Small RNA sequencing to differentiate lung squamous cell carcinomas from metastatic lung tumors from head and neck cancers

Yoshihisa Shimada; Jun Matsubayashi; Akira Saito; Tatsuo Ohira; Masahiko Kuroda; Norihiko Ikeda

doi:10.1371/journal.pone.0248206

Small RNA sequencing to differentiate lung squamous cell carcinomas from metastatic lung tumors from head and neck cancers

PLoS One. 2021 Mar 5;16(3):e0248206. doi: 10.1371/journal.pone.0248206. eCollection 2021.

Authors

Yoshihisa Shimada¹, Jun Matsubayashi², Akira Saito³, Tatsuo Ohira¹, Masahiko Kuroda³, Norihiko Ikeda¹

Affiliations

¹ Department of Thoracic Surgery, Tokyo Medical University, Tokyo, Japan.
² Department of Anatomical Pathology, Tokyo Medical University, Tokyo, Japan.
³ Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Circulating MicroRNA* / blood
Circulating MicroRNA* / genetics
Female
Head and Neck Neoplasms* / blood
Head and Neck Neoplasms* / classification
Head and Neck Neoplasms* / genetics
Humans
Lung Neoplasms* / blood
Lung Neoplasms* / classification
Lung Neoplasms* / genetics
Male
RNA, Neoplasm* / blood
RNA, Neoplasm* / genetics
RNA-Seq*
Squamous Cell Carcinoma of Head and Neck* / blood
Squamous Cell Carcinoma of Head and Neck* / classification
Squamous Cell Carcinoma of Head and Neck* / genetics

Substances

Circulating MicroRNA
RNA, Neoplasm

Grants and funding

This study was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Education, Culture, Sports, and Technology, Japan (#18K08799; Y. Shimada), and internal research funding from department of thoracic surgery, Tokyo Medical University. There was no additional external funding received for this study.