Worldwide, lung cancer is the most common form of cancer, with an estimated 2.09 million new cases and 1.76 million of death cause in 2018. It is categorized into two subtypes, small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). Although platinum-based chemotherapy or molecular targeted drugs is recommended for advanced stages of NSCLC patients, however, resistance to drug and chemotherapy are hindrances for patients to fully beneficial from these treatments. Clusterin (CLU), also known as apolipoprotein J, is a versatile chaperone molecule which produced by a wide array of tissues and found in most biologic fluids. There are studies reported high expression of CLU confers resistance to chemotherapy and radiotherapy in different lung cancer cell lines. By silencing CLU using Custirsen (OGX-011), a second-generation antisense oligonucleotide (ASO) that inhibits CLU production, not only could sensitized cells to chemo-and radiotherapy, also could decreased their metastatic potential. We will review here the extensive literature linking CLU to NSCLC, update the current state of research on CLU for better understanding of this unique protein and the development of more effective anti-CLU treatment.

Lung adenocarcinoma (LUAD) is one of the malignant tumors worldwide. The purpose of this study is to identify the hub genes related to LUAD using bioinformatics analysis. Three gene expression datasets (GSE27262, GSE74706, GSE75037) were obtained from GEO database. Identification of DEGs was performed using GEO2R and constructed protein-protein interaction network using STRING and cytoscape. GO, KEGG and GSEA analysis were carried out through R package “clusterprofiler”. GEPIA was used to verify the survival of hub genes, UALCAN database and HPA database were used to determine protein expression, complemented by IHC staining results. Lastly, CCK-8 and colony formation assays were used to verify PC9 cell growth ability and we used western blot, Transwell and scratch wound assays for validation of PC9 cells migration and EMT markers. We identified 107 up-regulated genes and 344 down-regulated genes. Thirty hub genes were identified and the 12 hub genes with a rank of degrees > 30 are as follow: CCNA2, AURKA, HMMR, EZH2, TTK, TPX2, CCNB1, ANLN, ECT2, CEP55, MAD2L1 and PBK. CCNA2 as one of the genes having the highest node degree of 35 was chosen for subsequent analysis. Our findings indicated that high expression of CCNA2 had the highest enrichment effects on cell cycle and was associated with poor prognosis. CCK-8 and colony formation analysis further verified that CCNA2 contributed to the progression of LUAD and the protein expression was significantly elevated in tumor tissues compared to the normal lung tissues. In addition, high expression of CCNA2 is related to the EMT process and may play a role in EMT-induced metastasis in LUAD. Briefly, CCNA2 was identified as one of the hub genes and can promote lung cancer cell growth, migration and invasion via epithelial-mesenchymal transition. Moreover, could avail as a biomarker or therapeutic target to judge the prognosis of LUAD.