Increased serum mitochondrial creatine kinase activity as a risk for hepatocarcinogenesis in chronic hepatitis C patients

Enooku, Kenichiro; Nakagawa, Hayato; Soroida, Yoko; Ohkawa, Ryunosuke; Kageyama, Yuko; Uranbileg, Baasanjav; Watanabe, Naoko; Tateishi, Ryosuke; Yoshida, Haruhiko; Koike, Kazuhiko; Yatomi, Yutaka; Ikeda, Hitoshi

doi:10.1002/ijc.28720

Cited by 7 publications

(6 citation statements)

References 47 publications

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“…Both genes are effective modulators of ATP synthase-coupled respiration and belongs to mitochondrial creatine kinases (MtCK), which were found to be implicated in several tumors with poor prognosis. [ 31 32 33 34 ] Overexpressed MtCK may be part of a metabolic adaptation of cancer cells and could sustain high energy turnover, but would be also protective against stress situations like hypoxia and possibly protect cells from apoptosis. [ 35 ] Although endometriosis is a benign disease, it exhibits malignant-like biological behaviors, including adhesion, aggression, and angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Identification of Circular RNAs as a Novel Biomarker for Ovarian Endometriosis

Jia

Dai

et al. 2018

Chinese Medical Journal

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Background:Endometriosis is a challenging disease with symptoms such as dysmenorrhea and infertility. However, its etiology is still vague and there is still no effective markers or treatment. This study aimed to profile the circular RNAs (circRNAs) expressed in eutopic endometrium from patients with ovarian endometriosis and explore potential clues to the pathogenesis of endometriosis, providing an evidence for clinical diagnosis and treatment.Methods:A total of 63 clinical samples, including control endometrium (n = 22) and eutopic endometrium (n = 41), were collected from Peking Union Medical College Hospital between May 1, 2016, and December 31, 2016. Of them, four samples in each group were used for circRNA microarray. Then, four upregulated circRNAs were screened out for quantitative real-time polymerase chain reaction (qRT-PCR) validation. After that, bioinformatics analysis was performed to predict miRNAs targeted by validated circRNAs and investigate the circRNA-miRNA-mRNA interactions.Results:Among 88 differentially expressed circRNAs, 11 were upregulated and 77 were downregulated in eutopic endometrium of patients with endometriosis. qRT-PCR validation results for two upregulated circRNAs (circ_0004712 and circ_0002198) matched the microarray results. The area under the receiver operating characteristic curve of circ_0002198 for distinguishing ovarian endometriosis was 0.846 (95% confidence interval [CI]: 0.752–0.939; P < 0.001) while that of circ_0004712 was 0.704 (95% CI: 0.571–0.837; P = 0.008). On the basis of target prediction, we depicted the molecular interactions between the identified circRNAs and their dominant target miRNAs, as well as constructed a circRNA-miRNA-mRNA network.Conclusions:This study provides evidence that circRNAs are differentially expressed between eutopic and normal endometrium, which suggests that circRNAs are candidate factors in the activation of endometriosis. circ_0002198 and circ_0004712 may be potential novel biomarkers for the diagnosis of ovarian endometriosis.

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Section: Discussionmentioning

confidence: 99%

Identification of Circular RNAs as a Novel Biomarker for Ovarian Endometriosis

Jia

Dai

et al. 2018

Chinese Medical Journal

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“…It was also observed that patients with liver cancer had significant reduced survival time prior to cancer-related treatment, suggesting that high expression of mitochondrial CK could be associated with a poor prognosis in hepatocellular carcinoma (Uranbileg et al, 2014). Besides, it was indicated that increase of mitochondrial CK activity denoted a cumulating risk for hepatocarcinogenesis in patients who had chronic hepatitis C (Enooku et al, 2014). There was one recent study indicating that overexpression of mitochondrial CK was markedly associated with shorter progression-free and overall survival times in patients with breast cancer (Qian et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Creatine Kinase (CK)-MB-to-Total-CK Ratio: a Laboratory Indicator for Primary Cancer Screening

