The Prognostic and Therapeutic Potential of LRIG3 and Soluble LRIG3 in Glioblastoma
Authors: Qungen Xiao
Dong Kuang
Qiuhong Duan
Dongsheng Guo
Heping Wang
Fangling Cheng
Minhai Dong
Po Zhang
Yue He
Feng Mao
Youwei Li
Baofeng Wang
Journal: Frontiers in Oncology (2019)
Discipline: CLINICAL MEDICINE
Keywords: LRIG3; MET/PI3K/Akt pathway; glioblastoma; glioma; prognosis
Affiliations: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Chinese-German Lab of Molecular Neuro-oncology of Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China., Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.

Abstract:  Glioblastoma is a highly lethal type of primary brain tumor that exhibits unrestricted growth and aggressive invasion capabilities, leading to a dismal prognosis despite a multitude of therapies. Multiple alterations in the expression level of genes and/or proteins have been identified in glioblastomas, including the activation of oncogenes and/or silencing of tumor-suppressor genes. Nevertheless, there are still no effective targeted therapies associated with these changes. In this study, we investigated the expression of human leucine-rich repeats and immunoglobulin-like domains protein 3 (LRIG3) in human glioma specimens through immunohistochemical analysis. The results showed that LRIG3 was weakly expressed in high-grade gliomas (WHO [World Health Organization] grades III and IV) compared with that in low-grade gliomas (WHO grade II). Survival analysis of these patients with glioma indicated that LRIG3 is an important prognostic marker for better survival. Moreover, we confirmed the existence of soluble ectodomain of LRIG3 (sLRIG3) in the cell culture supernatant, serum, and in tumor cystic fluid of patients with glioma. Molecular mechanistic investigation demonstrated that both LRIG3 and sLRIG3 inhibit the growth and invasion capabilities of GL15, U87, and PriGBM cells and tumor xenografts in nude mice through regulating the MET/phosphatidylinositol 3-kinase/Akt signaling pathway. Enzyme-linked immunosorbent assay confirmed the positive correlation between serum sLRIG3 protein levels and overall survival time in patients with high-grade gliomas. Taken together, our data for the first time demonstrate the existence of sLRIG3 and that both LRIG3 and sLRIG3 are potent tumor suppressors, which could be used as prognostic markers for better overall survival and therapeutic agents for glioblastoma. 

Retracted: No

PubPeer comments:
 Figure 4A has two duplicate panels.  , 
 Dear Capillacea, Thank you for pointing out our mistake. This is a mistake made when putting these pictures on a canvas for the first time. We are very sorry for the error. We already contacted the editors and sent the original data for the correction. This will make us pay more attention to the next article submission. Thank you again. Sincerely, Wang Baofeng , 
 Dear Capillacea, Thanks for your pointing out our mistake. This mistake was made during the first time putting these pictures together in one canvas. The picture in the third column of the first row was omitted owing to my carelessness. We have already contacted the editors and sent the original data for the correction and waiting for the reply to deal with this problem. Thank you again. Best regards, Cheng Fanglling Chengf , 
 Dear Capillacea, Thanks for your pointing out our mistake. This mistake was made during the first time putting these pictures together in one canvas. The picture in the third column of the first row was omitted owing to my carelessness. We have already contacted the editors and sent the original data for the correction and waiting for the reply to deal with this problem. Thank you again. Best regards, Cheng Fangling ,