Label-free quantitative proteomics unravels the importance of RNA processing in glioma malignancy.
Glioma, one of the most common cancers in human, is classified to different grades according to the degrees of malignancy. Glioblastoma (GBM) is known to be the most malignant (Grade IV) whereas low-grade astrocytoma (LGA, Grade II) is relatively benign. The mechanism underlying the pathogenesis and progression of glioma malignancy remains unclear. Here we report a quantitative proteomic study to elucidate the differences between GBM and LGA using liquid chromatography and tandem mass spectrometry followed by label-free quantification. A total of 136 proteins were differentially expressed in GBM for at least five folds in comparison with LGA. Ontological analysis revealed a close correlation between GBM-associated proteins and RNA processing. Interaction network analysis indicated that the GBM-associated proteins in the RNA processing were linked to crucial signaling transduction modulators including epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 1 (STAT1), and mitogen-activated protein kinase 1 (MAPK1), which were further connected to the proteins important for neuronal structural integrity, development and functions. Upregulation of 40S ribosomal protein S5 (RPS5), Ferritin Heavy chain (FTH1) and STAT1, and downregulation of tenascin R (TNR) were validated as representatives by immune assays. In summary, we revealed a panel of GBM-associated proteins and the important modulators centered at the RNA-processing network in glioma malignancy that may become novel biomarkers and help elucidate the underlying mechanism.
Cancer Research Center, Shandong University School of Medicine, Jinan 250012, China; Departments of Neurosurgery and Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012, China; Brain Science Research Institute of Shandong University, Jinan 250012, China. Electronic address: tb6120@163.com.
Baibin
B
Bi
Departments of Neurosurgery and Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012, China; Brain Science Research Institute of Shandong University, Jinan 250012, China. Electronic address: 784253087@qq.com.
Feng
F
Li
Cancer Research Center, Shandong University School of Medicine, Jinan 250012, China. Electronic address: mmilvy@sohu.com.
Jisheng
J
Guo
Cancer Research Center, Shandong University School of Medicine, Jinan 250012, China. Electronic address: cuilingli@yahoo.com.
Cuiling
C
Li
Cancer Research Center, Shandong University School of Medicine, Jinan 250012, China. Electronic address: 1660341331@qq.com.
Ruirui
R
Jing
Cancer Research Center, Shandong University School of Medicine, Jinan 250012, China. Electronic address: lvxin121@163.com.
Xin
X
Lv
Cancer Research Center, Shandong University School of Medicine, Jinan 250012, China. Electronic address: jam@mail.sdu.edu.cn.
Xinjun
X
Chen
Cancer Research Center, Shandong University School of Medicine, Jinan 250012, China. Electronic address: 962295185@qq.com.
Fengqin
F
Wang
Departments of Surgery and Urology, VA Boston Healthcare System, Boston University School of Medicine, Boston, MA 02130, USA. Electronic address: kazadzoi@bu.edu.
Kazem M
KM
Azadzoi
Departments of Neurosurgery and Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012, China. Electronic address: 3394319@qq.com.
Lin
L
Wang
Departments of Neurosurgery and Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012, China; Brain Science Research Institute of Shandong University, Jinan 250012, China. Electronic address: ns3000@126.com.
Yuguang
Y
Liu
Cancer Research Center, Shandong University School of Medicine, Jinan 250012, China; Departments of Surgery and Urology, VA Boston Healthcare System, Boston University School of Medicine, Boston, MA 02130, USA. Electronic address: jyang@bu.edu.
Jing-Hua
JH
Yang
D000328:Adult; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D040901:Proteomics / Q000379:methods; D012313:RNA / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
D012313:RNA
cancer biomarker(s); cancer pathogenesis; glioblastoma; label-free quantification; mass spectrometry