The implication of osteopontin (OPN) expression and genetic polymorphisms of OPN promoter in oral carcinogenesis

Chiu, Yu‐Wei; Tu, Hsi-Feng; Wang, I-Kai; Wu, Cheng‐Hsien; Chang, Kuo‐Wei; Liu, Tsung‐Yun; Kao, Shou Yen

doi:10.1016/j.oraloncology.2010.01.018

Cited by 36 publications

(38 citation statements)

References 24 publications

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“…The authors found that the -443CC genotype had higher levels of OPN mRNA compared with other allelic variants and -443C>T variants might influence the OPN mRNA levels via binding of c-Myb transcription factor [45]. In oral squamous cell carcinoma (OSCC) patients, the -443 T/T genotype was found to be more prevalent in OSCC patients [25]. Our data showed that the only genotype of -443C>T were significantly related to the PTC risk, rather than the other two.…”

Section: Discussionmentioning

confidence: 99%

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OPN -443C>T Genetic Polymorphism and Tumor OPN Expression are Associated with the Risk and Clinical Features of Papillary Thyroid Cancer in a Chinese Cohort

Wang

Cai

et al. 2013

Cell Physiol Biochem

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Aim: to test the possible association between the polymorphism of Osteopontin (OPN) gene with the risk and the clinical features of papillary thyroid cancer (PTC). Methods: A total of 363 PTC patients and 413 healthy controls were enrolled. OPN expressions in tumor tissue were detected by immunohistochemistry. OPN gene polymorphisms, namely, -66T>G (rs28357094), -156G>GG (rs17524488), and -443C>T (rs11730582), were determined. Results: We observed that the PTC patients had significantly higher rates of -443TT genotypes than controls (P<0.001). The multivariate logistic regression analysis showed a significantly increased risk for PTC for the -443CC genotype compared with the -443TT genotype (adjusted OR= 4.312, 95%CI: 2.747 -6.987, adjusted P < 0.001). OPN protein was not expressed in normal thyroid tissues while tumor samples from PTC patients were shown to have high expressions of OPN. Also, we found that the high OPN expressions were significantly more prevalent in -443CC carriers than TT carriers (P <0.001). Both the CC carriers and OPN expression were closely associated with the cervical lymph node metastasis and angiolymphatic invasion of PTC. Conclusion: This study provides evidence to support the connection between the OPN genetic polymorphism and tissue expression with risk as well as the invasiveness of PTC.

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Section: Discussionmentioning

confidence: 99%

“…The expression of OPN was significantly influenced by its genetic polymorphisms of the promoter [25]. Several polymorphisms in the human OPN encoding gene have been identified in different populations, of which the -156 GG>G genotype and -443 T>C polymorphisms were the most studied.…”

Section: Introductionmentioning

confidence: 99%

OPN -443C>T Genetic Polymorphism and Tumor OPN Expression are Associated with the Risk and Clinical Features of Papillary Thyroid Cancer in a Chinese Cohort

Wang

Cai

et al. 2013

Cell Physiol Biochem

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“…The -443 T>C polymorphism is at the binding site of MYT1 zinc finger factor and has been formerly correlated to the development of neurogenesis and the status of hepatitis activity [29]. The -156 G>GG polymorphism may interfere with the binding affinity of transcription factor, RUNX2, and has been associated with the increased risk of systemic lupus erythematous [30] and oral squamous cell carcinoma [12,31,32]. As for the -66 G>T polymorphism, its implications in disease development have yet been established.…”

Section: Discussionmentioning

confidence: 99%

“…Our study indicates that the higher frequency of the -66 GG genotypic carriers among the CSM patients, compared with the paired control. Although the underlying mechanisms are unclear, studies have shown that the expression of OPN is significantly affected by transcription factors and the genetic polymorphisms in the promoter [12]. Thereby, we compared the levels of OPN expression in the intervertebral disc and ligament samples from CSM patients among the -66TT, -66GG and -66GT carriers.…”

Section: Discussionmentioning

confidence: 99%

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OPN Polymorphism is Associated with the Susceptibility to Cervical Spondylotic Myelopathy and its Outcome After Anterior Cervical Corpectomy and Fusion

