Insulin-Like Growth Factor 1 Receptor (IGF1R) Expression and Survival in Operable Squamous-Cell Laryngeal Cancer

Mountzios, Giannis; Kostopoulos, Ioannis; Kotoula, Vassiliki; Sfakianaki, Ioanna; Fountzilas, Elena; Markou, Konstantinos; Karasmanis, Ilias; Leva, Sofia; Angouridakis, Nikolaos; Vlachtsis, Konstantinos; Nikolaou, Angelos; Konstantinidis, Ioannis; Fountzilas, George

doi:10.1371/journal.pone.0054048

Cited by 40 publications

(35 citation statements)

References 32 publications

(50 reference statements)

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“…Other studies on cancer have revealed that the lack of correlation between mRNA and protein levels can be attributed to mRNA translational silencing, cleavage, or alternative splicing (Dziadziuszko et al 2010, Mountzios et al 2013. In the IGF1R context, alternative mRNA splicing can lead to distinct protein degradation rates in cancer cells (Mountzios et al 2013) while the frequently expressed isoform (alpha) of IGF1R is not directly associated with global IGF1R gene expression (Pollak 2012). Interestingly, reports have demonstrated the impact of IGF1R protein localization on the biological behavior and prognosis of human breast cancer and in clear renal cancer cells (Aleksic et al 2010, Tamimi et al 2011.…”

Section: Discussionmentioning

confidence: 99%

IGF2 and IGF1R in pediatric adrenocortical tumors: roles in metastasis and steroidogenesis

Lira¹,

Fedatto²,

Antônio³

et al. 2016

Endocrine-Related Cancer

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Deregulation of the IGF system observed in human tumors indicates a role in malignant cell transformation and in tumor cell proliferation. Although overexpression of the IGF2 and IGF1R genes was described in adrenocortical tumors (ACTs), few studies reported their profiles in pediatric ACTs. In this study, the IGF2 and IGF1R expression was evaluated by RT-qPCR according to the patient's clinical/pathological features in 60 pediatric ACT samples, and IGF1R protein was investigated in 45 samples by immunohistochemistry (IHC). Whole transcriptome and functional assays were conducted after IGF1R inhibition with OSI-906 in NCI-H295A cell line. Significant IGF2 overexpression was found in tumor samples when compared with non-neoplastic samples (P < 0.001), significantly higher levels of IGF1R in patients with relapse/metastasis (P = 0.031) and moderate/strong IGF1R immunostaining in 62.2% of ACTs, but no other relationship with patient survival and clinical/pathological features was observed. OSI-906 treatment downregulated genes associated with MAPK activity, induced limited reduction of cell viability and increased the apoptosis rate. After 24 h, the treatment also decreased the expression of genes related to the steroid biosynthetic process, the protein levels of the steroidogenic acute regulatory protein (STAR), and androgen secretion in cell medium, supporting the role of IGF1R in steroidogenesis of adrenocortical carcinoma cells. Our data showed that the IGF1R overexpression could be indicative of aggressive ACTs in children. However, in vitro treatments with high concentrations of OSI-906 (>1 μM) showed limited reduction of cell viability, suggesting that OSI-906 alone could not be a suitable therapy to abolish carcinoma cell growth. 23:6Research R C P Lira et al.IGF1R in pediatric adrenocortical tumor IGF2 and IGF1R in pediatric adrenocortical tumors: roles in metastasis and steroidogenesis

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Section: Discussionmentioning

confidence: 99%

IGF2 and IGF1R in pediatric adrenocortical tumors: roles in metastasis and steroidogenesis

Lira¹,

Fedatto²,

Antônio³

et al. 2016

Endocrine-Related Cancer

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“…The scoring of the staining pattern was based on the percentage of positive tumor cells: 0=0-5%, 1=6-25%, 2=26-50%, 3=51-100%). The localization of staining for each protein was also indicated either as cytoplasmic or cytoplasmic/membranous or membranous [14]. …”

