Title:Expression and Predictive Significance of FHL1 and SLIT3 in Surgically
Resected Lung Adenocarcinoma
Volume: 26
Issue: 12
Author(s): Jinjing Song, Kai Liang, Tongtong Wei, Li Li, Zhiguang Huang, Gang Chen, Naiquan Mao*Jie Yang*
Affiliation:
- Department of Thoracic Tumor Surgery, The Affiliated Cancer Hospital of Guangxi Medical University,
Nanning 530021, Guangxi, People’s Republic of China
- Department of Pharmacology, School of Pharmacy, Guangxi Medical University, Nanning 530021, Guangxi, People’s
Republic of China
Keywords:
Lung adenocarcinoma, RNA sequencing, differentially expressed genes, prognosis, surgery, clinical specimen.
Abstract:
Objective: Lung adenocarcinoma (LUAD) is the most common type of lung cancer.
However, predictive biomarkers for early efficacy and prognosis evaluation in patients with surgically
resected LUAD are not completely explained.
Methods: Differentially expressed genes (DEGs), gene ontology (GO) and Kyoto Encyclopedia of
Genes and Genomes (KEGG) were identified by RNA sequencing (RNA-Seq) between thirteen
LUAD tissues and five normal lung tissues. The expression of DEGs was confirmed by qRT-PCR
and a validated cohort from GEPIA. Protein-protein interaction (PPI) network of the top 5% DEGs
was constructed by STRING and visualized in Cytoscape. Immunofluorescence results were acquired
from clinical specimens from LUAD patients. The expression of FHL1 was analyzed by
ImageJ. Survival analysis was performed using the GEPIA dataset.
Results: Consistent with the RNA-Seq data, validation of DEGs expression by qRT-PCR and GEPIA
cohort showed that FHL1 and SLIT3 were down-regulated in LUAD patient tissues compared
with non-tumor tissues. Moreover, FHL1 was significantly reduced in LUAD cell lines compared
to the bronchial epithelium cell line (P < 0.01). However, SLIT3 was elevated in A549 and H1299
cells (wide type EGFR) (P < 0.05) while decreased in HCC827 and PC9 cells (mutant EGFR)
compared to BESA-2B cells (P < 0.01). PPI network revealed the most significant cluster with 10
nodes and 43 edges. Immunofluorescent staining also showed that the expression of FHL1 was
lower in LUAD tissues compared with that in normal lung tissues (P < 0.01). The expressions of
SLIT3 and FHL1 were positively correlated. Specifically, the higher expression level of SLIT3 and
FHL1 independently predicted a better prognosis (P < 0.01 or P < 0.05).
Conclusion: Our findings provide two novel candidates, FHL1 and SLIT3, for prognostic evaluation
and treatments after surgery.