title: Co-expression of ILT4/HLA-G in human non-small cell lung cancer correlates with poor prognosis and ILT4-HLA-G interaction activates ERK signaling.
abstract: Non-small cell lung cancer (NSCLC) is the most common malignant tumor in the world, of which prognosis is generally poor due to insufficient mechanistic understanding. To explore the molecular pathogenesis of NSCLC, the co-expression of immunoglobulin-like transcript 4 (ILT4) and its ligand human leukocyte antigen G (HLA-G) in NSCLC tissues and cells were investigated. Here, we detected the expression of ILT4 and HLA-G in 81 tumor specimens from primary NSCLC patients, and we found that co-expression of ILT4/HLA-G was significantly associated with regional lymph node involvement, advanced stages, and the overall survival of patients. In NSCLC cell lines, HLA-G expression increased/decreased accordingly when ILT4 was up-/down-regulated, and ILT4 expression increased in a concentration-dependent manner via the stimulation of HLA-G fusion protein. Interestingly, HLA-G fusion protein could also up-regulate the phospho-ERK1/2 expression, which means the activation of extracellular signal-regulated kinase (ERK) signaling. All in all, our results indicate that the ILT4-HLA-G interaction might play an important role in NSCLC progression. Identification of ILT4 and HLA-G expression may provide an indicator to predict prognosis and guide prevention and treatment of NSCLC.
authors.affiliation: Department of Oncology, School of Medicine, Shandong University, 44 West Wenhua Road, Jinan, Shandong, 250012, People's Republic of China.|Department of Oncology, Jinan Central Hospital, Shandong University, 105 Jie Fang Road, Jinan, Shandong, 250013, People's Republic of China.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Jinan Central Hospital, Shandong University, 105 Jie Fang Road, Jinan, Shandong, 250013, People's Republic of China.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, Jinan Central Hospital, Shandong University, 105 Jie Fang Road, Jinan, Shandong, 250013, People's Republic of China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Oncology, Jinan Central Hospital, Shandong University, 105 Jie Fang Road, Jinan, Shandong, 250013, People's Republic of China.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Jinan Central Hospital, Shandong University, 105 Jie Fang Road, Jinan, Shandong, 250013, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Oncology, Jinan Central Hospital, Shandong University, 105 Jie Fang Road, Jinan, Shandong, 250013, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Oncology, Jinan Central Hospital, Shandong University, 105 Jie Fang Road, Jinan, Shandong, 250013, People's Republic of China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Oncology, Jinan Central Hospital, Shandong University, 105 Jie Fang Road, Jinan, Shandong, 250013, People's Republic of China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Oncology, Jinan Central Hospital, Shandong University, 105 Jie Fang Road, Jinan, Shandong, 250013, People's Republic of China.
authors.forename: Siyue
authors.initials: S
authors.lastname: Nie
authors.affiliation: Department of Oncology, Jinan Central Hospital, Shandong University, 105 Jie Fang Road, Jinan, Shandong, 250013, People's Republic of China. 13370582181@163.com.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D059951:HLA-G Antigens / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D020935:MAP Kinase Signaling System; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008875:Middle Aged; D011379:Prognosis; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D059951:HLA-G Antigens; C491341:LILRB2 protein, human; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic
keywords: Extracellular signal-regulated kinase; Human leukocyte antigen-G; Immunoglobulin-like transcript 4; Non-small cell lung cancer