Abstract
Pancreatic cancer is one of the most aggressive human malignancies and ninth leading cause of cancer death in the world. Most patients diagnosed with pancreatic cancer die within 6 months, and only 4% survive 5 years after diagnosis. Approximately one-fifth of patients with presumably ‘curable’ Pancreatic Ductal Adenocarcinoma (PDA) experience impending relapse and death, making surgical removal almost futile. Early diagnostic, prognostic and predictive biomarkers and better therapeutic options which could help personalize treatment regimens are desperately needed to improve the survival rate of pancreatic cancer patients. By employing BxPC-3 cell line model, high throughput comparative, quantitative and system proteomic analysis, we have been able to identify annexin-a4, annexin-a5 annexin a-11, caveolin-1, EGFR, H-RAS, Integrin-α6β4 proteins which were significantly upregulated in oxidatively stressed BxPC-3 cells. The present investigations have shown the presence of quite robust oxidative response in BxPC-3 cells as compared to HPDE control. The high throughput proteomic and bioinformatic analysis have shown the aberrantly regulated Cav-1-Fyn-SOS-cRAF-ERK (where Cav-1 is caveolin-1) signaling pathway, reveals that oxidative stress might activate Cav-1 protein in the membrane which in turn activate the downstream proto-oncogene tyrosine-kinase Fyn and triggers MAPK/ERK pathway. The data suggest that the above stated proteins could be used as diagnostic and prognostic biomarkers and using Cav-1-Fyn-SOS-cRAF-ERK pathway better therapeutic options could be explored.
Highlights
Pancreatic cancer is one of the most aggressive human malignancies and ninth leading cause of cancer death in the world [1]
Pancreatic cancer is characterized by colossal local invasion and early metastatic growth to the liver and regional lymph nodes [2]
Even if pancreatic cancer is surgically resected in stage I or II, it may recur at a metastatic site
Summary
Pancreatic cancer is one of the most aggressive human malignancies and ninth leading cause of cancer death in the world [1]. The incidence rate of pancreatic cancer has increased significantly in recent years [3] It is often detected in stage III resulting in an un-resectable tumor at the time of diagnosis. The recent line of investigations suggests the successive accumulation of mutations that include activation of the KRAS2 oncogene, inactivation of the tumor-suppressor genes like CDKN2A and TP53 and SMAD4 [8] This sequence of events in pancreatic carcinogenesis is supported by studies in genetically engineered mouse models in which targeted activation of Kras with concomitant inactivation of Trp or Cdkn2A results in the development of pancreatic cancer. The recent extensive genetic analysis of 24 pancreatic cancer genomes exhibited an average of 63 genetic abnormalities per tumor, mainly point mutations These abnormalities can be organized in 12 functional cancer-relevant pathways [9]. The high through put proteomic analysis and systems biology approach was adapted to identify the aberrantly regulated signaling pathway in Pancreatic Ductal Adenocarcinoma (PDAC)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
