Microarray expression profiling identifies genes, including cytokines, and biofunctions, as diapedesis, associated with a brain metastasis from a papillary thyroid carcinoma.
Brain metastatic papillary thyroid carcinomas (PTCs) are afflicted with unfavorable prognosis; however, the underlying molecular genetics of these rare metastases are virtually unknown. In this study, we compared whole transcript microarray expression profiles of aBRAFmutant, brain metastasis from a PTC, including its technical replicate (TR), with eight non-brain metastatic PTCs and eight primary brain tumors. The top 95 probe sets (false discovery rate (FDR)p-value < 0.05 and fold change (FC) > 2) that were differentially expressed between the brain metastatic PTC, including the TR, and both, non-brain metastatic PTCs and primary brain tumors were in the vast majority upregulated and comprise, e.g.ROS1,MYBPH,SLC18A3,HP,SAA2-SAA4,CP,CCL20,GFAP,RNU1-120P,DMBT1,XDH,CXCL1,PI3, andNAPSA. Cytokines were represented by 10 members in the top 95 probe sets. Pathway and network analysis (p-value < 0.05 and FC > 2) identified granulocytes adhesion and diapedesis as top canonical pathway. Most significant upstream regulators were lipopolysaccharide, TNF, NKkB (complex), IL1A, and CSF2. Top networks categorized under diseases & functions were entitled migration of cells, cell movement, cell survival, apoptosis, and proliferation of cells. Probe sets that were significantly shared between the brain metastatic PTC, the TR, and primary brain tumors includeCASP1,CASP4,C1R,CC2D2B,RNY1P16,WDR72,LRRC2,ZHX2,CITED1, and the noncoding transcript AK128523. Taken together, this study identified a set of candidate genes and biofunctions implicated in, so far nearly uncharacterized, molecular processes of a brain metastasis from a PTC.
Center of Excellence in Genomic Medicine Research, King Abdulaziz UniversityJeddah, Saudi Arabia; KACST Technology Innovation Center in Personalized Medicine, King Abdulaziz UniversityJeddah, Saudi Arabia.
Hans-Juergen
HJ
Schulten
King Fahad Medical Research Center, King Abdulaziz University Jeddah, Saudi Arabia.
Deema
D
Hussein
Center of Excellence in Genomic Medicine Research, King Abdulaziz UniversityJeddah, Saudi Arabia; Department of Biology, King Abdulaziz UniversityJeddah, Saudi Arabia.
Fatima
F
Al-Adwani
Center of Excellence in Genomic Medicine Research, King Abdulaziz UniversityJeddah, Saudi Arabia; KACST Technology Innovation Center in Personalized Medicine, King Abdulaziz UniversityJeddah, Saudi Arabia.
Sajjad
S
Karim
Department of Pathology, Faculty of Medicine, King Abdulaziz University HospitalJeddah, Saudi Arabia; Department of Pathology, King Faisal Specialist Hospital and Research CenterJeddah, Saudi Arabia.
Jaudah
J
Al-Maghrabi
Department of Biology, King Abdulaziz University Jeddah, Saudi Arabia.
Mona
M
Al-Sharif
Department of Pathology, Faculty of Medicine, King Abdulaziz University Hospital Jeddah, Saudi Arabia.
Awatif
A
Jamal
Center of Excellence in Genomic Medicine Research, King Abdulaziz UniversityJeddah, Saudi Arabia; Institute of Cellular Medicine, Newcastle UniversityNewcastle NE2 4HH, United Kingdom.
Sherin
S
Bakhashab
Institute of Cellular Medicine, Newcastle University Newcastle NE2 4HH, United Kingdom.
Jolanta
J
Weaver
Department of Pathology, Faculty of Medicine, King Abdulaziz University Hospital Jeddah, Saudi Arabia.
Fahad
F
Al-Ghamdi
Division of Neurosurgery, Department of Surgery, King Abdulaziz University Hospital Jeddah, Saudi Arabia.
Saleh S
SS
Baeesa
Division of Neurosurgery, Department of Surgery, King Abdulaziz University Hospital Jeddah, Saudi Arabia.
Mohammed
M
Bangash
Center of Excellence in Genomic Medicine Research, King Abdulaziz UniversityJeddah, Saudi Arabia; KACST Technology Innovation Center in Personalized Medicine, King Abdulaziz UniversityJeddah, Saudi Arabia.
Adeel
A
Chaudhary
Center of Excellence in Genomic Medicine Research, King Abdulaziz UniversityJeddah, Saudi Arabia; KACST Technology Innovation Center in Personalized Medicine, King Abdulaziz UniversityJeddah, Saudi Arabia.
Mohammed
M
Al-Qahtani
Papillary thyroid carcinoma; brain metastasis; cytokines; diapedesis; microarray expression profiling