Section: Methodsmentioning

confidence: 99%

“…In human cells, loss of IGF2R function has been associated with the development of cancers of the breast, lung, liver and ovary [12,13]. However, IGF2R expression was not associated with the clinical features of squamous-cell laryngeal cancer [14]. …”

Section: Introductionmentioning

confidence: 99%

IGF2R Expression is Associated with the Chemotherapy Response and Prognosis of Patients with Advanced NSCLC

Tian¹,

Yao²,

Song³

et al. 2014

Cell Physiol Biochem

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Background: Insulin-like growth factor (IGF) pathway has been suggested as a new molecular target for the treatment of cancer including Non-small cell lung cancer (NSCLC). We postulated that IGF-2 receptor (IGF2R) may be associated with treatment response and prognosis of NSCLC patients receiving chemotherapy. Methods: A total of 464 patients with inoperable advanced stage of NSCLC were enrolled. All patients received platinum-based chemotherapy. Meanwhile, the IGF2R expression in tumor samples was detected by Immunohistochemical analysis. The IGF2R expression was inhibited in several human NSCLC cell lines (H292, A549, NCI-H460, Calu-3 and NCI-H23) after small interfering RNA (siRNA) transfection and the cellular biology behavior were evaluated. Results: Of all NSCLC patients, 204 had high IGF2R expression and 260 had low IGF2R expression. The low IGF2R expression was significantly associated with the smoking status, higher tumor stage, and poorer differentiation status of these patients. Notably, we found that the low IGF2R expression was closely associated with the chemotherapy response in NSCLC patients. Patients with low IGF2R expressions had a poorer prognosis than those with high IGF2R expressions. IGF2R inhibition by si-RNA technique in NSCLC cell lines increased the proliferation, migration and invasion abilities, but reduced the apoptosis rate. IGF2R silencing significantly enhanced the chemo-resistance of NSCLC cell lines to cisplatin treatment. Conclusion: The IGF2R expression in tumor is associated with the chemotherapy response and prognosis of Patients with advanced NSCLC.

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“…Despite recent advances in multidisciplinary treatment strategies for LSCC, including targeted surgical extirpation or larynx-preservation protocols implementing chemotherapy or radiotherapy, a large proportion of patients with localized or advanced disease will eventually relapse and die. Indeed, the overall survival of LSCC has not improved much for years [5,6]. Therefore, identifying novel molecular indicators of its malignant behavior is of great interest and could be helpful for early prevention, diagnosis and treatment of LSCC.…”

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confidence: 99%

GROα expression and its prognostic implications in laryngeal squamous cell carcinoma

Liang¹,

Liu²,

Chen³

et al. 2015

neo

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The growth-regulated oncogene α (GROα) , which is also designated as CXC chemokine ligand 1 (CXCL1), was first identified as an autocrine growth factor in human malignant melanoma. It is involved in tumor development and invasion, and is highly expressed in various human cancers. However, little is known about the association between GROα expression and the clinical attributes of laryngeal squamous cell carcinoma (LSCC).One-step quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemical staining of tissue microarrays were employed to evaluate the relationship between GROα expression and LSCC clinicopathological attributes.GROα mRNA and protein expression levels were significantly greater in LSCC than in non-cancerous tumor-adjacent tissues. GROα protein expression in LSCC was also significantly associated with TNM stage, lymph node metastasis, and histopathological grade. Kaplan-Meier and Cox multi-factor analyses suggested that increased GROα expression and positive lymph node metastasis were significantly associated with the poor survival of LSCC patients.These data indicate that GROα may be a novel prognostic marker of LSCC.

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Insulin-Like Growth Factor 1 Receptor (IGF1R) Expression and Survival in Operable Squamous-Cell Laryngeal Cancer

Cited by 40 publications

References 32 publications

IGF2 and IGF1R in pediatric adrenocortical tumors: roles in metastasis and steroidogenesis

IGF2 and IGF1R in pediatric adrenocortical tumors: roles in metastasis and steroidogenesis

IGF2R Expression is Associated with the Chemotherapy Response and Prognosis of Patients with Advanced NSCLC

GROα expression and its prognostic implications in laryngeal squamous cell carcinoma

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