, NFKB1, and IL6 transcripts overexpression are associated with poor outcomes and short survival in neonatal sepsis

MYD88, NFKB1, and IL6 transcripts overexpression are associated with poor outcomes and short survival in neonatal sepsis

A Risk Model Based on Sorafenib-Response Target Genes Predicts the Prognosis of Patients with HCC

High Expression of Tomm34 and Its Correlations With Clinicopathology in Oral Squamous Cell Carcinoma

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