Insulin-like growth factor II mRNA-binding protein 3 expression promotes tumor formation and invasion and predicts poor prognosis in oral squamous cell carcinoma

Lin, Chiao Ying; Chen, Szu-Ta; Jeng, Yung‐Ming; Yeh, Cheng Chang; Chou, Han Yi; Deng, Yi; Chang, Cheng; Kuo, Mark Yen‐Ping

doi:10.1111/j.1600-0714.2011.01019.x

Cited by 29 publications

(34 citation statements)

References 25 publications

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“…The 53 studies involved 8,937 patients with different cancer types, including 6 studies of RCC,8,25–29 6 lung cancer,9,30–34 4 oral cancer,10,35–37 4 urothelial carcinoma,38–41 4 ovarian cancer,16,17,42,43 3 hepatocellular carcinoma (HCC),44–46 4 colorectal cancer,12,47–49 3 prostate cancer,14,15,50 3 pancreatic cancer,51–53 2 gastric cancer,11,54 2 intrahepatic cholangiocarcinoma (ICC),55,56 and one study each of tongue cancer,57 thyroid carcinoma,58 sacral chordoma,59 pilocytic astrocytoma and pilomyxoid astrocytoma (PA/PMA),60 neuroblastoma,61 meningioma,62 melanoma,63 breast cancer,64 giant cell tumor,65 bile duct carcinoma,66 esophageal carcinoma,67 and cervical cancer 13. A total of 25 studies involved Caucasians and 28 involved Asians.…”

Section: Resultsmentioning

confidence: 99%

Prognostic value of high IMP3 expression in solid tumors: a meta-analysis

Chen¹,

Xie²,

Li³

et al. 2017

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BackgroundAccumulated studies have investigated the prognostic role of insulin-like growth factor II mRNA-binding protein 3 (IMP3) in various cancers, but inconsistent and controversial results were obtained. Therefore, we performed a systematic review and meta-analysis to investigate the potential value of IMP3 in the prognostic prediction of human solid tumors.Materials and methodsA systematic literature search in the electronic databases PubMed, Embase, Web of Science, and Cochrane library (updated to April 2016) was conducted to identify eligible studies. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for survival outcomes were calculated and gathered using STATA 12.0 software.ResultsA total of 53 studies containing 8,937 patients with solid tumors were included in this meta-analysis. High IMP3 expression was significantly associated with worse overall survival (OS) of solid tumors (HR =2.08, 95% CI: 1.80–2.42, P<0.001). Similar results were observed in cancer-specific survival (CSS), disease-free survival (DFS), recurrence-free survival (RFS), progression-free survival (PFS), and metastasis-free survival (MFS). Further subgroup analysis stratified by tumor type showed that elevated IMP3 expression was associated with poor OS in renal cell carcinoma (RCC), lung cancer, oral cancer, urothelial carcinoma, hepatocellular carcinoma (HCC), colorectal cancer, pancreatic cancer, gastric cancer, and intrahepatic cholangiocarcinoma (ICC).ConclusionThe current evidence suggests that high IMP3 expression is associated with poor prognosis in most solid tumors. IMP3 is a potential valuable prognostic factor and might serve as a promising biomarker to guide clinical decisions in human solid tumors.

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Section: Resultsmentioning

confidence: 99%

Prognostic value of high IMP3 expression in solid tumors: a meta-analysis

Chen¹,

Xie²,

Li³

et al. 2017

OTT

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“…Although extensively studied in several cancer types, only a few studies have previously investigated the expression status of IMP3 in HNSCC. IMP3 overexpression in SCC of the oral cavity was shown to be an independent predictive marker for an advanced clinical stage, lymph node metastasis and as a prognostic indicator (29)(30)(31). Furthermore, it has been reported to be an indicator of a poor prognosis and a marker of enhanced malignancy in SCC of the tongue and larynx (32)(33)(34)(35).…”

Section: Discussionmentioning

confidence: 96%

“…However, only a few studies have previously investigated the expression of IMP3 in head and neck SCC from specific sites (29)(30)(31)(32)(33)(34). In particular, the pattern of IMP3 expression in HNSCC with regards to the HPV status has not previously been investigated.…”

Section: Introductionmentioning

confidence: 99%

IMP3 and p16 expression in squamous cell carcinoma of the head and neck: A comparative immunohistochemical analysis

