TAU Expression Profile in Different Stages of Colorectal Cancer: a Potential Biomarker in Late Stage Tumor

Background and Objective: Colorectal cancer (CRC) ranks the fourth most frequent cancer worldwide and is one of the main reasons of cancer-associated deaths. Despite early diagnosis, surgical and chemotherapeutic modalities have significantly reduced the CRC mortality rate, the survival rate for end-stage CRC patients still remains low. Cytoskeletal variations on cancer stem cells have a key function in metastasis. Microtubules are the primary components of cytoskeletons and play a crucial role in cell division, cellular and intracellular movement and maintenance of cell shape. TAU, as a micro tubular protein, is the primary component of cytoskeletons. Altered levels of the TAU gene expression seems to be encountered in different human cancers such as breast, prostate, ovary and stomach cancer. In the present study, the correlation between the TAU protein expression and different stages of CRC was investigated to assess it as a potential biomarker in CRC. Materials and Methods: Based on colorectal cancer frequencies, the estimated number of subjects was calculated using statistical formula. 20 patients with CRC were enrolled in the study. Written informed consent obtained from patients to use their sample for study purposes. Histopathology of the tumor was assessed using a part of the tissue samples by a pathologist. Formalin-fixed paraffin embedded (FFPE) tissue specimens were obtained from 4 stages of colorectal tumor tissues and corresponding tumor adjacent tissue, at Isfahan Hospital from 2016 to 2017. None of the patients had received radiotherapy or chemotherapy before surgery. Quantitative real-time PCR was performed to measure TAU expression. All measurements were done in at least triplicates. The correlation between the TAU gene expressions and different stages of cancer were also evaluated using SPSS software 23.0 statistical software. Findings: The result showed the expression of the TAU gene in tumor tissue was significantly higher than adjacent normal tissue in all stages of CRC. Significantly higher expression was observed in stage IV compared to stage I, Stage II and stage III (p<0.01), and in stage III compared to stage II and I. No significant difference was found between stage II and I. Conclusion: Our study is the first of its kind to show that TAU is directly correlated to higher stages of CRC. The TAU gene may play a key role in CRC progression and could serve as a potential predictive biomarker in CRC patients. It seems logical to consider that silencing the expression of the TAU gene might have a major effect on the therapeutic intervention of CRC in the future.

Keywords:

Colorectal cancer , TAU protein , Predictive biomarker , Prognostic biomarker