BackgroundLung, breast, and colorectal malignancies are the leading cause of cancer-related deaths in the world causing over 2.8 million cancer-related deaths yearly. Despite efforts to improve prevention methods, early detection, and treatments, survival rates for advanced stage lung, breast, and colon cancer remain low, indicating a critical need to identify cancer-specific biomarkers for early detection and treatment. Thymidine kinase 1 (TK1) is a nucleotide salvage pathway enzyme involved in cellular proliferation and considered an important tumor proliferation biomarker in the serum. In this study, we further characterized TK1’s potential as a tumor biomarker and immunotherapeutic target and clinical relevance.MethodsWe assessed TK1 surface localization by flow cytometry and confocal microscopy in lung (NCI-H460, A549), breast (MDA-MB-231, MCF7), and colorectal (HT-29, SW620) cancer cell lines. We also isolated cell surface proteins from HT-29 cells and performed a western blot confirming the presence of TK1 on cell membrane protein fractions. To evaluate TK1’s clinical relevance, we compared TK1 expression levels in normal and malignant tissue through flow cytometry and immunohistochemistry. We also analyzed RNA-Seq data from The Cancer Genome Atlas (TCGA) to assess differential expression of the TK1 gene in lung, breast, and colorectal cancer patients.ResultsWe found significant expression of TK1 on the surface of NCI-H460, A549, MDA-MB-231, MCF7, and HT-29 cell lines and a strong association between TK1’s localization with the membrane through confocal microscopy and Western blot. We found negligible TK1 surface expression in normal healthy tissue and significantly higher TK1 expression in malignant tissues. Patient data from TCGA revealed that the TK1 gene expression is upregulated in cancer patients compared to normal healthy patients.ConclusionsOur results show that TK1 localizes on the surface of lung, breast, and colorectal cell lines and is upregulated in malignant tissues and patients compared to healthy tissues and patients. We conclude that TK1 is a potential clinical biomarker for the treatment of lung, breast, and colorectal cancer.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0633-9) contains supplementary material, which is available to authorized users.

Thymidine kinase 1 (TK1) is a well-studied cancer biomarker. It is commonly found upregulated in the serum of cancer patients, and its levels correlate with stage and grade, disease progression, and prognosis. It has recently been reported that TK1 localizes on the plasma cell membrane of hematological and solid malignancies, and not on the membrane of normal healthy cells, and while on the membrane, TK1 has enzymatic activity. However, the function of TK1 on the surface membrane is not well understood. Here, we hypothesize that it may have a role in tumor invasion and migration. It has been shown that TK1 expression levels positively correlate with epithelia to mesenchymal transition (EMT) markers in patients with breast cancer as they progress from HER2+ to triple negative breast cancer. In this study, we silenced TK1 expression by siRNA and show that TK1's membrane expression is significantly downregulated at 60 hours post transfection. Using a Matrigel-based quantitative invasion assay, we measured cell invasion potential in cells either expressing or lacking TK1 on their membrane and found that cells that lack TK1 on their membrane exhibit decreased invasion potential. These results suggest that TK1's presence on the membrane may play a role in invasion and cell migration in cancer.

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The study of the mechanism of oxidative stress and regulation of oxygen-dependent processes is important, as the establishment of a complex interaction between oxidative stress, oxidative protein damage and the body's antioxidant system makes it possible to clarify metabolic pathways of disease pathogenesis. In our study, we concluded that in patients with chronic non-specificinflammatory diseases of the genitals of men and women, the phagocytic activity of polymorphonuclear leukocytes is reduced mainly by the oxygen-dependent mechanism, and tissue - by the oxygen-independent. As an exception in patients with chlamydial infection, the phagocytic activity of tissue polymorphonuclear leukocytes was also reduced by an oxygen-dependent mechanism.