N. T. Fackche1, Y. Mei1, T. Ito1, M. Garner1, P. Huang1, M. V. Brock1 1The Johns Hopkins University School Of Medicine,Surgical Oncology,Baltimore, MD, USA
Introduction:
Disparities in cancer outcomes disproportionally affect minorities and underserved populations, a fact traditionally ascribed to social determinants of health. Recent literature, however, points to ethnicity-driven differential expression of cancer genes as a contributing factor. The advent of liquid biopsy tools such as Protein Functional Effector RNAs (pfeRNA) could be a key to facilitate non-invasive, cost-effective cancer detection and risk-stratification especially in resource-constrained areas of the world. PfeRNAs are small non-coding RNAs that are abundant in plasma, and have known roles in lung cancer tumorigenesis. There is recent evidence that pfeRNA genes also may be differentially expressed based on ethnicity. Our objective is to identify pfeRNAs biomarkers with discriminative potential for clinical risk-stratification in African Americans (AA) with Non-Small Cell Lung Cancer(NSCLC).
Methods:
The expression levels of 28 target pfeRNAs genes previously identified through next-generation gene sequencing were quantified in the plasma sample of 37 AA. The cohort comprised 28 cancers and nine controls from a prospectively maintained biospecimen database. Clinical characteristics were collected via a retrospective chart review. A statistical algorithm was used to design a composite biomarker by combining select pfeRNAs levels and clinical factors.
Results:
Seven of the 28 targets were clinically relevant (A-D, A-E, C-D, C-H, E-H, F-G, and G-H). PfeRNA A-E performed best as a single marker to differentiate cancer from controls with a sensitivity of 90%, a specificity of 80%, and AUC of 94.6% (P= 0.004). A computer-generated composite biomarker [formula: 3.29*Age -78.96*male+ (-38.00)*A.D+ 16.45*C.H+ 5.94*E.H -24.88*F.G+ 16.25*G.H+ (-123.08)*(A.E>=4.562104) +40] was derived and performed with an accuracy of 100% in the detection of cancer (P = 0). PfeRNA C-D demonstrated a statistically significant correlation with overall survival in the cancer subgroup N(28). Among 12 patients with C-D< (-6.69), no one died during the 12 years of follow-up. However, six of sixteen with C-D >= (-6.69) died within the first five years.
Conclusion:
PfeRNAs demonstrate excellent potential as both clinically relevant diagnostic and prognostic tools for AAs with NSCLC.These findings improve the prospect of developing population-specific clinical assays to help guide treatment strategies in impoverished areas of the world with poor access to CT scanning as well as for economically advanced countries enrolling smokers to lung cancer screening programs. While these results are promising, the small sample size precludes a definitive conclusion. Subsequent studies in larger cohorts are therefore needed to validate these findings
