The prognostic and predictive role of class III β-Tubulin and hENT1 expression in patients with advanced pancreatic ductal adenocarcinoma

Sahin T., IŞIK A., Guven D., Ceylan F., BABAOĞLU B., AKYOL A., ...Daha Fazla

Pancreatology, cilt.24, sa.2, ss.279-288, 2024 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 24 Sayı: 2
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1016/j.pan.2024.01.009
  • Dergi Adı: Pancreatology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CAB Abstracts, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.279-288
  • Anahtar Kelimeler: Class III β-tubulin (TUBB3), FOLFIRINOX, Gemcitabine and nabpaclitaxel (GnP), Pancreatic cancer, The human equilibrative nucleoside transporter 1 (hENT1)
  • Hacettepe Üniversitesi Adresli: Evet

Özet

Background: FOLFIRINOX and gemcitabine-nabpaclitaxel (GnP) are standard first-line treatment regimens for advanced pancreatic ductal adenocarcinoma (PDAC). However, currently, there is a lack of predictive biomarkers to aid in the treatment selection. We aimed to explore the prognostic and predictive value of class III β-Tubulin (TUBB3) and human equilibrative nucleoside transporter 1 (hENT1) expression, which have previously been shown to be associated with taxane and gemcitabine resistance in advanced PDAC. Methods: We conducted a retrospective analysis of 106 patients with advanced PDAC treated with GnP and/or FOLFIRINOX at our institution. TUBB3 and hENT1 immunohistochemical staining was performed on tumor specimens and subsequently evaluated based on the intensity and percentage of expression. Results: In patients who received the GnP regimen, a high combined score (TUBB3low/hENT1high) was associated with a higher DCR and longer PFS compared to those with intermediate (TUBB3high/hENT1high or TUBB3low/hENT1low) and low score (TUBB3high/hENT1low). In the multivariate analysis, a high combined score was an independent predictor of higher DCR (OR:11.96; 95 % CI:2.61–54.82; p = 0.001) and longer PFS (HR:0.33; 95%CI:0.18–0.60; p < 0.001). However, there was no difference in response rates or PFS based on TUBB3 and hENT1 expression among patients receiving the FOLFIRINOX regimen. Conclusion: Our findings indicate that tumor TUBB3 and hENT1 expression may predict the efficacy of the GnP regimen, and low TUBB3 and high hENT1 expression (TUBB3low/hENT1high) are associated with a higher DCR and longer PFS in patients treated with GnP. Evaluating TUBB3 and hENT1 jointly can identify the patients most (as well as least) likely to benefit from GnP chemotherapy.