Orphan non-coding RNAs demonstrated efficacy for accurate, sensitive, and early detection of NSCLC.

“Orphan non-coding RNAs (oncRNAs) are a novel category of small non-coding RNAs that are present in the tumor tissue and blood of people with cancer and largely absent in people without cancer,” Mehran Karimzadeh, PhD, and colleagues wrote. “To examine the potential of using oncRNAs for early cancer detection via liquid biopsy, we assessed the oncRNA content of serum from people with and without non-small cell lung cancer (NSCLC) and developed a prediction model for NSCLC.”

For their analysis, Dr. Karimzadeh and colleagues collected a cohort of serum samples (N=540). They classified the samples into two cohorts. Cohort A was for training, which included 150 cases of NSCLC (30.7% female; mean age, 67.9; ever-smokers: 95.3%) and 219 controls (36.1% female; mean age, 62.4; ever-smokers: 26.9%). Cohort B included 88 cases of NSCLC (40.9% female; mean age, 62.7; ever-smokers: 89.8%) and 83 controls (54.2% female; mean age, 54.1; ever-smokers: 6.0%) and served as the internal validation group.

The researchers utilized RNA to generate and sequence libraries using next-generation sequencing. A previously created collection included NSCLC oncRNAs found in tumor tissues from 999 cases of NSCLC that were “largely absent” in 679 normal samples from The Cancer Genome Atlas (TCGA) smRNA-seq database, according to the study results. Dr. Karimzadeh and colleagues distilled this collection and yielded a final NSCLC oncRNA catalog of 81,004 distinct oncRNA species. This distilled catalog served as the reference for identifying NSCLC oncRNAs in the present study. A trained logistic regression model predicted the presence of NSCLC, which was validated in cohort B.

The findings were presented at the 2023 annual meeting of the American Association for Cancer Research.

‘Routine Blood Draw’ May Identify NSCLC Early

In total, 64,379 oncRNAs were identified from the distilled TCGA oncRNA catalog in at least one sample across both cohorts (A: N=55,650; B: N=47,539). Based on five-fold cross-validation, the area under the curve for the logistic regression model was 0.95 (95% CI, 0.93-0.97) in the training cohort and 0.98 (95% CI, 0.97-0.99) in the validation cohort. Sensitivities for detecting early-stage NSCLC (1/2) at 95% specificity were 0.78 (95% CI, 0.69-0.86) in the training cohort and 0.92 (95% CI, 0.83-0.98) in the validation cohort.

The results indicate “the potential for accurate, sensitive, and early detection of NSCLC through sequencing the oncRNA content of a routine blood draw,” Dr. Karimzadeh and colleagues wrote.

“The performance of the model trained on one cohort and internally validated in a separate cohort supports the generalizability of this approach in detecting NSCLC.”