Hypoxia contributes to the maintenance of stem-like cells in glioblastoma (GBM), and activates vascular mimicry and tumor resistance to anti-angiogenesis treatments. The present study examined the expression patterns and biological significance of hypoxia-inducible protein 2 (HIG2, also known as HILPDA) in GBM. HIG2 was highly expressed in gliomas and was correlated with tumor grade, and high HIG2 expression independently predicted poor GBM patient prognosis. HIG2 was upregulated during hypoxia and by hypoxia mimics, and HIG2 knockdown in GBM cells inhibited cell proliferation and invasion. HIF1α bound to the HIG2 promoter and increased its expression in GBM cells, and HIG2 upregulated HIF1α expression. Reconstruction of a HIG2-related molecular network using bioinformatics methods revealed that HIG2 is closely correlated with angiogenesis genes, such as VEGFA, in GBM. HIG2 levels positively correlated with VEGFA in GBM samples. In addition, treatment of transplanted xenograft nude mice with bevacizumab (anti-angiogenesis therapy) resulted in HIG2 upregulation at late stages. We conclude that HIG2 is overexpressed in GBM and upregulated by hypoxia, and is a potential novel therapeutic target. HIG2 overexpression is an independent prognostic indicator and may promote tumor resistance to anti-angiogenesis treatments.

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Crizotinib has achieved astonishing success in advanced non‐small‐cell lung cancer (NSCLC) patients harboring anaplastic lymphoma kinase (ALK) rearrangement. However, no real‐world studies described the clinicopathological characteristics and treatment of such patients in China. Patients were consecutively collected from Sun Yat‐sen University Cancer Center. Chi‐square test was applied to explore the relationship between ALK fusion status and metastasis sites. Kaplan–Meier methods and multivariable analyses were used to estimate progression‐free survival (PFS). A total of 291 advanced NSCLC patients (ALK (+), N = 97; both ALK & epidermal growth factor receptor (EGFR) (‐), N = 194) were enrolled. The occurrence of brain metastasis in ALK‐positive patients was significantly higher than double‐negative ones both at baseline (26.5% vs. 16.5%, P = 0.038) and during treatment (25.8% vs. 11.9%, P = 0.003), but opposite for pleural effusion (6.2% vs. 26.9%, P < 0.001 at baseline; 3.1% vs. 10.3%, P = 0.031 during treatment). ALK‐positive patients of 53.6% used crizotinib, whereas others only received chemotherapy (37.1%) or supportive care (9.3%). Usage of crizotinib prolonged PFS compared with chemotherapy in ALK‐positive patients (median PFS 17.6 m vs. 4.8 m, P < 0.001). ALK‐positive NSCLC had more brain metastasis and less pleural effusion than double‐negative ones. Crizotinib showed better PFS than chemotherapy in advanced ALK‐positive NSCLC at any line. However, half advanced ALK‐positive patients never received crizotinib, which was grim and need improving.