Upregulation of micro-ribonucleic acid-128 cooperating with downregulation of PTEN confers metastatic potential and unfavorable prognosis in patients with primary osteosarcoma

Tian, Zheng; Guo, Bin; Yu, Mengmeng; Wang, Chong; Zhang, Haoshaqiang; Liang, Qi; Jiang, Kunli; Cao, Li

doi:10.2147/ott.s67217

Cited by 18 publications

(16 citation statements)

References 27 publications

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“…PTEN has many important functions in the body, such as the inhibition of cell growth and differentiation (14) and promotion of cell apoptosis (15), making it one of the most noticeable tumor suppressor genes after the p53 gene. NF-κB is a transcription factor with a two-way transcriptional regulation that plays an important role in many pathophysiological processes (16–18). Loftus et al (19) reported a significant increase in NF-κB p65 expression in hepatocellular carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Expression of NF-κB and PTEN in osteosarcoma and its clinical significance

Gong

Xiang

et al. 2017

Oncol Lett

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We investigated the role of nuclear factor-κB (NF-κB) and phosphatase and tensin homolog deleted in chromosome 10 (PTEN) in the pathogenesis of osteosarcoma and its relationship with prognosis. Immunohistochemical method was used to detect the expression of NF-κB and PTEN in osteosarcoma and adjacent tissues. RT-PCR was used to detect the expression of NF-κB and PTEN mRNA in osteosarcoma and adjacent tissues. Western blotting was used to detect the expression of NF-κB and PTEN in osteosarcoma and adjacent tissues and compare their differences. The expression of NF-κB and PTEN was detected in osteosarcoma and adjacent tissues. The positive rate of NF-κB was 75.3 and 32.9%, respectively; while the positive rate of PTEN was 67.1 and 90.4%, respectively. The positive expression of NF-κB and PTEN was statistically significant. There was a negative correlation between NF-κB and PTEN expression (r=−0.502, p<0.05). The positive and negative expression of NF-κB and PTEN was statistically significant for the five-year survival (p<0.05). At gene and protein level, osteosarcoma tissues had higher expression of NF-κB, and lower expression of PTEN, which was significantly different from the adjacent tissues. In osteosarcoma, NF-κB is highly expressed, but PTEN is expressed at low level, and the two are negatively correlated. This is of great significance for the early diagnosis of osteosarcoma and prognosis.

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Section: Discussionmentioning

confidence: 99%

Expression of NF-κB and PTEN in osteosarcoma and its clinical significance

Gong

Xiang

et al. 2017

Oncol Lett

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“…Numerous tumor biopsy-based markers have been found for OS and include miR-9, miR-132, miR-145, miR-183, miR-223, and miR-128 in combination with transcript levels of phosphatase and tensin homolog ( PTEN ) (34–39), the DNA mismatch repair proteins MutS protein homolog 2 (MSH2) and MSH6 (40), hypermethylated DNA of ARF tumor suppressor (p14 ARF ) and estrogen receptor α (41), the transcription factor SOX9 (42), RAC-β serine/threonine-protein kinase (AKT2) (43), periostin (44), neuropilin-1 (45), glucose transporter protein 1 (GLUT-1) (46), and polymeric immunoglobulin receptor (pIgR) (47), amongst others. However, these markers are derived from the primary OS site and therefore discount metastases, which are important determinants for PFS (9,12,13).…”

Section: Discussionmentioning

confidence: 99%

A liquid biopsy-based method for the detection and quantification of circulating tumor cells in surgical osteosarcoma patients

