Heat Shock Protein 27 Expression in EUS-FNA Samples Can Predict Gemcitabine Sensitivity in Pancreatic Cancer

Abstract

Abstract. Background/Aim: Gemcitabine (GEM) Pancreatic cancer shows one of the worst prognoses among all malignant tumors since it progresses quickly and is difficult to diagnose at an early stage. Advances in chemotherapy are considered to be important for improving the prognosis of unresectable cases.Burris et al.(1) reported that gemcitabine (GEM) can significantly prolong survival in comparison to 5-FU for unresectable pancreatic cancer. Recently, FOLFIRINOX (L-OHP, CPT-11, 5-FU, LV) therapy (2) and GEM combined with nab-paclitaxel therapy (3) were shown to prolong survival. FOLFIRINOX was associated with strong toxicity, because it has not been established whether the combination therapy can be safely administered. It is thought that GEM based-chemotherapy will also be a key to the treatment of unresectable pancreatic cancer. It has been reported that recent advances in genetic analysis technology have revealed the factors involved with GEM sensitivity in pancreatic cancer cells (4, 5), and tailored therapies are expected.We identified GEM resistance-related proteins in pancreatic cancer by a proteomic analysis. We compared the expression levels of proteins in GEM-resistant pancreatic cancer cell lines with the expression in GEM-sensitive cell lines using twodimensional electrophoresis and liquid chromatography-mass spectrometry. Among them, the expression of Heat shock protein 27 (HSP27) was found to be increased in the GEMresistant cell line. Furthermore, we confirmed that GEM sensitivity was restored when the HSP27 expression in the GEM-resistant cell line was reduced (6, 7). Additionally, we clarified that the expression of phosphorylated HSP27 (p-HSP27) increased in the GEM-resistant cell line (8).In addition, the ability to predict the treatment effects using endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) samples may help in the selection of appropriate medicines for unresectable pancreatic cancer.No previous studies have evaluated the rates of HSP27 and p-HSP27 expression in pancreatic cancer cells from EUS-FNA samples. The purpose of this study was to evaluate the rates of HSP27 and p-HSP27 expression in EUS-FNA samples, and to demonstrate their association with GEM sensitivity. Materials and Methods Subjects, Examination itemsThe comparison of the rates of HSP27 expression in the EUS-FNA samples and the resected specimens. We compared the rates of HSP27 expression in EUS-FNA samples and resected specimens and evaluated the relationship with the resected specimens. The study population included 19 patients who had been diagnosed with 637 This article is freely accessible online.Correspondence to: Michitaka Kawano,

p38β (MAPK11) mediates gemcitabine-associated radiosensitivity in sarcoma experimental models

“…In addition, our report reinforces the critical role of the p38MAPK signalling pathway in the cellular response to gemcitabine in agreement with previous data showing that p38α mediates the apoptotic response to this drug [17,34]. In fact, downstream targets of p38MAPK, as MAPKAPK2 or HSP27, have been related to a resistant phenotype [35][36][37][38] and also considered as putative biomarkers [39,40].…”

EUS tissue acquisition: From A to B

“…[ 74 ] Levels of hENT1 and HSP27 in FNA tissue also seem to predict sensitivity to gemcitabine in patients with unresectable pancreatic cancer. [ 75 76 ] Only a few studies addressed the question whether FNA or FNB is superior in terms of sample adequacy for next-generation sequencing (NGS). Larson et al observed no difference between the two needle types,[ 77 ] but in a larger trial by Elhanafi et al including 167 patients, the proportion of samples sufficient for NGS was higher in the FNB group.…”

New era for pancreatic endoscopic ultrasound: From imaging to molecular pathology of pancreatic cancer

“…Expression of HSP72 on EUS-FNA samples, evaluated through IHC, was significantly associated with that on resected specimens and was a helpful predictive marker for sensitivity to gemcitabine (GEM). GEM-resistance rate was significantly higher in patients with overexpression of p-HSP27, and the survival rate was significantly lower if p-HSP27 (Ser82) detection rate was > 51.6%[45]. Another important molecular biomarker for prediction of GEM sensitivity in unresectable PDAC was S100A4 mRNA expression, analyzed in EUS-FNA samples through qRT-PCR analysis.…”