TUBB Microtubule Protein Expression Level in Tumor Tissue Predicts Aggressive Course of Non-Small Cell Lung Cancer

   Background. Elevated expression of TUBB3 protein is associated with resistance to taxanes and vinca alkaloids, as well as with increased metastatic potential of tumor cells. However, studies evaluating TUBB3 expression across various tumor types, including non-small cell lung cancer (NSCLC), and its association with clinically significant disease characteristics have produced inconsistent results.

   The aim of the study. To assess the prognostic value of TUBB3 expression levels in NSCLC tissue as a molecular marker of disease aggressiveness.

   Material and methods. An analysis was conducted on overall survival in NSCLC patients (N = 120) with varying levels of TUBB3 expression in tumor tissue, assessed using an immunofluorescence method coupled with flow cytometry. Primary monoclonal antibodies against TUBB3 (EP1569Y) and secondary antibodies conjugated with DyLight650 dye were used. Fluorescence was measured on a Navios flow cytometer, and the number of stained cells was determined using the Kolmogorov–Smirnov method in FlowJo 10.0.8 software. Statistical analysis was performed using GraphPad Prism 6.0.

   Results. 1. TUBB3 expression was detected in 100 % of the analyzed NSCLC samples, with a median expression level of 40 %. 2. A reduction in patient survival and a 1.5-fold increase in hazard ratio (HR) were observed in the group with TUBB3 expression ≥ 40 % compared to < 40 %. 3. The greatest decrease in survival and the highest increase in HR (2.7- and 2.6-fold, respectively) were noted when the cutoff level for comparison was raised to ≥ 50 % versus < 50 %. 4. The greatest improvement in survival and a 1.9-fold reduction in HR were observed when the cutoff level was lowered to < 35 % versus ≥ 35 %.

   Conclusion. The level of expression of the molecular marker TUBB3, which reflects the metastatic potential of tumor cells, serves as a prognostic factor for the aggressiveness of NSCLC. TUBB3 expression level ≥ 50 % can be considered a reliable molecular indicator of aggressive disease course, while a level < 35 % is a reliable marker of a more favorable prognosis.

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