Methionyl-tRNA synthetase and aminoacyl-tRNA synthetases interacting multi-functional protein-lacking exon 2 as potential diagnostic biomarkers for lung cancer.

Cytological specimens from computed tomography (CT)-guided needle aspiration biopsy (CT-NAB) have relatively low sensitivity for lung cancer diagnosis. This study evaluated the usefulness of the dual immunofluorescence (IF) staining method using methionyl-tRNA synthetase (MARS), aminoacyl-tRNA synthetases interacting multi-functional protein-lacking exon 2 (AIMP2-DX2), and pan-cytokeratin (pan-CK) obtained from clinical specimens. One-hundred forty-five cytology specimens were prospectively collected from patients who underwent CT-NAB under the suspicion of lung cancer. The results of two combinations of MARS, AIMP2-DX2, and pan-CK dual IF staining were compared with those of conventional cytology by calculating the area under the curve (AUC). The results of combining dual IF with conventional cytology showed higher AUC than conventional cytology alone: cytology/MARS/AIMP2-DX2 (0.891 vs. 0.829, P = 0.003), cytology/MARS/pan-CK (0.916 vs. 0.829, P < 0.001), and cytology/AIMP2-DX2/pan-CK (0.877 vs. 0.829, P = 0.005). In specimens with non-diagnostic results in conventional cytology, MARS/AIMP2-DX2 dual IF staining showed sensitivity, specificity, and AUC of 60.0%, 86.4%, and 0.79, respectively. The dual IF staining method using two combinations of MARS, AIMP2-DX2, and pan-CK is an effective diagnostic tool that can improve the lung cancer diagnostic yield by complementing conventional cytology.