et al. 2017

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Abstract. Expression of p16 has been established as a good surrogate marker for high-risk human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC) patients, and it has been associated with an improved prognosis, irrespective of the actual HPV status. Conversely, the human insulin-like growth factor II mRNA binding protein 3 (IMP3) has been related to aggressiveness in several types of tumors. The aim of the present study was to investigate and compare p16 and IMP3 as markers of favorable and unfavorable behavior, respectively, in head and neck SCC (HNSCC), with particular reference to the HPV status. Both markers were analyzed by immunohistochemical analysis of 156 HNSCC samples originating from the oropharynx (n=81), oral cavity (n=44), larynx (n=15), hypopharynx (n=10) and nasopharynx (n=6). The HPV status was examined in a randomly selected representative subcohort (n=38) using polymerase chain reaction. Of the 156 HNSCC samples, 81 (51.9%) and 54 (34.6%) were positive for IMP3 and p16, respectively. IMP3 expression (P=0.022), p16 expression (P<0.001) and the combination of these markers (P<0.001) were significantly associated with tumor site. In particular, 69/81 (85%) OPSCC samples were positive for either one or both markers compared with 36/75 (48%) SCC samples from other sites. p16 expression was significantly associated with HPV infection (P= 0.017) and a trend towards a negative association between IMP3 expression and HPV infection was observed (P=0.053). The results of the present study suggested that IMP3 and p16 are more frequently expressed in OPSCC compared with other HNSCCs. The prognostic impact of IMP3 on OPSCC remains to be investigated in a larger series with an extended follow-up period. IntroductionSquamous cell carcinoma (SCC) is the leading cancer type affecting the head and neck region (HNSCC) representing >90% of malignant neoplasms of the oral cavity and oropharynx and 5 and 2% of all cancers in men and women, respectively (1). Tobacco smoking and alcohol consumption are the two major etiological factors of HNSCC and they work in a synergistic manner to initiate SCC (1). Approximately 75% of HNSCC cases in western countries are related to these two major risk factors, while the remainder is predominantly associated with viral infection, in particular infection with high-risk human papillomavirus (HPV) (1). HPV has been detected in a small fraction of oral cavity SCCs, and in 40-50% of oropharyngeal (mainly tonsillar) SCC (OPSCC) (1). While HPV-associated HNSCC may occur at any site, including the sinonasal tract, the majority of HPV-related SCCs originate in the lymphoid tissue bearing the oropharynx, mainly the palatine tonsil and the base of the tongue (1). Expression of p16 as a consequence of oncogenic HPV infection has been increasingly used as a surrogate marker for high-risk HPV infection, particularly in the female genital tract and the oropharynx (2,3). The sensitivity and specificity of p16 immunostaining for detecting high-risk HPV in OPSCC patie...

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“…IGF2BP proteins are also known to be associated with cancer metastasis and expression of classical oncogenes such as MYC and KRAS . Expression of IGF2BP3 in HNSCC and its role in tumor progression has been established . We report here for the first time the overexpression of HMGB2 in association with HNSCC.…”

Section: Resultsmentioning

confidence: 71%

Silencing of high‐mobility group box 2 (HMGB2) modulates cisplatin and 5‐fluorouracil sensitivity in head and neck squamous cell carcinoma

et al. 2015

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Dysregulation of protein expression is associated with most diseases including cancer. Mass spectrometry-based proteomic analysis is widely employed as a tool to study protein dysregulation in cancers. Proteins which are differentially expressed in head and neck squamous cell carcinoma (HNSCC) cell lines compared to the normal oral cell line could serve as biomarkers for patient stratification. To understand the proteomic complexity in HNSCC, we carried out iTRAQ-based mass spectrometry analysis on a panel of HNSCC cell lines in addition to a normal oral keratinocyte cell line. LC-MS/MS analysis of total proteome of the HNSCC cell lines led to the identification of 3,263 proteins, of which 185 proteins were overexpressed and 190 proteins were downregulated more than 2-fold in at least two of the three HNSCC cell lines studied. Amongst the overexpressed proteins, 23 proteins were related to DNA replication and repair. These included high mobility group box 2 (HMGB2) protein, which was overexpressed in all three HNSCC lines studied. Overexpression of HMGB2 has been reported in various cancers, yet its role in HNSCC remains unclear. Immunohistochemical labeling of HMGB2 in a panel of HNSCC tumors using tissue microarrays revealed overexpression in 77% (54 of 70) of tumors. The HMGB proteins are known to bind to DNA structure resulting from cisplatin-DNA adducts and affect the chemosensitivity of cells. We observed that siRNA-mediated silencing of HMGB2 increased the sensitivity of the HNSCC cell lines to cisplatin and 5-FU. We hypothesize that targeting HMGB2 could enhance the efficacy of existing chemotherapeutic regimens for treatment of HNSCC.

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Insulin-like growth factor II mRNA-binding protein 3 expression promotes tumor formation and invasion and predicts poor prognosis in oral squamous cell carcinoma

Abstract: IGF2BP3 enhances cell invasion ability and tumorigenicity in human OSCC in vitro and in vivo. IGF2BP3 is an independent prognostic factor in patients with OSCC. Targeting of IGF2BP3 could potentially suppress the tumor growth and metastasis to improve the outcome of patients with OSCC.

Cited by 29 publications

References 25 publications

Prognostic value of high IMP3 expression in solid tumors: a meta-analysis

Prognostic value of high IMP3 expression in solid tumors: a meta-analysis

IMP3 and p16 expression in squamous cell carcinoma of the head and neck: A comparative immunohistochemical analysis

Silencing of high‐mobility group box 2 (HMGB2) modulates cisplatin and 5‐fluorouracil sensitivity in head and neck squamous cell carcinoma

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