Monopolar Spindle 1 Kinase (MPS1/TTK) mRNA Expression is Associated with Earlier Development of Clinical Symptoms, Tumor Aggressiveness and Survival of Glioma Patients

Keßler, Almuth F.; Schmitt, Dominik; Feldheim, Jonas; Monoranu, Camelia; Ernestus, Ralf‐Ingo; Löhr, Mario; Hagemann, Carsten

doi:10.3390/biomedicines8070192

Cited by 9 publications

(5 citation statements)

References 41 publications

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“…Our data clearly demonstrated that TXNDC5 was enriched in the tumor area of hyperplastic blood vessels and microvascular proliferation (Figure 4G,H ) which are known to contain highly proliferative cells and play a crucial role in tumor progression. 38 , 39 …”

Section: Resultsmentioning

confidence: 99%

Identification of thioredoxin domain containing family members' expression pattern and prognostic value in diffuse gliomas via in silico analysis

Kocatürk

2022

Cancer Medicine

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Background Gliomas are the most prevalent primary tumors of the central nervous system. Their aggressive nature and the obstacles arising during therapy highlights the importance of finding new prognostic markers and therapy targets for gliomas. TXNDC genes are members of the thioredoxin superfamily and were shown to play a role in redox homeostasis, protein folding, electron transfer and also acting as cellular adapters. The well known contribution of these processes in cancer progression prompted us to investigate if TXNDC family members may also play a role in carcinogenesis, in particular diffuse gliomas. Methods The present study used in silico analysis tools GEPIA, UCSC Xena, Gliovis, cBioPortal, and Ivy GAP to evaluate the expression pattern, prognostic value and clinical significance of TXNDC family members in diffuse gliomas. Results Our analysis showed that TXNDC family members' expression pattern differ between tumors and healthy tissues and among tumors with different grades. The detailed analysis of TXNDC5 in glioma pathogenesis revealed that TXNDC5 expression is associated with more aggressive clinical and molecular features and poor therapy success both in LGG and GBM samples. Kaplan–Meier survival curves represented a worse prognosis for patients with leveated TXNDC5 levels in LGG and all grade glioma patients. The levels of TXNDC5 was shown to be possibly regulated by hypoxia‐ER stress axis and a potential mechanism for TXNDC5‐driven glioma progression was found to be extracellular matrix (ECM) production which is known to promote tumor aggressiveness. Conclusions Our results uncovered the previously unknown role of TXNDC family members in glioma pathogenesis and showed that TXNDC5 levels could serve as a predictor of clinical outcome and therapy success and may very well be used for targeted therapy.

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Section: Resultsmentioning

confidence: 99%

Identification of thioredoxin domain containing family members' expression pattern and prognostic value in diffuse gliomas via in silico analysis

Kocatürk

2022

Cancer Medicine

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“…Expression ratio comparisons were performed using Chi-square tests, and protein expression correlation analyses were performed using Spearman's rank correlations. A P < 0.05 value indicated statistical significance [ 22 , 23 ].…”

Section: Methodsmentioning

confidence: 99%

A‐Kinase Anchor Protein 95 Is Involved in ERK1/2–Elk‐1 Signal Transduction in Colon Cancer

Kong

et al. 2023

Analytical Cellular Pathology

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Objectives. To assess A-kinase anchor protein 95 (AKAP95), B-Raf, extracellular regulated protein kinases 1/2 (ERK1/2), and Elk-1 expression in colon cancer tissue, and characterize AKAP95 associations with B-Raf, ERK1/2, Elk-1, and colon cancer clinicopathological indices. Methods. The immunohistochemistry streptavidin-perosidase (SP) method was used to determine protein expression levels in 64 colon cancer and 32 para-carcinoma tissue specimens. Results. (1) Positive AKAP95 expression rates in colon cancer tissue were higher when compared with para-carcinoma tissue (92.19% vs. 59.38%, P < 0.05 ). Similar findings were determined for B-Raf (76.56% vs. 25%, P < 0.05 ), ERK1/2 (90.63% vs. 31.25%, P < 0.05 ), and Elk-1 levels (92.19% vs. 40.63%, P < 0.05 ). (2) No significant associations were identified between AKAP95, B-Raf, ERK1/2, and Elk-1 protein expression and degree of differentiation, histological type, and lymph node metastasis in colon cancer samples ( P > 0.05 ); however, in The Cancer Genome Atlas and Gene Expression Omnibus datasets, AKAP95 was closely related to immune infiltration, and highly expressed AKAP95 was negatively associated with overall survival and relapse free survival rates in colon cancer patients. (3) Correlations were observed between AKAP95 and ERK1/2, AKAP95 and Elk-1, B-Raf and ERK1/2, B-Raf and Elk-1, and ERK1/2 and Elk-1 (all P < 0.05 ), but no correlation was observed between AKAP95 and B-Raf ( P > 0.05 ). Conclusions. AKAP95 may affect immune infiltration levels in colon cancer by participating in ERK1/2–Elk-1 signal transduction.

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“…Mps1 is an attractive oncology target because of its high expression level in cancer cells and the correlation between its expression level and the histological grade of the cancer. Based on the kinase profile, the compounds selectively inhibit MPS1 and reduce the phosphorylation of MPS1 and Phospho-HH3 signaling, successfully [ 64 , 65 ].…”

Section: Pyridopyrimidines: Therapeutic Potential and Synthesismentioning

confidence: 99%

Review on the Synthesis and Therapeutic Potential of Pyrido[2,3-d], [3,2-d], [3,4-d] and [4,3-d]pyrimidine Derivatives

2022

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The objective of this review is to list the structures composed of a pyridopyrimidine moiety which have shown a therapeutic interest or have already been approved for use as therapeutics. We consider all the synthetic protocols to prepare these pyridopyrimidine derivatives. The review is organized into four sections, successively pyrido[2,3-d]pyrimidines, pyrido[3,4-d]pyrimidines, pyrido[4,3-d]pyrimidines and pyrido[3,2-d]pyrimidines. For each compound we present the biological activity and the synthetic route reported. To produce this manuscript, the bibliographic research was done using Reaxys and Scifinder for each kind of pyridopyrimidine.

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Monopolar Spindle 1 Kinase (MPS1/TTK) mRNA Expression is Associated with Earlier Development of Clinical Symptoms, Tumor Aggressiveness and Survival of Glioma Patients

Cited by 9 publications

References 41 publications

Identification of thioredoxin domain containing family members' expression pattern and prognostic value in diffuse gliomas via in silico analysis

Identification of thioredoxin domain containing family members' expression pattern and prognostic value in diffuse gliomas via in silico analysis

A‐Kinase Anchor Protein 95 Is Involved in ERK1/2–Elk‐1 Signal Transduction in Colon Cancer

Review on the Synthesis and Therapeutic Potential of Pyrido[2,3-d], [3,2-d], [3,4-d] and [4,3-d]pyrimidine Derivatives

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