# CLK1 is a potential tumor suppressor for NSCLC by regulating cell proliferation and immune infiltration

## TL;DR

CLK1 acts as a tumor suppressor in non-small cell lung cancer by reducing cell growth and boosting immune response, making it a promising target for treatment.

## Contribution

CLK1 is newly identified as a tumor suppressor in NSCLC, with roles in cell proliferation inhibition and immune infiltration.

## Key findings

- High CLK1 expression correlates with prolonged survival and suppressed cell cycle pathways in NSCLC.
- CLK1 overexpression inhibits cancer cell proliferation in vitro and is linked to increased CD4+ T cell infiltration.
- CLK1 is associated with higher tumor mutational burden and chemotherapy sensitivity in NSCLC patients.

## Abstract

Lung cancer is the malignancy with the highest global incidence and mortality. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of cases and is characterized by complex drug resistance and poor prognosis. While CLK1 has been implicated in Alzheimer’s disease, pancreatic cancer proliferation, and chemotherapy resistance in lymphoma, its role in NSCLC, particularly in the context of tumor immune infiltration, remains unexplored.

CLK1 expression and prognostic significance were analyzed across cancers and in LUAD using bioinformatics platforms (GEPIA, UALCAN). Functional enrichment analyses (GSEA, KEGG, GO) elucidated associated pathways and immune correlations. Drug sensitivity screening (GDSC, CTRP, CellMiner) identified potential compounds targeting CLK1-high tumors. Experimental validation was performed using clinical samples from NSCLC patients (n = 12) and in vitro assays with A549 and H1299 cell lines to assess CLK1 expression and its effect on proliferation.

Contrary to its oncogenic role in other cancers, CLK1 acts as a tumor suppressor in NSCLC. High CLK1 expression correlated with prolonged survival, suppressed cell cycle and metabolism pathways, and enhanced anti-tumor immunity—particularly CD4+ T cell infiltration. Clinically, high CLK1 was associated with increased tumor mutational burden and greater sensitivity to chemotherapy. Consistent with this, CLK1 was downregulated in NSCLC patient tissues of NSCLC, and its overexpression directly inhibits cancer cell proliferation in vitro.

Our findings demonstrate that CLK1 functions as a tumor suppressor gene in NSCLC, inhibiting proliferation and promoting immune infiltration. It also correlates positively with sensitivity to multiple chemotherapeutic agents. Thus, CLK1 may serve as a novel prognostic biomarker and a potential target for combination therapy in NSCLC.