OPN Gene Polymorphism and the Serum OPN Levels Confer the Susceptibility and Prognosis of Ischemic Stroke in Chinese Patients

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.

Section: Discussionmentioning

confidence: 48%

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

Tian¹,

Yao²,

Song³

et al. 2014

“…A series of cyclins and cyclin-dependent kinases (cdks) are known to play a central role in the regulation of cell cycle progression [34,37], and their activity is modulated by cdk inhibitors. Mice lacking p27 kip1 , a cdk inhibitor, have an increased propensity to develop multiorgan neoplasia, such as pituitary tumor [38,39,40]. Interestingly, mutations of the p27 kip1 gene do not seem to play a role in human pituitary carcinogenesis [34,40], however Gal-3 expression was markedly elevated in p27-null mice that develop pituitary hyperplasia and intermediated lobe of ACTH cell pituitary tumors [17,41,42].…”

Section: Discussionmentioning

confidence: 99%

GAL3 Protein Expression is Related to Clinical Features of Prolactin-Secreting Pituitary Microadenoma and Predicts its Recurrence after Surgical Treatment

Dai

Li²,

Lu³

et al. 2014

Background: Previous in vitro study showed that Galectin-3 (Gal-3) protein plays an important role in pituitary tumorigenesis, however, the association of Gal-3 expression with the clinical feature and prognosis of pituitary tumor in a clinical setting remains unknown. Methods: We enrolled 220 patients with prolactin-secreting pituitary adenomas (PA) who previously had transsphenoidal pituitary surgery. The Gal-3 expression was detected in the patients' PA samples using immunohistochemistry and those patients were followed up. A prolactin-secreting PA cell line, the MMQ cell line, was used to study the in vitro effect of Gal-3 on proliferation, migration and invasion of PA cells using small interfering RNA (siRNA) transfecton technique. The in vivo tumorgenesis in nude mice was also studied. Results: We found that Gal-3 expression was not related to age and sex, but positively associated with tumor invasion (P<0.001), tumor sizes (P<0.001) and pre-operative prolactin levels (P<0.001). The multivariate Cox analysis showed that the Gal-3 expression was closely associated with the recurrence of PA after the surgical treatment (HR =3.15, P=0.002). The in vitro studies showed that Gal-3 knock-down by the siRNA technique significantly inhibited the proliferation, migration and invasion ability of the MMQ cells, whereas Gal-3 siRNA transfection induced apoptosis of the MMQ cells. The in vivo tumorgenesis assay showed that Gal-3 siRNA transfection significantly inhibited the tumor volume in vivo compared to transfection of the control siRNA (P<0.001). Conclusion: Gal-3 regulates proliferation, apoptosis, migration and invasion of the MMQ cells. Gal-3 may be used as a tissue marker to evaluate the clinical feature and prognosis of PA patients.

“…The OPN encoding gene is mapped on human chromosome 4q21-q25 and polymorphisms in the OPN gene promoter can affect its transcriptional activity [31,32]. More than fifty single nucleotide polymorphisms have been identified in the human OPN encoding gene in different populations, of which three single nucleotide polymorphisms on the promoter region of OPN gene, namely, -66T>G (rs28357094), -156G>GG (rs17524488), and -443C>T (rs11730582), have been extensively studied [31].…”

Section: Discussionmentioning

confidence: 99%

Polymorphism -433 C>T of the Osteopontin Gene is Associated with the Susceptibility to Develop Gliomas and their Prognosis in a Chinese Cohort

Shen

Chen²,

Hou

et al. 2014

Self Cite

Aim: To investigate role of the Osteopontin (OPN) genetic polymorphisms in the susceptibility to gliomas and their prognosis. Methods: A total of 248 Chinese glioma patients and 281 age and sex matched healthy controls were recruited. The genetic polymorphisms at three loci, namely, -156 GG>G, -443 C>T and -66T>G, were determined. The log-rank test and Kaplan- Meier analysis were introduced to assess the effect of OPN gene polymorphisms on patient survival. Results: We found that the genotype frequencies of OPN -443 C>T polymorphism were significantly different between glioma patients and controls. Multivariable analyses showed a higher risk for gliomas in -443 CC genotype carriers compared to -443TT carriers (P<0.001). In addition, we also found the OPN -443 C>T polymorphism was closely related to the gliomas' tumor grade. The -443 C>T polymorphism also affected the tumor OPN expression level, but not the serum OPN level. More importantly, the -443 C>T polymorphism was significantly associated with the prognosis of these patients regardless of their treatment status. The patients with -443CC genotype had a poorer prognosis than those with -443TT and -443CT genotypes. In contrast, the -156 G>GG and -66T>G polymorphisms were not associated with risk, clinical characteristics, or prognosis of gliomas. Conclusion: This study suggests that the -443C>T gene polymorphisms may be used as a molecular marker for glioma occurrence and clinical outcome in glioma patients. © 2014 S. Karger AG, Basel