Serum TK1 is a more reliable marker than CEA and AFP for cancer screening in a study of 56,286 people

Wang, Yu; Jiang, Xiaoqi; Shao-liang, Dong; Shen, Jian-kun; Yu, Hao; Zhou, Ji; Li, Jin; Ma, Huili; He, Ellen; Skog, Sven

doi:10.3233/cbm-160594

Cited by 37 publications

(37 citation statements)

References 15 publications

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“…Usually, α-fetoprotein (AFP) has been used as diagnosis biomarker for screening out HCC patients for decades (Zhang et al 2004;Bai et al 2017). However, studies indicate that AFP has poor sensitivity and specificity for HCC (Akeyama et al 1972;Wang et al 2016). Thus, either doctors or researchers kept craving more efficient biomarkers for HCC.…”

Section: Discussionmentioning

confidence: 99%

Microarray Expression Profiling of microRNAs Reveals Potential Biomarkers for Hepatocellular Carcinoma

Zhu

Huang

et al. 2018

Tohoku J. Exp. Med.

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Hepatocellular carcinoma (HCC) remains a major health problem for delayed diagnosis, inefficient surveillance and poor prognosis. Recent studies have indicated that non-coding RNAs contribute to the development of new strategies for diagnosis and treatment of HCC. In the present study, we employed 18 pairs of HCC and matched non-tumor tissues for the identification of differentially expressed microRNAs (miRNAs) in HCC, among which 7 paired specimens were selected randomly for microarray detection. Totally, twenty-three miRNAs were screened out to have statistically significant differences with the threshold of P < 0.01 and fold-change ≥ 2.0 or ≤ 0.5 using miRNA microarray. In the validation stage, two miRNAs exhibited higher expression levels in the HCC tissues compared with those in the matched non-tumor tissues, whereas the expression levels of ten miRNAs were lower in the HCC tissues than those in the matched non-tumor tissues. In further analysis, eight miRNAs, including miR-4270, miR-125b-5p, miR-199a-3p, miR-10a-5p, miR-424-5p, miR-195-5p, miR-106b-5p and miR-3651, were retained, when another constraint about the signal intensity of microarray probes was established. Among these miRNAs, our study was the first to show the higher expression level of miR-3651 and the lower expression level of miR-4270 in HCC. The areas under the receiver-operating-characteristic curve values of miR-3651 and miR-4270 were 0.730 and 0.967, respectively, indicating their potential diagnostic values. Our results may help provide the context for expanded interpretations of miRNA studies involved in the progression of liver disease, potentially serving as a diagnostic tool of HCC.

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Section: Discussionmentioning

confidence: 99%

Microarray Expression Profiling of microRNAs Reveals Potential Biomarkers for Hepatocellular Carcinoma

Zhu

Huang

et al. 2018

Tohoku J. Exp. Med.

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“…Thymidine Kinase 1 (TK1) is a cell cycle regulated DNA synthesis enzyme that is up-regulated in malignant tissues during early stages of cancer development [5,6]. Multiple studies have shown that TK1 levels in serum (sTK1) and tissues correlate with cancer progression, patient outcome and recurrence events [7][8][9][10][11][12]. Although TK1 was initially proposed as a cancer biomarker for several blood cancers [13,14], it has also been shown to be a reliable biomarker for a wide variety of solid malignancies [15][16][17][18][19][20].…”

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confidence: 99%

Novel monoclonal antibodies against thymidine kinase 1 and their potential use for the immunotargeting of lung, breast and colon cancer cells

