Title:COL1A1 as a Potential Prognostic Marker and Therapeutic Target in
Non-small Cell Lung Cancer
Volume: 17
Issue: 10
Author(s): Boyu Pan, Chen Huang, Yafei Xia, Cuicui Zhang, Bole Li, Liangjiao Wang, Senbiao Fang, Liren Liu*Shu Yan*
Affiliation:
- Department of Gastrointestinal Cancer
Biology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer,
Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060,
China
- Tianjin Key Laboratory of Acute Abdomen Disease-associated Organ Injury and ITCWM Repair, ITCWM Hospital,
Tianjin University, No. 92 Weijin Road, Nankai District, Tianjin 300072, China
Keywords:
COL1A1, non-small cell lung cancer (NSCLC), chemosensitivity, bioinformatics analysis, differentially expressed genes (DEGs), prognosis.
Abstract:
Background: Nowadays, non-small cell lung cancer (NSCLC) is a common and highly fatal
malignancy worldwide. Therefore, identifying the potential prognostic markers and therapeutic targets is
urgent for patients.
Objective: This study aimed at finding hub targets associated with NSCLC using multiple databases.
Methods: Differentially expressed genes (DEGs) from Genome Expression Omnibus (GEO) cohorts
were employed for the enrichment analyses of Gene Ontology (GO) terms and the Kyoto Encyclopedia
of Genes and Genome (KEGG) pathways. Candidate key genes, filtered from the topological parameter
'Degree' and validated using the Cancer Genome Atlas (TCGA) cohort, were analyzed for their association
with clinicopathological features and prognosis of NSCLC. Meanwhile, immunohistochemical cohort
analyses and biological verification were further evaluated.
Results: A total of 146 DEGs were identified following data preprocessing, and a protein-protein interaction
(PPI) systematic network was constructed based on them. The top ten candidate core genes were
further extracted from the above PPI network by using 'Degree' value, among which COL1A1 was
shown to associate with overall survival (OS) of NSCLC as determined by using the Kaplan-Meier analysis
(p=0.028), and could serve as an independent prognostic factor for OS in NSCLC patients (HR,
0.814; 95% CI, 0.665-0.996; p=0.046). We then analyzed the clinical stages, PPI, mutations, potential
biological functions, and immune regulations of COL1A1 in NSCLC patients using multiple bioinformatics
tools, including GEPIA, GeneMANIA, cBioPortal, GESA, and TISIDB. Finally, we further experimentally
validated the overexpression of COL1A1 in NSCLC samples and found that inhibition of
COL1A1 expression moderately sensitized NSCLC cells to cisplatin.
Conclusion: Thus, our results showed that COL1A1 may serve as a potential prognostic marker and
therapeutic target in NSCLC.
