Clinical implications of proliferation activity in T1 or T2 male gastric cancer patients

Kim, Young Woo; Eom, Bang Wool; Kook, Myeong Cherl; Kim, Han Seong; Kim, Mi Kyung; Hwang, Hai Li; Chandra, Vishal; Poojan, Shiv; Song, Yura; Koh, Jae Soo; Bae, Chang Jun; Ro, Jungsil; Hong, Kyung Taek

doi:10.1038/emm.2015.79

Cited by 7 publications

(6 citation statements)

References 27 publications

(34 reference statements)

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“…The relationship between these genes and prognosis in OC is poorly studied. upregulation of chromatin CKAP2 is an independent prognostic marker for shorter relapse-free survival in early-stage breast cancer (25), and for significantly worse prognoses in male patients with T1-2 gastric cancer (26). Downregulation of CLDN10 indicates shorter OS in some patients with lung adenocarcinoma (27).…”

Section: Discussionmentioning

confidence: 99%

Cross-validation of genes potentially associated with overall survival and drug resistance in ovarian cancer

Gao

Liu

et al. 2017

Oncology Reports

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Ovarian cancer is the leading cause of death among malignancies of the female reproductive system. The 5-year survival rates of ovarian cancer (OC) patients are very poor as a result of recurrent disease and emergence of drug resistance; thus, studies to find predictive markers and factors for drug resistance are ongoing. In the present study, based on the microarrays from The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO) profiles covering 1648 OC patients, 11 out of 136 genes that were found to be significantly dysregulated in OC were associated with overall survival (OS) in 489 OC patients of the TCGA cohort. Of these genes, CRISP3, LYVE1, OVGP1 and BCHE were identified as independent prognostic factors, with decreased expression of the first three genes predicting shorter OS, and decreased BCHE predicting longer OS. OVGP1, BCHE and further two genes, CKAP2 and CLDN10, were consistently and remarkably associated with OS when the number of patients increased from 489 to 1583, with increased CKAP2 and decreased CLDN10 predicted shorter OS; combining the four genes provided better predictions. Associations among the four genes with OS in subgroups of OC were further verified. Downregulation of OVGP1 was significantly associated with shorter OS in all subgroups of OC patients, including subgroups of 752 patients treated with chemotherapy regimens containing taxol, 763 with both platin and taxol, 1364 with platin, 371 patients with grade 1-2 disease, 968 with grade 3 disease, 1148 with stage III-IV disease, and 439 with TP53 mutations. In addition, CKAP2 expression was significantly associated with shorter OS in 515 OC patients who had low CA125 levels. Furthermore, comprehensive analyses that including RT-qPCR, bioinformatics analysis and clinical data revealed an association of CKAP2, BCHE, CLDN10 and OVGP1 with drug resistance in OC. The genes identified in the present study might be prognostic factors as well as potential therapeutic targets in the treatment of OC.

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Section: Discussionmentioning

confidence: 99%

Cross-validation of genes potentially associated with overall survival and drug resistance in ovarian cancer

Gao

Liu

et al. 2017

Oncology Reports

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“…Cytoskeleton-associated protein 2 ( CKAP2 ) is an important paralog of CKAP2L that functions to stabilize microtubules and plays a key role in the regulation of cell division [ 28 , 29 ]. CKAP2 gene is also upregulated in various kinds of cancer, including breast [ 30 ], prostate [ 31 , 32 ], stomach [ 33 , 34 ], and ovarian [ 35 ] cancers, as well as glioma [ 36 ]. We therefore hypothesized that CKAP2L may play similar roles in glioma.…”

Section: Discussionmentioning

confidence: 99%

CKAP2L Knockdown Exerts Antitumor Effects by Increasing miR-4496 in Glioblastoma Cell Lines

