Abstract
Distinguishing lung squamous cell carcinoma (LSQCC) from a solitary metastatic lung tumor (MSQCC) from head and neck squamous cell carcinoma (HNSQCC) presents a difficult diagnostic challenge even after detailed pathological assessment. Treatment options and estimated survival outcomes after pulmonary resection differ between patients with LSQCC and MSQCC. This study aimed to investigate whether microRNA (miRNA) profiling by RNA sequencing of HNSQCC, MSQCC, and LSQCC was useful for differential diagnosis of MSQCC and LSQCC. RNA sequencing was performed to identify bioinformatically significant miRNAs from a formalin-fixed paraffin-embedded (FFPE) block from a derivation set. MiRNA levels were confirmed by validation sets using FFPE samples and serum extracellular vesicles from patients. Step-wise discriminant analysis and canonical discriminant analysis identified 13 miRNAs by which the different expression patterns of LSQCC, MSQCC, and HNSQCC groups were demonstrated. Six miRNAs (miR-10a/28/141/320b/3120) were assessed in validation sets, and 4 miRNAs (miR-10a/28/141/3120) were significantly upregulated in LSQCCs compared with MSQCCs and HNSQCCs. Serum extracellular vesicles from LSQCC patients demonstrated significantly elevated miR-10a (p = .042), miR-28 (p = .041), and miR-3120 (p = .047) levels compared with those from MSQCC patients. RNA sequencing is useful for differential diagnosis of LSQCC and MSQCC, and the expression level of miR-10a, miR-28, and miR-3120 in serum extracellular vesicles are promising noninvasive tools for this purpose.
Highlights
Smoking acts as a significant risk factor for lung squamous cell carcinoma (LSQCC) and head and neck squamous cell carcinoma (HNSQCC)
We reveal 2 representative Venn diagrams of a patient with LSQCC with a past treatment history of HNSQCC, and the other patient with MSQCC with a history of HNSQCC
When a pure-solid pulmonary nodule detected in patients with a history of HNSQCC, a differential diagnosis must be made between metastasis and primary lung cancer
Summary
Smoking acts as a significant risk factor for lung squamous cell carcinoma (LSQCC) and head and neck squamous cell carcinoma (HNSQCC). The patient’s clinical profiles and the histological appearance of both tumors are similar [1]. As it is often shown for both tumors to arise in the same patient, distinguishing an independent LSQCC from a solitary metastatic lung tumor. Small-seq in squamous cell cancer in the lung
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