Guo

et al. 2014

Cell Physiol Biochem

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Background: Osteopontin (OPN) is reportedly involved in bone desorption, formation and ectopic calcification. We sought to investigate the role of OPN gene polymorphism in the susceptibility to Cervical spondylotic myelopathy (CSM) and in predicting the outcome anterior cervical corpectomy and fusion (ACF). Methods: A total of 187 patients diagnosed with CSM and 233 sex and age matched healthy controls were enrolled in this study. All CSM patients received ACF and were followed up for 24 months. The polymorphisms of OPN gene at 3 loci, namely, -156 G>GG, -443 C>T and -66T>G were determined. Results: The -66T>G genotype was significantly different between CSM patients and controls. Compared to the -66TT carriers, the -66GG genotype carriers had a higher risk for developing CSM (adjusted Odd Ratio=2.58, adjusted P=0.001). In contrast, the genotype distributions of the -156G/GG and -443C/T loci were not significantly different between the CSM and control groups. OPN gene polymorphism did not determine the pre-operative severity of CSM patients, but the -66T>G genotype was significantly associated with the clinical outcome of CSM after ACF treatment. The -66T>G did not affect the serum OPN level, but affect the local expressions of OPN and a serious of key inflammatory factors in the intervertebral disc samples. Conclusion: Our study shows the OPN -66T>G genetic polymorphism contributes to patients' susceptibility to CSM and could be indicative of the outcome of ACF surgery.

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Osteopontin promoter polymorphisms at locus -443 significantly affect the metastasis and prognosis of human hepatocellular carcinoma

et al. 2013

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Osteopontin (OPN) plays a crucial role in hepatocellular carcinoma (HCC) metastasis. However, little is known about the impact of OPN polymorphisms on cancer progression. In this study, we first identified the single nucleotide polymorphisms (SNPs) in the OPN promoter region by direct sequencing in 30 HCCs, and then evaluated the prognostic values of the selected ones in two large cohorts of 826 HCC patients. The identified SNPs were functionally analyzed using in vitro and in vivo assays and their correlations with OPN levels were also evaluated. Only SNP at locus -443 and their related haplotypes (Ht2: -1748A/-616G/-443T/-155* [*indicates base deletion]; Ht3: -1748A/-616G/-443C/-155*) were significantly associated with overall survival (OS) and time to recurrence (TTR). The patients with the -443TT/TC genotype or Ht2 had a shorter OS and TTR compared with those with -443CC genotype or Ht3. This was further confirmed in the validation cohort. Moreover, this correlation remained significant in patients with small HCCs ( 5 cm). Multivariate analyses indicated that the prognostic performance of the -443 genotypes (OS, P 5 0.031; TTR, P 5 0.005) and their related haplotypes (OS, P 5 0.002; TTR, P 5 0.001) was independent of other clinicopathological factors. The Ht2 and -443TT genotype could significantly increase the promoter transcriptional activity and expression level of OPN compared with the Ht3 or -443CC genotype, and lead to an obvious increase in both in vitro invasion and in vivo tumor growth and lung metastasis of HCC cells (P < 0.05). Conclusion: The genetic variation at locus -443 of the OPN promoter plays important roles in the regulation of OPN expression and cancer progression of HCCs, which is a novel determinant and target for HCC metastasis and prognosis. (HEPATOLOGY 2013;57:1024-1034 D uring the past decades, although much progress has been achieved in the clinical management of hepatocellular carcinoma (HCC), its prognosis remains dismal. 1,2 Thus, to develop effective individualized treatments based on molecular classification is pivotal to improve the prognosis of HCC patients.Osteopontin (OPN) is a secreted noncollagenous, sialic-acid-rich, chemokine-like extracellular matrix (ECM) protein. OPN binds to avb integrins and receptors of the CD44 family to promote cell adhesion, chemotaxis, ECM degradation, angiogenesis, prevention of apoptosis, and indolent tumor growth. 3 Moreover, it plays a crucial role in determining the oncogenic potential of various cancers, contributing to tumor invasion and metastasis. [4][5][6] In HCC increased OPN levels are associated with metastasis, poor prognosis, and early tumor recurrence. [7][8][9]

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The implication of osteopontin (OPN) expression and genetic polymorphisms of OPN promoter in oral carcinogenesis

Cited by 36 publications

References 24 publications

OPN -443C>T Genetic Polymorphism and Tumor OPN Expression are Associated with the Risk and Clinical Features of Papillary Thyroid Cancer in a Chinese Cohort

OPN -443C>T Genetic Polymorphism and Tumor OPN Expression are Associated with the Risk and Clinical Features of Papillary Thyroid Cancer in a Chinese Cohort

OPN Polymorphism is Associated with the Susceptibility to Cervical Spondylotic Myelopathy and its Outcome After Anterior Cervical Corpectomy and Fusion

Osteopontin promoter polymorphisms at locus -443 significantly affect the metastasis and prognosis of human hepatocellular carcinoma

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