Biomarker discovery for neuroendocrine cervical cancer

Abstract

Neuroendocrine cervical cancer is an aggressive but rare form of cervical cancer. The majority of neuroendocrine cervical cancer patients present with advanced-stage diseases. However, the limited numbers of neuroendocrine tumor markers are insufficient for clinical purposes. Thus, we used a proteomic approach combining lysine labeling 2D-DIGE and MALDI-TOF MS to investigate the biomarkers for neuroendocrine cervical cancer. By analyzing the global proteome alteration between the neuroendocrine cervical cancer line (HM-1) and non-neuroendocrine cervical cancer lines (CaSki cells, ME-180 cells, and Hela cells), we identified 82 proteins exhibiting marked changes between HM-1 and CaSki cells, and between ME-180 and Hela cells. Several proteins involved in protein folding, cytoskeleton, transcription control, signal transduction, glycolysis, and redox regulation exhibited significant changes in abundance. Proteomic and immunoblot analyses indicated respective 49.88-fold and 25-fold increased levels of transgelin in HM-1 cells compared with that in other non-neuroendocrine cervical cancer cell lines, implying that transgelin is a biomarker for neuroendocrine cervical cancer. In summary, we used a comprehensive neuroendocrine/non-neuroendocrine cervical cancer model based proteomic approach for identifying neuroendocrine cervical cancer markers, which might contribute to the prognosis and diagnosis of neuroendocrine cervical cancer.

Proteomic Analysis of Normal and Cancer Cervical Cell Lines Reveals Deregulation of Cytoskeleton-associated Proteins

“…Comparative analysis of the secretome revealed 67 differentially expressed proteins, out of which 36 were also identified as differentially expressed in our study. Furthermore, Lin et al (51) proposed several putative biomarkers for the rare and very aggressive type of neuroendocrine cervical cancer by comparing the proteomic profile of HM-1, a neuroendocrine cervical cancer cell line, to CaSki, ME-180, and HeLa, that exhibit a non-neuroendocrine origin (51). Their study disclosed 82 differentially expressed proteins and further confirmed the differential expression of transgelin, galectin-1 and PGK-1 in all cell lines employing western blotting.…”

Targeting UDP‐glucose dehydrogenase inhibits ovarian cancer growth and metastasis

“…Colloidal Coomassie blueG‐250 staining was used to visualize CyDye‐labelled protein features in 2DE followed by performing interesting post‐stained gel pieces for MALDI‐TOF MS identification. The detailed procedures for protein staining, in‐gel digestion, and MALDI‐TOF MS analysis, and the algorithm used for data processing have been described in previous publication 16,17 . Peaks in the mass range of m/z 800‐3000 were used to generate a peptide mass fingerprint that was searched against the Swiss‐Prot/TrEMBL database (released on February 2014) with 542503 sequences using Mascot software v2.5.0.1 (Matrix Science).…”

Gel electrophoresis/electroelution sorting fractionator combined with filter‐aided sample preparation for deep proteomic analysis

“…The CaSki cell line is a human cervical cancer cell line that is widely used in cancer research. Several 2-DEproteomics-based studies searching for biomarkers, as well as studies describing the effect of cancer drugs have used the CaSki cell line [55][56][57]. However, there are few reports on the comprehensive characterization of the proteome of this HPV-16 positive human carcinoma compared to the in-depth proteome characterization of Hela, an HPV-18 positive human cervical carcinoma cell line [11].…”