Zhang

Gao

Xiao

et al. 2017

International Journal of Oncology

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A method for the enumeration and quantification of osteosarcoma (OS) circulating tumor cells (CTCs) is currently not available. A correlation between the number of CTCs and progression-free survival (PFS) has been established for other cancers, but not for OS CTCs. A method was therefore developed for CTC quantification in OS and validated in a prospective cohort of surgical patients with primary and recurrent/metastatic OS (N=23). Human OS cells, acting as CTCs, were enumerated from spiked human peripheral blood (PB) following erythrocyte and leukocyte depletion. The OS cells were quantified microscopically based on aneuploidy and a CK18−/CD45− phenotype. Aneuploidy was assayed by fluorescence in situ hybridization (FISH) using fluorescence-labeled alpha-satellite probes for the centromeres of chromosome (CEP 8). CK18 and CD45 phenotyping was performed with immunocytochemistry. HOS cells in spiked PB could be effectively retrieved with the FISH-based enumeration method, which was subsequently employed in an OS patient cohort. PB of recurrent/metastatic OS patients contained more CTCs than the PB of primary OS patients. OS patients with ≥2 CTCs per 7.5 ml of PB had worse PFS than patients whose PB contained <2 CTCs. In 2 cases, CTCs were present in PB of OS patients with negative X-ray and chest CT scans. In conclusion, our method was able to quantitate CTCs in liquid biopsies of OS patients. The number of CTCs has diagnostic and prognostic value.

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“… 4 In our previous studies, we demonstrated that the deregulation of three miRNA/mRNA combinations, including miR-128/target gene PTEN, miR-223/target gene epithelial cell transforming sequence 2, and miR-183/target gene Ezrin axes, were significantly associated with the aggressive progression of human osteosarcoma. 5 – 7 More interestingly, these combinations may function as potential prognostic markers for patients with this malignancy. 5 – 7 However, the exact mechanisms of this malignancy remain unclear, thereby posing great challenges to its clinical treatment.…”

Section: Introductionmentioning

confidence: 99%

Prognostic implications of Kindlin proteins in human osteosarcoma

Ning¹,

Zhang²,

Wang³

et al. 2017

OTT

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The Kindlin protein family, comprising Kindlin-1, Kindlin-2 and Kindlin-3, play important roles in various human cancers. Here, to explore the clinical significance of Kindlins in human osteosarcomas, quantitative real-time PCR and Western blot analyses were performed to detect the expression of Kindlin-1, Kindlin-2 and Kindlin-3 mRNAs and proteins in 20 self-pairs of osteosarcoma and adjacent noncancerous tissues. Then, immunohistochemistry was performed to examine subcellular localizations and expression patterns of Kindlin proteins in 100 osteosarcoma and matched adjacent noncancerous tissues. Kindlin-1, Kindlin-2 and Kindlin-3 protein immunostainings were localized in the cytoplasm, nucleus and cytoplasm, respectively, of tumor cells in primary osteosarcoma tissues. Statistically, the expression levels of Kindlin-1 and Kindlin-2 mRNAs and proteins in osteosarcoma tissues were all significantly higher (both P<0.01), but those of Kindlin-3 mRNA and protein were both dramatically lower (both P<0.05), than in matched adjacent noncancerous tissues. In addition, the overexpressions of Kindlin-1 and Kindlin-2 proteins were both significantly associated with high tumor grade (both P=0.01), presence of metastasis (both P=0.006), recurrence (both P=0.006) and poor response to chemotherapy (both P=0.02). Moreover, Kindlin-1 and Kindlin-2 expressions were both identified as independent prognostic factors for overall (both P=0.01) and disease-free (P=0.02 and 0.01, respectively) survivals of osteosarcoma patients. However, no associations were observed between Kindlin-3 expression and various clinicopathologic features and patients’ prognosis. In conclusion, aberrant expression of Kindlin-1 and Kindlin-2 may function as reliable markers for progression and prognosis in osteosarcoma patients, especially for tumor recurrence.

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Upregulation of micro-ribonucleic acid-128 cooperating with downregulation of PTEN confers metastatic potential and unfavorable prognosis in patients with primary osteosarcoma

Cited by 18 publications

References 27 publications

Expression of NF-κB and PTEN in osteosarcoma and its clinical significance

Expression of NF-κB and PTEN in osteosarcoma and its clinical significance

A liquid biopsy-based method for the detection and quantification of circulating tumor cells in surgical osteosarcoma patients

Prognostic implications of Kindlin proteins in human osteosarcoma

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