Serum MALR Improves Diagnosis and Malignancy Assessment of Esophageal Cancer Among Patients With Esophageal Symptoms

Esophageal cancer (EC) shares symptoms with non-malignant esophageal diseases (NM-ED), and endoscopy is invasive and not always well tolerated, creating a need for blood-based markers in symptomatic patients. We enrolled 290 patients undergoing endoscopy for esophageal symptoms (180 EC and 110 NM-ED) and measured serum levels of six cancer-related long non-coding RNAs by quantitative PCR. MALR, HOXA10-AS, and LINC00324 were independently associated with EC after adjustment for clinical risk factors, with MALR showing the strongest effect (adjusted odds ratio per standard deviation 2.401, 95% CI 1.738–3.316). MALR alone yielded an area under the curve of 0.716. Adding MALR to a clinical model increased the area under the curve to 0.782 (ΔAUC 0.079, 95% CI 0.033–0.124) and significantly improved net reclassification improvement (0.626, 95% CI 0.403–0.850) and integrated discrimination improvement (0.112, 95% CI 0.076–0.148), whereas HOXA10-AS and LINC00324 provided limited incremental value. Higher MALR levels correlated with advanced TNM stage (R = 0.426), poorer differentiation (R = 0.454), and higher lymph node stage (R = 0.493). Serum MALR is a promising biomarker for distinguishing EC from NM-ED and may also reflect tumor aggressiveness in symptomatic patients.