The prognostic and predictive role of tubulin beta III and HENT1 expression in patients with advanced pancreatic adenocarcinoma

The aim of this study is to investigate the prognostic and predictive role of Class III β-tubulin (TUBB3) and human equilibrative in nucleoside transporter 1 (hENT1) expression in patients with advanced pancreatic adenocarcinoma and to evaluate the effect of the combined use of these two biomarkers on prognosis and chemotherapy response. Between January 2013 and March 2022, we enrolled 106 adult patients with locally advanced or metastatic pancreatic adenocarcinoma, who were followed up at Hacettepe University Medical Oncology Department. This retrospective study was restricted to patients with histologically diagnosed pancreatic adenocarcinoma and available tumor sample tissue for immunohistochemical analyses. Baseline characteristics, chemotherapy regimens in the first and second line, progression dates, response to chemotherapy and survival times were evaluated. The expression of TUBB3 and hENT1 in tumor tissues was divided into two as low or high compared to the median H-score. According to the combined biomarker score developed by using TUBB3 and hENT1expression together, the group with TUBB3low and HENT1high is defined as "high", the group with TUBB3low and HENT1low or TUBB3high and HENT1high as "intermediate" and the group with TUBB3high and HENT1low as "low" combined biomarker score. TUBB3 and hENT1 expression is not correlated with progression-free survival (PFS), overall survival (OS), and disease control rate (DCR) in patients receiving FOLFIRINOX as a first-line treatment regimen or in the whole patients. Although there was a trend towards increased PFS and OS with low TUBB3 and high hENT1 expression in patients receiving gemcitabine-nabpaclitaxel as a first-line treatment , it did not reach statistical significance. However, low TUBB3 and high hENT1 expression is associated with a significantly higher DCR. High combined biomarker score (TUBB3low and HENT1high) was associated with longer PFS and higher DCR in patients treated with gemcitabine-nabpaclitaxel as any line of treatment. In multivariate analysis, high combined immunohistochemical score was associated with longer PFS (HR:0,33, 95% CI 0,18-0,60, p<0,001) and longer OS (HR:0,46, 95%CI 0,24-0,88, p=0,020). In conclusion, co-evaluation of TUBB3 and hENT1 expression can be used as a novel marker predicting chemotherapy response and prognosis in patients with advanced pancreatic cancer and may contribute to the selection of first-line chemotherapy regimen and personalized chemotherapy treatment.