et al. 2020

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Background: Thymidine kinase 1 (TK1) is a pyrimidine salvage pathway enzyme that is up-regulated in malignant tissues and elevated in the serum of cancer patients. While TK1 has been well established as a tumor biomarker, little has been done to explore its potential as a tumor target. Recently, we reported the membrane expression of TK1 on malignant cells, but not on normal cells. This study explores the possible use of monoclonal antibodies for the targeting of membrane associated TK1 in lung, breast, colon and prostate cancer cells. Methods: We generated and evaluated a panel of monoclonal antibodies against six different epitopes exposed in the tetrameric form of TK1. Antibodies were developed with hybridoma technology and validated with Western blot, siRNA TK1 knockdown, enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The therapeutic potential of the antibodies was evaluated in vitro in antibody-dependent cell-mediated-cytotoxicity (ADCC) experiments. Results: Binding of the antibodies to TK1 was confirmed by Western blot in purified recombinant protein, cancer serum, and cell lysate. After a TK1 knockdown was performed, a reduction of TK1 expression was observed with five antibodies. Using indirect ELISA, we identified 3B2E11, 9C10, 7H2, 3B4, 8G2 among the most sensitive antibodies (LOD = 10.73-66.9 pg/ml). Surface expression of TK1 on the membrane of various cancer cell lines was analyzed with flow cytometry. Antibodies 8G2, 3B4, 7HD and 5F7G11 detected TK1 on the membrane of various cancer cell lines, including lung, prostate, colon and breast. No significant binding was detected on normal lymphocytes. Increased cytolysis of lung (~ 70%. p = 0.0001), breast (~ 70%, p = 0.0461) and colon (~ 50% p = 0.0216) cancer cells by effector cells was observed when anti-TK1 antibodies were added during ADCC experiments. Conclusions: The antibodies developed showed potential to be used to detect and target TK1 on the membrane of various tumor cells. The targeting of TK1 in malignant cells using monoclonal antibodies may be a feasible approach for the elimination of high TK1 expressing tumor cells.

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“…Studies have reported that the expression levels of miR-183 and thymidine kinase (TK) 1 (TK1) in the peripheral blood of malignant carcinoma patients were significantly increased, suggesting their potential as serological markers for cancer diagnosis [9][10][11][12]. In this study, the expression levels of serum miR-183 https://doi.org/10.1515/biol-2017-0029…”

Section: Introductionmentioning

confidence: 73%

The diagnostic value of serum microRNA-183 and TK1 as biomarkers for colorectal cancer diagnosis

Zhu¹,

Wang²,

Chen³

2017

Open Life Sciences

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ObjectiveTo evaluate the serum levels of microRNA-183 (miR-183) and thymidine kinase 1 (TK1) in colorectal cancer patients and their clinical value as biomarkers for colorectal cancer auxiliary diagnosis.MethodsForty-six pathology confirmed colorectal cancer patients and 46 healthy controls were included in this study. The serum levels of miR-183 and TK1 in colorectal cancer patients and healthy controls were examined by real-time PCR and chemiluminescence detection assay respectively. The diagnostic value of serum miR-183 and TK1 as tumor biomarkers for colorectal cancer detection was evaluated through receiver operating characteristic (ROC) curves.ResultsThe median serum relative expression of miR-183 was 1.33 (0.34-5.65) and 0.88 (0.26-4.67) in colorectal cancer patients and healthy controls respectively with significant statistical difference (p<0.05). Using serum miR-183 as the diagnostic reference, the colorectal cancer diagnosis sensitivity, specificity and AUC was 65.22%, 63.04% and 0.69 respectively. The median serum level of TK1 was 3.33 (0.78-5.78) pmol/L and 0.99 (0.34-4.46) pmol/L in colorectal cancer patients and healthy controls respectively with significant statistical difference (p<0.05). The diagnostic sensitivity, specificity and AUC was 84.78%, 78.26% and 0.88 respectively forserum TK1 as reference for colorectal diagnosis. The pearson correlation test was used to evaluate the serum miR-183 and TK1 correlation in colorectal cancer patients. However, no significant correlation between serum miR-183 and TK1 was found in colorectal patients (p>0.05).ConclusionSerum levels of miR-183 and TK1 arepotential biomarkers for colorectal cancer auxiliary diagnosis.

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Serum TK1 is a more reliable marker than CEA and AFP for cancer screening in a study of 56,286 people

Cited by 37 publications

References 15 publications

Microarray Expression Profiling of microRNAs Reveals Potential Biomarkers for Hepatocellular Carcinoma

Microarray Expression Profiling of microRNAs Reveals Potential Biomarkers for Hepatocellular Carcinoma

Novel monoclonal antibodies against thymidine kinase 1 and their potential use for the immunotargeting of lung, breast and colon cancer cells

The diagnostic value of serum microRNA-183 and TK1 as biomarkers for colorectal cancer diagnosis

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