Serum molecular signature for proliferative diabetic retinopathy in Saudi patients with type 2 diabetes.
The risk of vision loss from proliferative diabetic retinopathy (PDR) can be reduced with timely detection and treatment. We aimed to identify serum molecular signatures that might help in the early detection of PDR in patients with diabetes.



A total of 40 patients with diabetes were recruited at King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia, 20 with extensive PDR and 20 with mild non-proliferative diabetic retinopathy (NPDR). The two groups were matched in age, gender, and known duration of diabetes. We examined the whole genome transcriptome of blood samples from the patients using RNA sequencing. We built a model using a support vector machine (SVM) approach to identify gene combinations that can classify the two groups.



Differentially expressed genes were calculated from a total of 25,500 genes. Six genes (CCDC144NL, DYX1C1, KCNH3, LOC100506476, LOC285847, and ZNF80) were selected from the top 26 differentially expressed genes, and a combinatorial molecular signature was built based on the expression of the six genes. The mean area under receiver operating characteristic (ROC) curve was 0.978 in the cross validation. The corresponding sensitivity and specificity were 91.7% and 91.5%, respectively.



Our preliminary study defined a combinatorial molecular signature that may be useful as a potential biomarker for early detection of proliferative diabetic retinopathy in patients with diabetes. A larger-scale study with an independent cohort of samples is necessary to validate and expand these findings.
Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, MD.
Jianbo
J
Pan
Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, MD.
Sheng
S
Liu
Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA; Berman-Gund Laboratory for the Study of Retinal Degenerations, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA.
Michael
M
Farkas
Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA; Berman-Gund Laboratory for the Study of Retinal Degenerations, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA.
Mark
M
Consugar
Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, MD.
Donald J
DJ
Zack
Vitreoretina Division, King Khaled Eye Specialist Hospital, Riyadh 11462, Kingdom of Saudi Arabia.
Igor
I
Kozak
Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, MD; Vitreoretina Division, King Khaled Eye Specialist Hospital, Riyadh 11462, Kingdom of Saudi Arabia.
J Fernando
JF
Arevalo
Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA; Berman-Gund Laboratory for the Study of Retinal Degenerations, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA.
Eric
E
Pierce
Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, MD; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD.
Jiang
J
Qian
Vitreoretina Division, King Khaled Eye Specialist Hospital, Riyadh 11462, Kingdom of Saudi Arabia.
Eman
E
Al Kahtani
D000368:Aged; D015415:Biomarkers / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D003930:Diabetic Retinopathy / Q000097:blood*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D012313:RNA / Q000097:blood; D012372:ROC Curve; D012307:Risk Factors; D012529:Saudi Arabia; D012680:Sensitivity and Specificity
D015415:Biomarkers; D012313:RNA