Chang¹,

Liou²,

Su³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: For the determination of creatine kinase (CK)-MB, the immunoinhibition method is utilized most commonly. However, the estimated CK-MB activity may be influenced by the presence of CK isoenzymes in some conditions like cancer. Thus, a CK-MB-to-total-CK ratio more than 1.0 could be found in such a situation. The study aimed to explore the relationship of cancer to high CK-MB-to-total-CK ratio. Materials and Methods: From January 2011 to December 2014, laboratory data on all CK-MB and total CK test requests were extracted at Far Eastern Memorial Hospital (88,415 requests). Patients with a CK-MB-to-total-CK ratio more than 1.0 were registered in this study. Clinical data including tumor location, tumor TNM stage and metastatic status were also collected. Results: A total of 846 patients were identified with a CK-MB-to-total-CK ratio more than 1.0. Of these, 339 (40.1%) were diagnosed with malignancies. The mean CK-MB-to-total-CK ratio was significantly higher in malignancy than in non-malignancy (1.35±0.28 vs 1.25±0.23, p<0.001) groups. The most frequent malignancy with a CK-MB-to-total-CK ratio more than 1.0 was colorectal cancer (1.42±0.28, 16.5%, n=56), followed by lung cancer (1.38±0.24, 15.9%, n=54) and hepatocellular carcinoma (14.5%, n=49). Higher CK-MB-to-total-CK ratios in hematological malignancies (1.44±0.41)were also noted. Additionally, the CK-MB-to-total-CK ratio was markedly higher in advanced stage malignancy than in early stage (1.37±0.26 vs. 1.29±0.31, p=0.014) and significantly higher in liver metastasis than in non-liver metastasis (1.48±0.30 vs. 1.30±0.21, p<0.001). Conclusions: The CK-MB-to-total-CK ratio is an easily available indicator and could be clinically utilized as a primary screening tool for cancer. Higher ratio of CK-MB-to-total-CK was specifically associated with certain malignancies, like colorectal cancer, lung cancer and hepatocellular carcinoma, as well as some cancer-associated status factors such as advanced stage and liver metastasis.

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“…3,48 Furthermore, there were indications that MtCK showed a cumulating risk for hepatocarcinogenesis in chronic hepatitis C patients. 49 There are also indications that overexpression of MtCK was linked to shorter overall survival time in breast cancer patients. 46,50 Amamoto et al suggest that uMtCK is downregulated with prostate cancer progression.…”

Section: Using Mtck As a Marker For Detection Of Cancersmentioning

confidence: 99%

“…Serum AFP levels and serum MtCK activity also showed a significant correlation. 49 Enooku et al also suggested that based on experiments on mice treated with bile duct ligation for four weeks, uMtCK mRNA levels in the liver were significantly increased compared to sham-operated mice. These results suggest that uMtCK expression, especially in hepatocytes, may increase in the fibrotic liver and potentially lead to increased serum MtCK activity.…”

Section: Mtck In Hepatitis C and Liver Fibrosis Stagingmentioning

confidence: 99%

“…In conclusion, the higher serum MtCK activity in chronic hepatitis C patients may be an independent risk for HCC development. 49 In general, healthy liver tissue does not express detectable levels of uMtCK and therefore could be a sign of pathological development; evidence from CK gene transgenic mice showed that CK expression in the liver could lead to inhibition of apoptosis and protect against hypoxia or endotoxin perfusion and thus play a protective role in injured liver tissue. 49 A review of the behavior of MtCK in relation to the conditions discussed can be found in Table 3.…”

Section: Mtck In Hepatitis C and Liver Fibrosis Stagingmentioning

confidence: 99%

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The role and behaviour of mitochondrial creatine kinase in hepatocellular carcinoma and its potential use as a tumor detecting biomarker for cancer patients

et al. 2023

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Hepatocellular carcinoma (HCC) is responsible for approximately 75% of all liver cancer cases, which is the seventh most prevalent cancer and the second most common cause of cancer mortality worldwide. The prognosis of HCC depends on its stage and the severity of liver disease at the time of diagnosis, but there are still problems in detecting and treating HCC patients on time and effectively. Being unable to diagnose HCC patients at an early stage and ineffective therapies for HCC patients with advanced stages are associated with the disease's high mortality. Liver transplantation could be a treatment option If patients are diagnosed early, but unfortunately, most patients are diagnosed at an advanced stage where chemotherapy is necessary. Thus, an effective strategy for early detection of HCC is necessary since there was no effective chemotherapy for advanced HCC for a long time, and therapies such as the anti-angiogenesis pathway can only extend the median survival from 7.9 months to 10.7 months which is a step forward but not enough. In this article, we review the role of MtCK in HCC and its potential use as a marker to see if using it can be beneficial to patients.

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Increased serum mitochondrial creatine kinase activity as a risk for hepatocarcinogenesis in chronic hepatitis C patients

Cited by 7 publications

References 47 publications

Identification of Circular RNAs as a Novel Biomarker for Ovarian Endometriosis

Identification of Circular RNAs as a Novel Biomarker for Ovarian Endometriosis

Creatine Kinase (CK)-MB-to-Total-CK Ratio: a Laboratory Indicator for Primary Cancer Screening

The role and behaviour of mitochondrial creatine kinase in hepatocellular carcinoma and its potential use as a tumor detecting biomarker for cancer patients

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