Salivary extracellular RNA biomarkers for insulin resistance detection in hispanics

Abstract

Aims Insulin resistance (IR) detection is challenging and no test is currently used in clinical practice. We developed salivary biomarkers that could be used for IR detection. Methods We collected saliva from 186 healthy and 276 pre-diabetic participants, divided them into high and low IR groups based on a HOMA cutoff of 2.5. We profiled extracellular transcriptome by microarray in saliva supernatant from 23 high IR and 15 low IR participants, and pre-validated the top ten extracellular mRNA (exRNA) markers in a new cohort of 40 high and 40 low IR participants. A prediction panel was then built and validated in an independent cohort of 149 high and 195 low IR participants. Results Transcriptomic analyses identified 42 exRNA candidates differentially present in saliva of high and low IR participants. From the top ten candidates, six were individually validated (PRKCB, S100A12, IL1R2, CAMP, VPS4B, CAP1) (p<0.01) and yielded AUC values ranging from 0.66 to 0.76. Body mass index (BMI) was significant higher in high compared to low IR group with AUC of 0.66, and showed no correlation with any of candidate biomarkers. The combination of four exRNA markers (IL1R2, VPS4B, CAP1, LUZP6) with BMI achieved excellent results in the prediction panel building dataset (AUC=0.79, sensitivity=79%, specificity=64%). The prediction model was validated in an independent cohort (AUC=0.82, sensitivity=63%, specificity=92%). Conclusions A panel of four salivary exRNA biomarkers (IL1R2, VPS4B, CAP1, LUZP6) and BMI was validated that can distinguish high and low IR participants, overall and in subgroups of healthy and pre-diabetic participants.

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“…The rest two genes LUZP6 and PLCB2 were not implicated earlier in obesity or related diseases. However, an extracellular transcriptome study in saliva demonstrated that four extracellular RNA biomarkers including LUZP6 had the potential to distinguish high and low insulin resistance participants [ 36 ]. Gene PLCB2 was shown to exhibit diagnostic value for hepatocellular carcinoma [ 37 ], PLCB2 also have an important role in the progression of Alzheimer’s disease and enriched in another neurodegenerative disorder Huntington’s disease [ 38 ].…”

A Circulating Exosome RNA Signature Is a Potential Diagnostic Marker for Pancreatic Cancer, a Systematic Study

“…Another study showed that the LUZP6 protein was positive in the majority of glioblastoma [ 71 ], suggesting that it may also be related to tumorigenesis. Interestingly, LUZP6 RNA is enriched in salivary exosomes and, together with another three genes ( IL1R2 , VPS4B and CAP1 ) comprising an RNA signature, could distinguish high from low insulin resistance as an extracellular RNA marker [ 72 ].…”

Liquid Biopsy: A Game Changer for Type 2 Diabetes

“…Subsequently, a validated panel comprising four salivary extracellular RNA biomarkers (IL1R2—interleukin 1 receptor type 2, VPS4B—vacuolar protein sorting 4 homolog B, CAP1—cyclase-associated actin cytoskeleton regulatory protein 1, LUZP6—leucine zipper protein 6) along with body mass index (BMI) has been identified. This panel demonstrates the capability to differentiate individuals with high and low insulin resistance, both in the general population and within subgroups of participants who are healthy and pre-diabetic [ 88 ].…”