Clinicopathological significance of p16, cyclin D1, Rb and MIB‐1 levels in skull base chordoma and chondrosarcoma

Liu, Junqi; Zhang, Qiuhang; Wang, Zhenlin

doi:10.1016/j.wjorl.2015.09.005

Cited by 8 publications

(6 citation statements)

References 27 publications

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“…Previous studies have shown that factors affecting prognosis include patient's age, tumor size, tumor site, and vascular involvement (5)(6)(7). Meanwhile, some molecular markers such as high expression of Ki-67 and MIB-1 are associated with poor prognosis and high recurrence rate (8)(9)(10). However, the effect of the extent of surgical resection on skull base chordoma prognosis is not clear and needs to be further studied.…”

Section: Introductionmentioning

confidence: 99%

Multivariate Analysis and Validation of the Prognostic Factors for Skull Base Chordoma

et al. 2021

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Background: Skull base chordoma is a rare tumor with low-grade malignancy and a high recurrence rate, the factors affecting the prognosis of patients need to be further studied. For that, we investigated prognostic factors of skull base chordoma through the database of the Surveillance, Epidemiology, and End Results (SEER) program, and validated in an independent data set from the Xiangya Hospital.Methods: Six hundred and forty-three patients diagnosed with skull base chordoma were obtained from the SEER database (606 patients) and the Xiangya Hospital (37 patients). Categorical variables were selected by Chi-square test with a statistical difference. Survival curves were constructed by Kaplan–Meier analysis and compared by log-rank test. Univariate and multivariate Cox regression analyses were used to explore the prognostic factors. Propensity score matching (PSM) analysis was undertaken to reduce the substantial bias between gross total resection (GTR) and subtotal resection (STR) groups. Furthermore, clinical data of 37 patients from the Xiangya Hospital were used as validation cohorts to check the survival impacts of the extent of resection and adjuvant radiotherapy on prognosis.Results: We found that age at diagnosis, primary site, disease stage, surgical treatment, and tumor size was significantly associated with the prognosis of skull base chordoma. PSM analysis revealed that there was no significant difference in the OS between GTR and STR (p = 0.157). Independent data set from the Xiangya Hospital proved no statistical difference in OS between GTR and STR groups (p = 0.16), but the GTR group was superior to the STR group for progression-free survival (PFS) (p = 0.048). Postoperative radiotherapy does not improve OS (p = 0.28), but it can prolong PFS (p = 0.0037). Nomograms predicting 5- and 10-year OS and DSS were constructed based on statistically significant factors identified by multivariate Cox analysis. Age, primary site, tumor size, surgical treatment, and disease stage were included as prognostic predictors in the nomograms with good performance.Conclusions: We identified age, tumor size, surgery, primary site, and tumor stage as main factors affecting the prognosis of the skull base chordoma. Resection of the tumor as much as possible while ensuring safety, combined with postoperative radiotherapy may be the optimum treatment for skull base chordoma.

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Section: Introductionmentioning

confidence: 99%

Multivariate Analysis and Validation of the Prognostic Factors for Skull Base Chordoma

et al. 2021

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“…The p16 gene can inhibit the progression of a variety of tumors and encode the nucleotide protein (p16 protein) to significantly inhibit the cyclin-dependent kinase 4 (CDK4), thus playing an important role in the progression of various tumors (6). Cyclin D1, as a key cell cycle regulatory protein, can bind to CDK4/6 to form the binary complex and keep cells in S phase, thus promoting cell proliferation (7). Dreyer et al (8) showed that both p16 and cyclin D1 can competitively bind to CDK4, thereby regulating the occurrence and development of tumors.…”

Section: Introductionmentioning

confidence: 99%

Correlation of p16 and cyclin D1 expression with the incidence and prognosis of cardiac carcinoma

