A 3′-Untranslated Region Polymorphism in <i>IGF1</i> Predicts Survival of Non–Small Cell Lung Cancer in a Chinese Population

Zhang, Mingfeng; Hu, Zhibin; Huang, Jinlin; Shu, Yongqian; Dai, Juncheng; Jin, Guangfu; Tang, Rong; Dong, Jingjing; Chen, Yijiang; Xu, Lin; Huang, Xin-En; Shen, Hongbing

doi:10.1158/1078-0432.ccr-09-2719

Cited by 38 publications

(37 citation statements)

References 40 publications

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“…IGF1 is a cancer progression-related gene that is associated with the growth, metastasis and chemoresistance of various cancers (23)(24)(25)(26)(27). In the present study, we confirmed that TAMs significantly expressed higher IGF1 levels than M0 cells as (Fig.…”

Section: Discussionsupporting

confidence: 83%

“…This pathway can enhance the proliferation and development of cells by initiating the anti-apoptotic PI3K/Akt/mTOR and the mitogenic Ras/Raf/Mek/Erk pathways (21,22). The IGF1 pathway is associated with the growth, metastasis and clinical outcome of various cancers, including prostate cancer, gastric cancer, lung cancer and breast cancer (23)(24)(25)(26)(27). For example, CAFs can increase the invasion ability of pancreatic cancer cells via paracrine IGF1/ IGF1R signaling, particularly under hypoxia (27), and IGF1R is highly expressed in chronic lymphocytic leukemia cells, whereas the inhibition of IGF1R can enhance the death of CLL cells (28).…”

Section: Introductionmentioning

confidence: 99%

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Upregulation of IGF1 by tumor-associated macrophages promotes the proliferation and migration of epithelial ovarian cancer cells

Liu

Wang

et al. 2017

Oncol Rep

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Abstract. Ovarian cancer (OC), of which epithelial ovarian cancer (EOC) is the most common, is the deadliest gynecological tumor because of the difficulties in detection at early stages, and metastasis and chemoresistance at advanced stages. Tumor-associated macrophages (TAMs) differentiate through alternative pathways and play important roles in tumor growth and metastasis. However, the underlying mechanism remains unclear. Here, we established a mouse TAM model using bone marrow monocytes and conditioned medium (CM) of TAMs to culture ID8 mouse EOC cells. The results showed that TAM CM accelerated the proliferation and migration of ID8 cells. In a previous study, gene chip analysis showed that human TAMs expressed significantly higher levels of insulinlike growth factor-1 (IGF1) than undifferentiated M0 myeloid cells. In the present study, we observed that the IGF1 level was higher in human EOC specimens than that in benign ovarian tumor specimens, and further analysis showed that a higher level of IGF1 was related to more advanced clinical stage and liver metastasis. Therefore, we hypothesized that TAMs may accelerate the proliferation and migration of EOC cells by upregulating IGF1. As expected, increased IGF1 expression at both the mRNA and protein levels was observed in ID8 cells cultured with TAM CM, whereas blockade of the IGF1 pathway in ID8 cells with an IGF1 neutralizing antibody effectively reversed the promotion of proliferation and migration. Finally, we inhibited the phosphorylation of insulin-like growth factor-1 receptor (IGF1R) and its downstream molecules Akt and Erk with the IGF1R inhibitor linsitinib, and observed that the treatment effectively suppressed the proliferation and migration of ID8 cells exposed to TAM CM. Thus, we demonstrated that TAMs may promote the growth and metastasis of EOC via the activation of the IGF1 pathway; thus, targeting the IGF1 pathway may be promising for EOC therapy.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Upregulation of IGF1 by tumor-associated macrophages promotes the proliferation and migration of epithelial ovarian cancer cells

Liu

Wang

et al. 2017

Oncol Rep

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“…Genetic factors could influence circulating IGF1 concentration [24]. Nowadays, multiple studies in many places have reported the associations between IGF1 polymorphisms and various cancers [25,26,27,28,29,30,31]. However, there have been no studies to investigate the IGF1 polymorphism and risk of childhood ALL.…”

Section: Introductionmentioning

confidence: 99%

Interaction Between IGF1 Polymorphisms and the Risk of Acute Lymphoblastic Leukemia in Chinese Children

