Exploring Prognostic Factors of Metastasis/Metastatic Organs By RNA-Sequencing Analysis of 22 Cases of Pheochromocytoma (Pheo) Tumor Samples

Presentation Number: MON 399
Date of Presentation: April 3rd, 2017

Masanori Fujimoto*1, Tomoko Takiguchi1, Hidekazu Nagano1, Ikki Sakuma1, Akitoshi Nakayama1, Ai Tamura1, Azusa Yamato1, Eri Komai1, Akina Shiga1, Takashi Kohno1, Seiichirou Higuchi1, Sawako Suzuki1, Hisashi Koide1, Noriko Kimura2, Koutaro Yokote1 and Tomoaki Tanaka3
1Chiba University Graduate School of Medicine, Chiba, Japan, 2National Hospital Organization Hakodate Hospital,, Hakodate, Japan, 3Chiba University Graduate School of Medicine, Chiba-city, Japan

Abstract

Introduction

Recent genome-wide analysis showed some molecular mechanisms of Pheo. On the other hand, there are clinical problems such as recurrent/metastatic cases several years after surgery. Therefore, we explored candidate genes as prognostic markers by using RNA-sequencing analysis.

Materials and Methods:

22 cases of Pheo tumor tissue samples (benign/malignant=16/6cases, male/female=9/13, gene mutation 9cases; 41%). 30 samples in total (primary/metastatic=22/8). We analyzed tumor tissue by RNA-sequencing and examined followings.

(1) Differentially expressing genes (DEG), MA plot and Gene ontology analysis comparing gene expressions of benign lesions with malignant lesions. (2) Relationships of metastatic lesions and gene expression profile. (3) Verification by qPCR and immunohistochemistry.

Results:

In dendrogram, main principle analysis and heatmap, benign lesions and malignant lesions are separated. Interestingly, in malignant cases, gene expression profile of primary lesion and metastatic lesion are quite similar (non-DEG; 85-95%). And we compared gene expression profile of lung metastatic cases and liver metastatic cases and found a lot of DEG which might have some relationships with metastatic organs. Besides, comparing benign and malignant lesions, we focused on the most differentially expressing genes (top 22 genes; HHIPL2, ACTL8, RSPO1 etc) as candidate gene of prognostic markers. The result of qPCR and immunohistochemistry was consistent with that of RNA-sequencing.

Discussion:

Genome-wide analysis might suggest that molecular trait of primary tumor of Pheo provide malignancy or metastatic organs. These approach could be useful for exploring candidate gene markers for malignancy or metastatic organs.

 

Disclosure: TT: Investigator, ONO-Pharma. Nothing to Disclose: MF, TT, HN, IS, AN, AT, AY, EK, AS, TK, SH, SS, HK, NK, KY