Predictive value of peripheral blood hsa-miR-122-5p and hsa-miR-486-5p for response to neoadjuvant chemoimmunotherapy in lung squamous cell carcinoma

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OBJECTIVE: To evaluate the predictive value of peripheral blood microRNAs for response to neoadjuvant chemoimmunotherapy in resectable lung squamous cell carcinoma. METHODS: Fifteen patients with resectable lung squamous cell carcinoma who received neoadjuvant chemoimmunotherapy followed by surgery between October 2020 and June 2021 were prospectively enrolled, together with 4 healthy volunteers. Plasma samples were collected before and after treatment for microRNA sequencing. Pathological response was assessed by experienced pathologists, and patients were classified as pathological complete response or non-pathological complete response. Differentially expressed microRNAs were identified using edgeR, and their associations with tumor burden, treatment response, and treatment-related changes were analyzed. RESULTS: Sixteen microRNAs showed at least 2-fold differential expression in patients compared with healthy volunteers. Among these, hsa-miR-122-5p and hsa-miR-486-5p were associated with tumor burden. hsa-miR-122-5p expression was 4.49-fold higher in T1-2 than in T3-4 disease and 2.25-fold higher in N0-1 than in N2 disease. In contrast, hsa-miR-486-5p expression was 1.40-fold higher in T3-4 than in T1-2 disease and was not associated with nodal stage. Baseline hsa-miR-122-5p was 2.39-fold higher in patients who achieved pathological complete response, whereas baseline hsa-miR-486-5p was 1.76-fold higher in patients without pathological complete response. After treatment, both microRNAs increased significantly in patients with pathological complete response and in those with nodal downstaging, but not in non-responders. CONCLUSIONS: Peripheral blood hsa-miR-122-5p and hsa-miR-486-5p were associated with tumor burden and treatment response in resectable lung squamous cell carcinoma. Baseline expression and on-treatment changes of these microRNAs may serve as noninvasive biomarkers for response to neoadjuvant chemoimmunotherapy.

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