Extracellular vesicle long RNA markers of early‐stage lung adenocarcinoma

Abstract

Lung cancer screening by low‐dose computed tomography (LDCT) can improve mortality rates among high‐risk individuals, especially adenocarcinoma cases with characteristically poor prognosis, although high false‐positive rates have limited its clinical application. The objective of our study was to identify biomarkers for early‐stage lung adenocarcinoma (ie, tumor diameter <2 cm) through extracellular vesicle long RNA (evlRNA) sequencing. High throughput evlRNA sequencing and support vector machine (SVM) identification of candidate diagnostic marker transcripts were performed using serum samples obtained before lung surgery. A total of 145 upregulated and 363 downregulated differential genes (P value <.05, fold change >1.5) were identified between lung adenocarcinoma (LUAD) patients and benign controls. An SVM model based on a 23‐gene signature could distinguish EV samples of LUAD patients from those of control subjects with 86.49% sensitivity, 95.00% specificity and 92.31% accuracy in the training set and 93.75% sensitivity, 85.71% specificity and 88.24% accuracy in the validation set. A 17‐gene signature was then identified that could distinguish AIS patient samples from those of MIA/IAD patients with 93.33% sensitivity, 98.00% specificity, and 96.25% accuracy in the trainingset and 83.33% sensitivity, 96.55% specificity, and 94.29% accuracy in the validation set. EvlRNAs in serum show considerable diagnostic value for screening LUAD patients with tumor sizes <2 cm in conjunction with LDCT, potentially reducing false positive rates while improving mortality rates.

Multimodal fusion of liquid biopsy and CT enhances differential diagnosis of early-stage lung adenocarcinoma

“…The methodologies employed for collection of blood samples, serum extracellular vesicle (EV) purification, RNA isolation, characterization of EVs, construction of evlRNA libraries and subsequent RNA-seq analysis closely adhere to those detailed in the previously cited work 12 . We explored the differentially expressed genes (DEGs) between the LUAD and control groups, which revealed a total of 145 upregulated and 363 downregulated DEGs ( p value < 0.05, fold change > 1.5).…”

“…Combining liquid biopsy with AI methods holds significant promise for early-stage diagnosis 9 , 10 . Extracellular vesicle long RNA (evlRNA), identified as a candidate biomarker, is enriched in the blood of lung cancer patients compared to healthy controls, showing significant diagnostic value in early-stage LUAD patients 11 , 12 . However, many current liquid biopsies focusing on early cancer detection lack the sensitivity needed for reliable identification of early-stage cancers 13 .…”

“…In addition, blood samples were collected in 10 mL K2EDTA anticoagulant vacutainer tubes. Subsequent steps for serum extracellular vesicle (EV) purification, RNA isolation and RNA-seq analysis followed procedures from our prior study 12 . We selected 17 evlRNA features from differentially expressed genes (DEGs) between the LUAD and control groups.…”

Liquid biopsy techniques and lung cancer: diagnosis, monitoring and evaluation

“…This suggests that EVs can serve as biomarkers for the detection of precancerous lesions. Current methods for diagnosing early lung cancer using EVs are inclined towards the detection of miRNA or lncRNA carried by EVs [ 139 , 140 ]. For example, the elevated expression of miR-520c-3p and miR-1274b in lung cancer can be detected by EVs for the early diagnosis of NSCLC [ 139 ].…”

Circulating noncoding RNAs: promising biomarkers in liquid biopsy for the diagnosis, prognosis, and therapy of NSCLC

“…It was found that miR-451a, miR-194-5p and miR-486-5p were significantly increased in EV in lung adenocarcinoma patients compared with healthy individuals, with an AUC of 0.993[ 31 ]. In another study, extracellular vesicle Long RNA (NFKBIA, NDUFB10, SLC7A7, ARPC5, SEPTIN9, HMGN1, H4C2, and Lnc-PLA2G1B-2) were regarded as signature of early NSCLC (diameter < 2 cm), and extracellular vesicle Long RNA can be used as a supplement to LDCT as a noninvasive biomarker for screening early NSCLC [ 32 ]. With the progression and change of the disease, the expression level of circulating ncRNA has a sensitive trend of change.…”