Abstract
Abstract Objective Ferroptosis is a type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides, which was involved in the progression of malignant tumors including non-small cell lung cancer (NSCLC). Material/methods Ferroptosis inhibiting gene solute carrier family 7 member 11 (SLC7A11) mRNA expression was investigated in the database of TCGA and Oncomine and compared between the cancer tissue and the normal corresponding tissue of NSCLC patients. SLC7A11 gene mutation of NSCLC was investigated in the TCGA database by the online data analysis tool of Catalog of Somatic Mutations in Cancer (COSMIC) and cBioPortal. The protein–protein interaction (PPI) network of SLC7A11 and associated genes were constructed with the STRING database. Gene ontology (GO) and the KEGG pathway of genes involved in the PPI network were explored and demonstrated by a bubble plot. Progression-free survival (PFS), overall survival (OS) and postprogression survival (PPS) between SLC7A11high and SLC7A11low expression groups were compared and demonstrated by the survival curve. Results SLC7A11 mRNA was upregulated in cancer tissues compared to paired normal tissues in colorectal adenocarcinoma, esophageal squamous cell carcinoma, lung squamous cell carcinoma rectum adenocarcinoma and uterine corpus endometrial carcinoma. Missense and synonymous substitutions were 66.67% and 16.67% for lung squamous cell carcinoma. For lung adenocarcinoma, the missense and synonymous substitutions were 66.67% and 33.33% respectively. In the case of single nucleotide mutation, A>T, C>G, G>A, G>T for lung squamous cell carcinoma and G>T, C>A, G>A, T> for lung adenocarcinoma were the most common mutations in the SLC7A11 coding strand. Fifty-one genes were included in the PPI network with an edge number of 287, average node degree of 11.3 and local clustering coefficient of 0.694, which demonstrated that the PPI network was enriched significantly (p = 1.0 × 10−16). In terms of the KEGG pathway, the SLC7A11 and PPI-involved genes were mainly enriched in ferroptosis, NSCLC, pathways in cancer, tp53 signaling pathway, etc. The overall survival (OS) in the SLC7A11high group was significantly lower than those of SLC7A11low groups in NSCLC (HR = 1.15, 95% CI: 1.02–1.31, p = 0.027). However, the progression-free survival (PFS) (HR = 1.17, 95% CI: 0.97–1.42, p = 0.098) and postprogression survival (PPS) (HR = 1.00, 95% CI: 0.78–1.29, p = 0.97) between SLC7A11high and SLC7A11low expression groups were not statistically different. Conclusion SLC7A11 was upregulated in NSCLC and correlated with the patient’s poor overall survival. SLC7A11 may be a potential target for NSCLC treatment through the ferroptosis pathway.
Highlights
It has been reported that 2.1 million newly diagnosed lung carcinoma and 1.8 million lung cancer deaths cases were identified in the year 2018, which take part in nearly 1 in 5 (18.4%) of all malignant carcinoma caused death [1]
SLC7A11 is a key gene in the pathway of ferroptosis, which was generally upregulated in cancer cells and promoted cancer cells growth partly by suppressing ferroptosis, a form of regulated cell death induced by excessive lipid peroxidation [15]
Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment indicated that SLC7A11- and protein–protein interaction (PPI)-involved genes were mainly enriched in ferroptosis, non-small cell lung cancer (NSCLC), pathways in cancer and the p53 signaling pathway
Summary
It has been reported that 2.1 million newly diagnosed lung carcinoma and 1.8 million lung cancer deaths cases were identified in the year 2018, which take part in nearly 1 in 5 (18.4%) of all malignant carcinoma caused death [1]. Ferroptosis-associated gene SLC7A11 is upregulated in NSCLC 107. Years, with the rapid development of tumor molecular biology technology and relevant cancer databases, the lung cancer diagnosis, prognosis and targeted therapy had been improved especially for advanced cases [2,3,4,5]. A new cell death pathway, named ferroptosis, a form of regulated cell death induced by excessive lipid peroxidation was first reported by Dixon et al [6]. It had been reported that solute carrier family 7 member 11 (SLC7A11) was upregulated in multiple cancers and can activate cancer cell growth by inhibiting ferroptosis [11,12,13]. We investigate SLC7A11 gene expression and its prognosis for NSCLC by using the relevant databases
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