Heat shock protein 27 as a prognostic and predictive biomarker in pancreatic ductal adenocarcinoma
نویسندگان
چکیده
A role of heat shock protein 27 (HSP27) as a potential biomarker has been reported in various tumour entities, but comprehensive studies in pancreatic cancer are lacking. Applying tissue microarray (TMA) analysis, we correlated HSP27 protein expression status with clinicopathologic parameters in pancreatic ductal adenocarcinoma specimens from 86 patients. Complementary, we established HSP27 overexpression and RNA-interference models to assess the impact of HSP27 on chemo- and radiosensitivity directly in pancreatic cancer cells. In the TMA study, HSP27 expression was found in 49% of tumour samples. Applying univariate analyses, a significant correlation was found between HSP27 expression and survival. In the multivariate Cox-regression model, HSP27 expression emerged as an independent prognostic factor. HSP27 expression also correlated inversely with nuclear p53 accumulation, indicating either protein interactions between HSP27 and p53 or TP53 mutation-dependent HSP27-regulation in pancreatic cancer. In the sensitivity studies, HSP27 overexpression rendered HSP27 low-expressing PL5 pancreatic cancer cells more susceptible towards treatment with gemcitabine. Vice versa, HSP27 protein depletion in HSP27 high-expressing AsPC-1 cells caused increased gemcitabine resistance. Importantly, HSP27 expression was inducible in pancreatic cancer cell lines as well as primary cells. Taken together, our study suggests a role for HSP27 as a prognostic and predictive marker in pancreatic cancer. Assessment of HSP27 expression could thus facilitate the identification of specific patient subpopulations that might benefit from individualized treatment options. Additional studies need to clarify whether modulation of HSP27 expression could represent an attractive concept to support the incorporation of hyperthermia in clinical treatment protocols for pancreatic cancer.
منابع مشابه
Expression and clinical significance of HSPA2 in pancreatic ductal adenocarcinoma
BACKGROUND It has been shown that heat shock-related 70-kDa protein 2 (HSPA2), a member of the HSP70 family of heat shock proteins, is important for cancer cell growth and metastasis. However, the status of HSPA2 expression and its prognostic significance in pancreatic cancer remain unknown. METHODS Quantitative reverse transcriptase ploymerase chain reaction (qRT-PCR) was applied to examine ...
متن کاملElevated GRP78 expression is associated with poor prognosis in patients with pancreatic cancer
Glucose-regulated protein 78 (GRP78) is a member of the heat-shock protein 70 family. We evaluated the expression of GRP78 using tissue microarray-based immunohistochemistry in tumor tissues and adjacent nontumor tissues from 180 pancreatic ductal adenocarcinoma (PDAC) patients. The associations between the expression levels of GRP78, clinicopathological factors, and overall survival were evalu...
متن کاملExpression of novel tumor markers of pancreatic adenocarcinomas in intrahepatic cholangiocarcinomas
Intrahepatic cholangiocarcinomas (IHCCs) are morphologically and biologically similar to pancreatic ductal adenocarcinomas (PDACs), so newly identified PDAC-associated genes or proteins could provide clues for screening novel biomarkers for IHCC. In this study, the expression of three novel PDAC tumor markers (T-box transcription factor-4 [TBX4], heat shock protein-60 [HSP60], and Parkinson pro...
متن کاملStromal Annexin A2 expression is predictive of decreased survival in pancreatic cancer
Pancreatic ductal adenocarcinoma (PDA) is renowned for high rates of metastasis and poor survival. Its notoriously dense fibrotic stroma contributes to chemoresistance. Stromal signaling in PDA is recognized for its multiple roles in regulating tumor invasion and metastasis. However, no stromal biomarker which can predict survival in PDA exists. Annexin A2 (AnxA2) was formerly identified as a m...
متن کاملIdentification and Validation of a Diagnostic and Prognostic Multi-Gene Biomarker Panel for Pancreatic Ductal Adenocarcinoma
Citation: Klett H, Fuellgraf H, Levit-Zerdoun E, Hussung S, Kowar S, Küsters S, Bronsert P, Werner M, Wittel U, Fritsch R, Busch H and Boerries M (2018) Identification and Validation of a Diagnostic and Prognostic Multi-Gene Biomarker Panel for Pancreatic Ductal Adenocarcinoma. Front. Genet. 9:108. doi: 10.3389/fgene.2018.00108 Identification and Validation of a Diagnostic and Prognostic Multi-...
متن کامل