Lu¹,

Wang²,

He³

et al. 2015

Cell Physiol Biochem

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Background/Aims: IGF1 is a key regulator in cell proliferation and apoptosis, and the 3' un-translated region (3'UTR) of the gene plays an important role in gene expression. For the first time, we explored the relationship between polymorphisms in the IGF1 3'UTR region and the risk of childhood acute lymphoblastic leukemia (ALL). Methods: Questionnaires were applied to collect epidemiological data. The genotypes of IGF1 polymorphisms were tested in a population of 744 ALL patients and 1088 cancer-free controls utilizing Taqman. Cell functional studies included real-time PCR, cell culture and transfection and luciferase assays. Results: We found that rs6214 homozygous AA genotype and rs6218 homozygous CC genotype were significantly associated with increased risk of childhood ALL. In addition, rs6218 CC genotype was associated with increased level of IGF1 mRNA in bone marrow, and the mutation in rs6218 led to aberrant binding capacity of hsa-miR-603 and hsa-miR-3941 in the 3'UTR of IGF1. Conclusion: Polymorphisms of rs6214 and rs6218 in the 3'UTR of IGF1 are associated with childhood ALL susceptibility, and the polymorphism of rs6218 is related with IGF1 expression at mRNA level.

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“…The patients' enrollment was described previously [21] . Patients were recruited from Jiangsu Cancer Hospital and the First Affiliated Hospital of Nanjing Medical University, Nanjing, China, from July 2003 to April 2008.…”

Section: Study Populationmentioning

confidence: 99%

“…The demographic characteristics and clinical features of the 568 NSCLC patients have been described previously [21] . No significant associations were observed between survival and patients' characteristics (i.e., smoking status, histological type, chemotherapy or radiation treatment), except for clinical stage (Log-rank P<0.001) and surgical operation (Log-rank P<0.001).…”

Section: Study Populationmentioning

confidence: 99%

Plasma vitamin D levels and vitamin D receptor polymorphisms are associated with survival of non-small cell lung cancer

Liu

Chen

et al. 2011

Chin. J. Cancer Res.

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Objective: Vitamin D and its receptor (VDR) involve in multiple cellular processes and play an important role in the initiation and progression of malignancy. Thus we hypothesized that plasma vitamin D levels and single nucleotide polymorphisms (SNPs) in VDR may be of prognostic significance in non-small cell lung cancer (NSCLC).Methods: We examined plasma 25-hydroxyvitamin D [25(OH)D] levels in 87 patients diagnosed with NSCLC using enzyme-linked immunosorbent assay (ELISA) and genotyped seven potentially functional SNPs in VDR in 568 NSCLC patients on Illumina Golden Gate platform.Results: Patients with higher plasma 25(OH)D levels had worse survival than patients with lower ones (P for trend = 0.048). The SNPs of rs1544410 and rs739837 were independently associated with NSCLC survival (adjusted HR = 1.61, 95% CIs = 1.06-2.45 for rs739837 AA vs AC/CC and adjusted HR = 1.51, 95% CIs = 1.06-2.16 for rs1544410 AG/AA vs GG). A joint effect was observed between rs1544410 and rs739837 and the risk of death elevated as the number of unfavourable genotypes patients carried increased (P for trend = 0.003). There were no significant associations between VDR polymorphisms and plasma 25(OH)D levels.Conclusion: Our findings indicate that plasma 25(OH)D levels and genetic variants of VDR may serve as prognostic markers for NSCLC in this Chinese population.

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A 3′-Untranslated Region Polymorphism in IGF1 Predicts Survival of Non–Small Cell Lung Cancer in a Chinese Population

Cited by 38 publications

References 40 publications

Upregulation of IGF1 by tumor-associated macrophages promotes the proliferation and migration of epithelial ovarian cancer cells

Upregulation of IGF1 by tumor-associated macrophages promotes the proliferation and migration of epithelial ovarian cancer cells

Interaction Between IGF1 Polymorphisms and the Risk of Acute Lymphoblastic Leukemia in Chinese Children

Plasma vitamin D levels and vitamin D receptor polymorphisms are associated with survival of non-small cell lung cancer

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