Elucidation of genotype-phenotype relation in pituitary tumor through novel proteomics analysis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08880
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Chiba University
• Principal Investigator: HORIGUCHI Kentaro 千葉大学, 医学部附属病院, 講師 (50436408)
• Co-Investigator(Kenkyū-buntansha): 田中 知明 千葉大学, 大学院医学研究院, 教授 (50447299)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 下垂体腺腫 / 遺伝子型―表現型連関 / プロテオミクス / マルチオミクス

Outline of Final Research Achievements

We performed RNA-sequencing and non-targeted proteomics using pituitary adenoma tumor samples. mRNA and protein expression in the tumor tissue showed a positive correlation, and no differences were observed between tumors. Analysis using UMAP confirmed that both RNA-sequencing and protein expression were divided into well-known lineages, suggesting that the molecular and cellular biology basis of metabolic and biological functions in the tumor tissue of pituitary adenomas may affect the correlation between mRNA and protein expression. However, it was also found that there are limitations to multi-omics data analysis using "bulk samples" of the entire tumor tissue.

Free Research Field

内分泌学，脳神経外科学

Academic Significance and Societal Importance of the Research Achievements

下垂体腺腫における遺伝子型―表現型連関の解明を目的とした本研究においては、新たな技術である網羅的タンパク定量解析(non-target proteomics)およびRNA-sequencingにおけるMulti-omics data解析を用いることで、機能性と腫瘍性の次元軸から表出される多彩で複雑な下垂体腺腫の臨床像を説明し得る分子細胞生物学的交絡因子の一端を探索することができた。本研究によって得られた知見及び既存の遺伝子変異解析情報を有効に活用することにより、下垂体腫瘍の分子生物学的背景を解明することで，薬剤治療反応性や手術リスク及び寛解予測を目指した革新的個別化医療の創出をが期待される。