BackgroundAberrant expression of C-X-C motif chemokine 5 (CXCL5) contributes to the progression of various cancers. This study analyzed the clinical significance of serum CXCL5 (sCXCL5) levels of nasopharyngeal carcinoma (NPC) patients, with the goal of building a novel prognostic score model.Experimental DesignSerum samples were collected prior to treatment from 290 NPC patients for the detection of sCXCL5 with ELISA. Half of the patients (n = 145) were randomly assigned to the training set to generate the sCXCL5 cutoff point using receiver operator characteristic (ROC) analysis, while the other half (n = 145) were assigned to the testing set for validation. Associations between sCXCL5 levels and clinical characteristics were analyzed. A prognostic score model was built using independent predictors derived from multivariate analysis. A concordance index (C-Index) was used to evaluate prognostic ability.ResultsThe sCXCL5 cutoff point was 0.805 ng/ml. Sex, age, histology, T classification, clinical classification and local recurrence were not associated with sCXCL5 levels. However, sCXCL5 levels were positively associated with N classification, distant metastasis and disease progression (P<0.05). A high sCXCL5 level predicted poor 6-year overall survival (OS), poor 6-year distant metastasis-free survival (DMFS), and poor 6-year progression-free survival (PFS). A prognostic score model was subsequently constructed based on sCXCL5 levels and clinical classification (C-C model), which are independent predictors of OS, DMFS, and PFS, as confirmed by the multivariate analysis. Furthermore, this novel model successfully divided the patients into four risk subgroups in the training set, the testing set and the entire set of patients. The C-Indices were 0.751 and 0.762 for the training set and the testing set, respectively.ConclusionssCXCL5 level was determined to be an independent prognostic factor for NPC patients. The novel statistical C-C model, which includes sCXCL5 levels and clinical classification, could be helpful in predicting the prognosis of NPC patients.
Sacrococcygeal teratomas (SCT) in adults are extremely rare, and most SCTs are located either mainly outside the pelvis, with a small number of intrapelvic components, or mostly in the pelvis (types III and IV). The etiology of teratomas remains unknown. Most teratomas are benign, and approximately 1 to 2% of teratomas undergo malignant transformation, including squamous cell carcinoma, adenocarcinoma, sarcoma, and other malignancies. Most SCTs grow insidiously, and their symptoms are not easily detected in the early stages. Some cases may only be discovered through physical examination or compression symptoms when the tumor reaches a detectable size. Computed tomography and magnetic resonance imaging have high detection rates for presacral space-occupying lesions and can provide imaging details with guiding significance for the selection of surgical methods. Surgical resection is the preferred treatment option for SCT and can determine the pathological type. Common sacrococcygeal malignancies are mainly immature teratomas and mature teratomas. When the presence of malignant components is confirmed, the treatment model should be adjusted according to pathological type.
Risk classification on the basis of specific genomic features can lead to more precise tailoring of treatment for cancer patients. Kinases are potential therapeutic targets and survival factors, but the predictive prognostic potentials of multi-kinase genes have seldom been investigated. In this study, with publicly available microarray data of non-small cell lung cancers (NSCLC), we identified two kinase genes cyclin-dependent kinase 2 (CDK2) and p21 protein (Cdc42/Rac)-activated kinase 4 (PAK4) significantly associated with poor outcome. Then we present a combined gene signature model using CDK2 and PAK4 that can stratify disease poor outcome independently of standard clinical prognostic factors. Next, the predictive robustness of this 2-gene classifier was in silico confirmed in an independent microarray dataset, and experimentally validated in a lung cancer cohort by immunohistochemistry. Therefore, in this study, we demonstrated that the CDK2-PAK4 kinase signature may be a useful prognostic indicator and potential target for NSCLC. We also propose that poor outcome subgroup stratified by this classifier may benefit from the recently developed CDK2 and PAK4 inhibitors.
