Prognostic impact of miR-17-5p and miR-20a-5p in NSCLC diverge in subgroups according to lymph node status

Dagny Førde; Thomas Kilvær; Mona Irene Pedersen; Ana Paola Lombardi; Irene D'arsiè; Erna-Elise Paulsen; Lill-Tove Rasmussen Busund; Mehrdad Rakaee; Tom Dønnem; Sigve Andersen

doi:10.3389/fonc.2025.1606933

Prognostic impact of miR-17-5p and miR-20a-5p in NSCLC diverge in subgroups according to lymph node status

Front Oncol. 2025 Sep 25:15:1606933. doi: 10.3389/fonc.2025.1606933. eCollection 2025.

Authors

Dagny Førde¹, Thomas Kilvær^{1

2}, Mona Irene Pedersen¹, Ana Paola Lombardi³, Irene D'arsiè⁴, Erna-Elise Paulsen^{1

2}, Lill-Tove Rasmussen Busund^{3

5}, Mehrdad Rakaee^{3

5

6}, Tom Dønnem^{1

2}, Sigve Andersen^{1

2}

Affiliations

¹ Translational Cancer Research Group, Institute of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
² Department of Oncology, University Hospital of North Norway, Tromsø, Norway.
³ Translational Cancer Research Group, Institute of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway.
⁴ Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.
⁵ Department of Clinical Pathology, University Hospital of North Norway, Tromsø, Norway.
⁶ Department of Cancer Genetics, Oslo University Hospital, Oslo, Norway.

Abstract

Introduction: MicroRNAs (miRs) are short non-coding, functional RNA molecules that regulate gene expression. Different miRs are frequently dysregulated and implicated in the development and outcome of non-small cell lung cancer (NSCLC). We investigated the prognostic and functional aspects of miR-17-5p and miR-20a-5p by.

Methods: in situ hybridization in a large, well-characterized cohort of resected NSCLC patients and through overexpression in two NSCLC cell lines.

Results: In the overall cohort, we observed no prognostic impact of miR-17-5p and miR-20a-5p in univariate analyses, while high expression of miR-20a-5p was associated with a positive outcome in multivariate analyses (HR 0.732, 95% CI 0.544-0.986, p = 0.040). In subgroup analyses, high expression of miR-20a-5p was associated with a positive prognosis in patients with lung squamous cell carcinoma and lymph node metastases (N+). Interestingly, miR-17-5p was associated with a poor prognosis in patients without lymph node metastases (N0), while no prognostic impact was observed in N+ patients. In cell line studies, overexpression of miR-17-5p did not influence proliferation but led to increased invasion in both investigated cell lines. Overexpression of miR-20a-5p led to decreased proliferation in one of two investigated cell lines and, like miR-17-5p, increased invasion.

Discussion: Overall, our results suggest that the prognostic role of miR-17-5p and miR-20a-5p in early-stage NSCLC is context-dependent. Consequently, further studies are needed to elucidate the role of these miRs during NSCLC carcinogenesis. Clinical implementation should not be initiated until their role in different disease settings is sufficiently understood.

Keywords: NSCLC; cell lines; digital pathology; miR-17; miR-20; prognosis.