Wang

Wang²,

Zhao

2019

Oncol Lett

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Correlation of p16 and cyclin D1 expression with the incidence and prognosis of cardiac carcinoma was investigated. Thirty-six patients with cardiac carcinoma treated in The Second Affiliated Hospital of Zhengzhou University were selected. After the radical operation of cardiac carcinoma, carcinoma tissues were taken, and the corresponding para-carcinoma tissues were used as controls. p16 and cyclin D1 messenger ribonucleic acid (mRNA) and protein expression in cardiac carcinoma tissues and para-carcinoma tissues were detected via quantitative polymerase chain reaction (qPCR) and western blot analysis. The survival time and pathological conditions of patients with cardiac carcinoma were recorded in detail, and correlation of p16 and cyclin D1 with incidence and prognosis of cardiac carcinoma was studied. In cardiac carcinoma tissues, the p16 mRNA and protein expression levels were significantly lower than those in para-carcinoma tissues (P<0.01), but the cyclin D1 mRNA and protein expression levels were significantly higher than those in para-carcinoma tissues (P<0.01). The expression of p16 and cyclin D1 protein had correlation with the tumor size, lymph node metastasis and tumor-node-metastasis stage of cardiac carcinoma (P<0.01). There was a negative correlation between expression of p16 and cyclin D1 in cardiac carcinoma (P<0.01). According to Kaplan-Meier survival analysis, the survival rate of patients with high expression of p16 was obviously higher than that of patients with low expression of p16 (P<0.01), while the survival rate of patients with high expression of cyclin D1 was obviously lower than that of patients with low expression of cyclin D1 (P<0.01). Both p16 and cyclin D1 are closely related to the incidence and prognosis of cardiac carcinoma, which may become indexes for the incidence and prognosis of cardiac carcinoma.

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“…In addition, YBX1 regulates tumor cell proliferation, apoptosis, invasion, migration and chemoresistance through the related pathways . Multiple key molecules that interact with YBX1 have been shown to be overexpressed in chordoma and contribute to chordoma development, such as hypoxia inducible factor 1 alpha subunit (HIF‐1α), a mechanistic target of rapamycin kinase (mTOR) and RB transcriptional corepressor 1 (RB) …”

Section: Introductionmentioning

confidence: 99%

“…10 Multiple key molecules that interact with YBX1 have been shown to be overexpressed in chordoma and contribute to chordoma development, such as hypoxia inducible factor 1 alpha subunit (HIF-1α), a mechanistic target of rapamycin kinase (mTOR) and RB transcriptional corepressor 1 (RB). 6,[11][12][13][14] Receptor tyrosine kinases (RTK) have been proved to participate in the tumorigenesis and development of chordoma. The epidermal growth factor receptor (EGFR) is the most significantly activated RTK in chordoma.…”

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confidence: 99%

Y‐box binding protein‐1 promotes tumorigenesis and progression via the epidermal growth factor receptor/AKT pathway in spinal chordoma

Chen

Lei

et al. 2018

Cancer Science

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Chordomas are rare bone tumors with a poor prognosis and no approved targeted therapy. Y‐box binding protein‐1 (YBX1) promotes tumor growth, invasion and drug resistance. However, the role of YBX1 in chordoma is unclear. In this study, we examined the expression of YBX1 using immunohistochemistry and found that YBX1 was significantly upregulated in 32 chordoma tissues compared to distant normal tissues. In addition, YBX1 upregulation was associated with surrounding tissue invasion, recurrence and poor prognosis. Biological function studies demonstrated that YBX1 promoted cell proliferation and invasion, accelerated G1/S phase transition, and inhibited apoptosis. Further investigation revealed that YBX1 enhanced epidermal growth factor receptor (EGFR) transcription by directly binding to its promoter in chordoma cells. YBX1 regulated protein expression of p‐EGFR, p‐AKT and its downstream target genes that influenced cell apoptosis, cell cycle transition and cell invasion. YBX1 activated the EGFR/AKT pathway in chordoma and YBX1‐induced elevated expression of key molecules in the EGFR/AKT pathway were downregulated by EGFR and AKT pathway inhibitors. These in vitro results were further confirmed by in vivo data. These data showed that YBX1 promoted tumorigenesis and progression in spinal chordoma via the EGFR/AKT pathway. YBX1 might serve as a prognostic and predictive biomarker, as well as a rational therapeutic target, for chordoma.

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Clinicopathological significance of p16, cyclin D1, Rb and MIB‐1 levels in skull base chordoma and chondrosarcoma

Cited by 8 publications

References 27 publications

Multivariate Analysis and Validation of the Prognostic Factors for Skull Base Chordoma

Multivariate Analysis and Validation of the Prognostic Factors for Skull Base Chordoma

Correlation of p16 and cyclin D1 expression with the incidence and prognosis of cardiac carcinoma

Y‐box binding protein‐1 promotes tumorigenesis and progression via the epidermal growth factor receptor/AKT pathway in spinal chordoma

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