Serglycin is a proteoglycan consisting of a core protein to which negatively charged glycoaminoglycan (GAG) chains of either chondroitin sulfate or heparin are attached. Serglycin was first shown to be essential for the maturation of mast cell secretory granules, but it has recently been shown to be present within multiple other cell types. In this study we describe for the first time the role of serglycin as a potential metastasis regulator in nasopharyngeal carcinoma (NPC), a tumor that has the highest incidence of metastasis among head and neck cancers. The recognition that serglycin plays an important role in NPC comes from our earlier genomic expression profiles comparing clones derived from the NPC cell line CNE-2, where serglycin (SRGN) was identified as one of the most up-regulated genes in the high-metastasis Clone 18. The genomic expression profiling was performed on samples collected in cultured cells and in xenograft tumors generated from Clone-18, as well as low-metastasis clones (Clone-22, Clone-26) and their parental line, CNE-2. A popliteal lymph node model was used to evaluate the metastasis ability of different cellular populations. A tissue microarray was constructed from 330 NPC tissues and a total of 263 cases were informative for assessing the patients’ survival duration. A deglycosylation assay, lentiviral transduction, quantitative PCR, proliferation assay, Transwell assay, and wound-healing assay were used for the functional studies. The serglycin protein was shown to be secreted by the high-metastasis clone, but not by any of the low-metastasis clones. Suppression of serglycin by shRNA diminished serglycin secretion and subsequently inhibited migration and invasion by the high-metastasis clone, and also significantly reduced its metastasis rate in vivo. Overexpression of serglycin in low-metastasis cells resulted in a significantly increased metastasis rate in vivo. Moreover, secreted serglycin promoted cellular motility in the wild-type low-metastasis cells. Interestingly, suppression of serglycin reduced the protein level of vimentin but did not influence the level of E-cadherin in the high-metastasis clone. Proliferation was not influenced by serglycin in either the high- or low-metastasis clones. Importantly, in direct tumor samples, serglycin expression was significantly elevated in liver metastases from NPC relative to its expression in primary tumors. In conclusion, serglycin appears to play a potentially pivotal role in regulating NPC metastasis by way of enhancing cellular migration, cellular invasiveness, vimentin expression level, and the in vivo spread of cancer cells. Moreover, a high level of serglycin expression can potentially be used to predict shorter disease-free survival and shorter metastasis-free survival of NPC patients. Targeting serglycin could be a novel option for the prevention of NPC metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1476. doi:10.1158/1538-7445.AM2011-1476
It has been reported that 18F-FDG uptake is higher in hypoxic cancer cells than in well-oxygenated cells. We demonstrated that 18F-FDG uptake in lung cancer would be affected by high concentration oxygen breathing. Methods. Overnight fasted non-small-cell lung cancer A549 subcutaneous (s.c.) xenografts bearing mice (n = 10) underwent 18F-FDG micro-PET scans, animals breathed room air on day 1, and same animals breathed carbogen (95% O2 + 5% CO2) on the subsequent day. In separated studies, autoradiography and immunohistochemical staining visualization of frozen section of A549 s.c. tumors were applied, and to compare between carbogen-breathing mice and those with air breathing, a combination of 18F-FDG and hypoxia marker pimonidazole was injected 1 h before animal sacrifice, and 18F-FDG accumulation was compared with pimonidazole binding and glucose transporter 1 (GLUT-1) expression. Results. PET studies revealed that tumor 18F-FDG uptake was significantly decreased in carbogen-breathing mice than those with air breathing (P < 0.05). Ex vivo studies confirmed that carbogen breathing significantly decreased hypoxic fraction detected by pimonidazole staining, referring to GLUT-1 expression, and significantly decreased 18F-FDG accumulation in tumors. Conclusions. High concentration of O2 breathing during 18F-FDG uptake phase significantly decreases 18F-FDG uptake in non-small-cell lung cancer A549 xenografts growing in mice.
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