Tsai

Chou

et al. 2020

IJMS

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Despite advances in the diagnosis and treatment of the central nervous system malignancy glioma, overall survival remains poor. Cytoskeleton-associated protein 2-like (CKAP2L), which plays key roles in neural progenitor cell division, has also been linked to poor prognosis in lung cancer. In the present study, we investigated the role of CKAP2L in glioma. From bioinformatics analyses of datasets from The Cancer Gene Atlas and the Chinese Glioma Genome Atlas, we found that CKAP2L expression correlates with tumor grade and overall survival. Gene set enrichment analysis (GSEA) showed that MITOTIC_SPINDLE, G2M_CHECKPOINT, and E2F_TARGETS are crucially enriched phenotypes associated with high CKAP2L expression. Using U87MG, U118MG, and LNZ308 human glioma cells, we confirmed that CKAP2L knockdown with siCKAP2L inhibits glioma cell proliferation, migration, invasion, and epithelial-mesenchymal transition. Interestingly, CKAP2L knockdown also induced cell cycle arrest at G2/M phase, which is consistent with the GSEA finding. Finally, we observed that CKAP2L knockdown led to significant increases in miR-4496. Treating cells with exogenous miR-4496 mimicked the effect of CKAP2L knockdown, and the effects of CKAP2L knockdown could be suppressed by miR-4496 inhibition. These findings suggest that CKAP2L is a vital regulator of miR-4496 activity and that CKAP2L is a potentially useful prognostic marker in glioma.

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“…CKAP2, also known as TMAP, serves a vital role in cell mitosis and cell death in a P53-dependent manner ( 30 ). Previous research has been performed on various human tumors, including gastric cancer, breast cancer, ovarian cancer and prostate cancer ( 15 – 21 ). Notably, CKAP2 has been reported to be overexpressed in the aforementioned cancer types and reduces the OS of patients by various mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, CKAP2 has been reported to be overexpressed in the aforementioned cancer types and reduces the OS of patients by various mechanisms. For example, gastric adenocarcinoma, which is a poorly differentiated, highly malignant adenocarcinoma, possesses a relatively high number of cytoplasmic CKAP2-positive cells ( 15 ). In addition, in ovarian cancer, the OS of patients with high levels of CKAP2 is shorter, and CKAP2, along with butyrylcholinesterase, claudin 10 and oviductal glycoprotein 1 mediates resistance to chemotherapy ( 16 ).…”

Section: Discussionmentioning

confidence: 99%

“…CKAP2 was recently reported to be a substrate of cyclin-dependent kinase (CDK)1-cyclin B and was indicated to be essential for bipolar spindle formation ( 14 ). The oncogenic nature of CKAP2 in the occurrence and development of gastric ( 15 ), ovarian ( 16 ) and breast cancer ( 17 ), and other malignant tumors ( 18 – 21 ) has been elaborated. However, limited studies have assessed the biological characteristics and significance of CKAP2 in HGG.…”

Section: Introductionmentioning

confidence: 99%

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CKAP2 expression is associated with glioma tumor growth and acts as a prognostic factor in high‑grade�glioma

Wang

Huang

et al. 2018

Oncol Rep

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Cytoskeletal-associated protein 2 (CKAP2), which is also known as tumor-associated microtubule-associated protein, has been reported to be dysregulated in various types of human cancer. However, the role of CKAP2 in glioma has not been fully elucidated. The present study evaluated the expression pattern of CKAP2 using the Chinese Glioma Genome Atlas microarray database, which included 301 patients, and validated the findings using The Cancer Genome Atlas RNA sequencing database. Kaplan-Meier survival analysis, and univariate and multivariate Cox analyses, were used to estimate survival distributions. Furthermore, the biological implication of aberrant CKAP2 expression in high-grade glioma (HGG) was investigated using Gene Ontology analysis, gene set enrichment analysis, gene set variation analysis and STRING. The results indicated that patients with HGG exhibited significantly higher CKAP2 expression levels compared with patients with low-grade glioma in both databases. Higher expression levels of CKAP2 were significantly associated with shorter overall survival and progression-free survival of patients with HGG. Furthermore, CKAP2 was also positively correlated with known malignant factors, including high Ki67 expression and phosphatase and tensin homolog mutations. The univariate and multivariate Cox regression analyses demonstrated that CKAP2 may be a novel independent prognostic biomarker for patients with HGG. Functional assays also indicated that CKAP2 was closely associated with the cell cycle, mitosis and cell proliferation. These results suggested that CKAP2 may be associated with tumor growth and could serve as an independent prognostic factor, particularly in patients with HGG.

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Clinical implications of proliferation activity in T1 or T2 male gastric cancer patients

Cited by 7 publications

References 27 publications

Cross-validation of genes potentially associated with overall survival and drug resistance in ovarian cancer

Cross-validation of genes potentially associated with overall survival and drug resistance in ovarian cancer

CKAP2L Knockdown Exerts Antitumor Effects by Increasing miR-4496 in Glioblastoma Cell Lines

CKAP2 expression is associated with glioma tumor growth and acts as a prognostic factor in high‑grade�glioma

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