Tumor Biology

, Volume 37, Issue 7, pp 8923–8930 | Cite as

Integrative proteomics and transcriptomics identify novel invasive-related biomarkers of non-functioning pituitary adenomas

  • Sheng-Yuan Yu
  • Li-Chuan Hong
  • Jie Feng
  • You-Tu Wu
  • Ya-Zhuo Zhang
Original Article


Non-functioning pituitary adenomas (NFPAs) are usually macroadenomas and display invasion into surrounding tissues. The treatment for invasive NFPAs is still challenging. This study describes the differential patterns of gene expression between invasive and non-invasive NFPAs and identifies novel biomarkers involved in invasion of NFPAs for diagnosis and treatment. Using gene microarray technology, we examined the gene expression profile and found 1160 differentially expressed messenger RNA (mRNA) between invasive and non-invasive NFPAs. Then, we examined the protein profile by liquid chromatography tandem mass spectrometry (LC-MS/MS) and found 433 differentially expressed proteins between invasive and non-invasive NFPAs. Subsequently, we integrated the proteomics and transcriptomics datasets and identified 29 common changed molecules. Through bioinformatics analysis using Ingenuity Pathway Analysis (IPA) software, we showed that the 29 molecules were enriched in 25 canonical signaling pathways, 25 molecular and cellular functions, and 2 networks. Eight genes were identified involved in the invasion function by the molecular and cellular functions analysis, including CAT, CLU, CHGA, EZR, KRT8, LIMA1, SH3GLB2 and SLC2A1. Furthermore, we validated the decreased CHGA expression and increased CLU expression in invasive NFPAs by qRT-PCR and Western blot. Our study demonstrated that integration of proteomics and transcriptomics could prove advantageous for accelerating tumor biomarker discovery and CHGA and CLU might be important novel biomarkers and therapeutic targets for invasion of NFPAs.


Non-functioning pituitary adenomas Proteomics Transcriptomics Clusterin Chromogranin A 



Non-functioning pituitary adenomas


Liquid chromatography tandem mass spectrometry


Ingenuity pathway analysis


Magnetic resonance imaging


Ribonucleic acid


Chromogranin A




Real-time quantitative reverse transcription polymerase chain reaction.



The authors thank the subjects for donating DNA samples. The study is supported by the Research Special Fund for Public Welfare Industry of Health (201402008), the National High Technology Research and Development Program of China (863 Program), and the National Natural Science Foundation of China.

Authors’ contributions

SYY and LCH participated in the study design and wrote the paper. SYY, LCH, and YTW carried out the experimental studies. JF and YZZ participated in manuscript revision. All authors read and approved the final manuscript.

Compliance with ethical standards

Conflicts of interest


Supplementary material

13277_2015_4767_MOESM1_ESM.docx (57 kb)
Table S1 (DOCX 56 kb)
13277_2015_4767_MOESM2_ESM.docx (58 kb)
Table S2 (DOCX 58 kb)
13277_2015_4767_MOESM3_ESM.docx (58 kb)
Table S3 (DOCX 58 kb)
13277_2015_4767_Fig5_ESM.jpg (76 kb)
Fig. S1

The 25 significant canonical signaling pathways (JPG 75 kb)

13277_2015_4767_MOESM4_ESM.tif (252 kb)
High resolution image (TIF 251 kb)
13277_2015_4767_Fig6_ESM.jpg (127 kb)
Fig. S2

The IPA legend of molecule shapes and colors as well as relationship labels and types (JPG 126 kb)

13277_2015_4767_MOESM5_ESM.tif (380 kb)
High resolution image (TIF 380 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Sheng-Yuan Yu
    • 1
  • Li-Chuan Hong
    • 2
  • Jie Feng
    • 2
  • You-Tu Wu
    • 2
  • Ya-Zhuo Zhang
    • 1
  1. 1.Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Beijing Institute for Brain Disorders Brain Tumor Center, China National Clinical Research Center for Neurological DiseasesCapital Medical UniversityBeijingChina
  2. 2.Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina

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