Mcl-1 expression is a predictive marker of response to gemcitabine plus nab-paclitaxel for metastatic pancreatic cancer

Sci Rep. 2024 Sep 20;14(1):21953. doi: 10.1038/s41598-024-73020-8.

Abstract

Antiapoptotic protein, including Mcl-1, expression is frequently observed in pancreatic cancer. Gemcitabine plus nabpaclitaxel (GnP) is the standard chemotherapy for metastatic pancreatic cancer (MPC); however, predictive markers for its efficacy remain unestablished. This study evaluated the association between GnP's therapeutic effects and Mcl-1 expression in tissue samples obtained using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic tumor or percutaneous ultrasound-guided biopsy for metastatic liver tumor. We retrospectively reviewed 38 patients with histologically diagnosed MPC who received GnP as the first-line chemotherapy at our institute between December 2014 and July 2018. Post-immunohistochemistry analysis for Mcl-1 expression detection, patients were divided to into two groups based on the cell proportion showing Mcl-1 immunoreactivity: positive (> 20%; 23 [60.5%] patients) and negative (≤ 20%; 15 [39.5%] patients) groups. Clinical characteristics did not differ between the two groups. The Mcl-1 positive group showed a significantly higher disease control rate (95.7% vs. 73.3%; P = 0.046), longer progressionfree survival (PFS) (7.2 months vs. 4.9 months; P = 0.018) and longer overall survival (OS) (14.9 months vs. 9.2 months; P = 0.008) than the Mcl-1 negative group. Multivariate analysis showed that Mcl-1 expression was an independent predictive marker for PFS and OS. Mcl-1 expression could be a predictive marker for favorable response to GnP.

Keywords: Anti-apoptotic protein; Chemotherapy; Endoscopic ultrasound-guided fine-needle aspiration; Liver tumor biopsy; Predictive marker.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Albumins* / administration & dosage
  • Albumins* / metabolism
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Biomarkers, Tumor* / metabolism
  • Deoxycytidine* / administration & dosage
  • Deoxycytidine* / analogs & derivatives
  • Deoxycytidine* / therapeutic use
  • Female
  • Gemcitabine*
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Liver Neoplasms / secondary
  • Male
  • Middle Aged
  • Myeloid Cell Leukemia Sequence 1 Protein* / metabolism
  • Neoplasm Metastasis
  • Paclitaxel* / administration & dosage
  • Paclitaxel* / therapeutic use
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / metabolism
  • Pancreatic Neoplasms* / mortality
  • Pancreatic Neoplasms* / pathology
  • Prognosis
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Deoxycytidine
  • Gemcitabine
  • Paclitaxel
  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Biomarkers, Tumor
  • MCL1 protein, human