iTRAQ-based quantitative proteomic analysis of differentially expressed proteins in chemoresistant nasopharyngeal carcinoma

Abstract

Nasopharyngeal carcinoma (NPC) is a highly prevalent disease in Southeast Asia. The disease is typically diagnosed in the later stages, and chemotherapy resistance often causes treatment failure. To investigate the underlying mechanisms of drug resistance, we searched for chemoresistant-associated proteins in NPC and drug-resistant NPC cell lines using isobaric tags for relative and absolute quantitation combined with nano liquid chromatography-tandem mass spectrometry. The chemoresistant NPC cell lines CNE1DDP and CNE2DDP were resistant to 1 mg/L cisplatin, had resistant indexes of 4.58 and 2.63, respectively, and clearly grew more slowly than the NPC cell lines CNE1 and CNE2. Using three technical replicates, we identified 690 nonredundant proteins, 56 of which were differentially expressed in both groups of cell lines (CNE1 vs. CNE1DDP and CNE2 vs. CNE2DDP). Gene Ontology, KEGG pathway, and miRNA analyses and protein-protein interactions of differentially expressed proteins showed that proteins TRIM29, HSPB1, CLIC1, ANXA1, and STMN1, among others, may play a role in the mechanisms of chemoresistance in clinical therapy. The chemotherapy-resistant proteomic profiles obtained may allow the identification of novel biomarkers for early detection of chemoresistance in NPC and other cancers.

Downregulation of FoxM1 sensitizes nasopharyngeal carcinoma cells to cisplatin via inhibition of MRN-ATM-mediated DNA repair

“…The majority of patients present with locally advanced or metastatic NPC when newly diagnosed (18). Despite treatment, the prognosis of late stage NPC patients remains poor (19); thus, the development of targeted therapies for NPC is important.…”

Intracellular Chloride Channels: Novel Biomarkers in Diseases

“…CLIC1 is overexpressed in several cancers including liver cancer, gall bladder cancer, pancreatic ductal adenocarcinoma, glioma, breast cancer, nasopharyngeal carcinoma, and gastric cancer to name a few (Wulfkuhle et al, 2002;Petrova et al, 2008;Chang et al, 2009;Wang et al, 2009Wang et al, , 2018Tang et al, 2012;Wei et al, 2015;Jia et al, 2016;Qu et al, 2016). It is known to play a role in cell viability, possibly by modulating mitochondrial function.…”

Differential Expression and Alternative Splicing of Transcripts Associated With Cisplatin-Induced Chemoresistance in Nasopharyngeal Carcinoma

“…Cisplatin (DDP), a DNA damaging agent, exhibits its cytotoxicity and apoptosis-inducing activities by forming DNA adducts or by targeting cancer signaling pathways (Chen et al, 2015;Amable, 2016;Wang et al, 2018). Combinations of DDP-based chemotherapies have been widely used to treat various cancers, including NPC (Agbale et al, 2016;Dugbartey et al, 2016;Sun et al, 2016).…”