Unravelling the role of immune cells and FN1 in the recurrence and therapeutic process of skull base chordoma
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ABSTRACT:
SUBMITTER: Huo X
PROVIDER: S-EPMC10545891 | biostudies-literature | 2023 Oct
REPOSITORIES: biostudies-literature
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Project description:The prognostic factors of skull base chordoma associated with outcomes of patients after surgical resection remain poorly defined. This project aimed to identify a novel prognostic factor for patients with skull base chordoma. Using a proteomics approach, we screened tumor biomarkersthat upregulated in the rapid-recurrence group of chordoma, narrowed down by bioinformatics analysis, and finally potential biomarker was chosen for validation by immunohistochemistry using tissue microarray.
2021-11-03 | PXD025894 | Pride
Project description:Chordoma is a rare bone tumor with an unknown etiology and high recurrence rate. Here we conduct whole genome sequencing of 80 skull-base chordomas and identify PBRM1, a SWI/SNF (SWItch/Sucrose Non-Fermentable) complex subunit gene, as a significantly mutated driver gene. Genomic alterations in PBRM1 (12.5%) and homozygous deletions of the CDKN2A/2B locus are the most prevalent events. The combination of PBRM1 alterations and the chromosome 22q deletion, which involves another SWI/SNF gene (SMARCB1), shows strong associations with poor chordoma-specific survival (Hazard ratio [HR] = 10.55, 95% confidence interval [CI] = 2.81-39.64, p = 0.001) and recurrence-free survival (HR = 4.30, 95% CI = 2.34-7.91, p = 2.77 × 10-6). Despite the low mutation rate, extensive somatic copy number alterations frequently occur, most of which are clonal and showed highly concordant profiles between paired primary and recurrence/metastasis samples, indicating their importance in chordoma initiation. In this work, our findings provide important biological and clinical insights into skull-base chordoma.
| S-EPMC7859411 | biostudies-literature
Project description:Objective/hypothesisTo investigate the clinical features, management strategies and outcomes for patients with metastatic primary skull base chordomas.Study designSystematic review.MethodsA systematic search through Pubmed/Medline, Web of Science, and EBSCOhost (CINAHL) was conducted without restriction on dates. After study screening and full-text assessment, two authors independently extracted all data using a pre-established abstraction form.ResultsForty cases were included from 38 studies. The average age (standard deviation [SD]) of the sample at presentation was 28.5 (23.3) and was equally distributed across genders. The average time (SD) between initial diagnosis to local recurrence was 40.1 (60.3) months. The average time (SD) from primary tumor detection to the diagnosis of metastatic disease was 55.2 (49.0) months. The most common subsite for metastatic spread were the lungs (32.5%). Of the 33 patients with data on outcomes, 48.5% were found to have expired by the time of publication. The median overall survival was estimated to be 84 months (95% confidence interval [CI] 62.3-105.7).ConclusionsThe most common subsites for metastatic spread of skull base chordoma were the lungs and bone. Overall survival for patients in the current cohort was a median of 84 months, with no significant differences noted when stratifying by the extent of surgery or the site of metastases.Level of evidence3a.
| S-EPMC9575061 | biostudies-literature
Project description:BackgroundThe prognostic factors of skull base chordoma associated with outcomes of patients after surgery remain inadequately identified. This study was designed to identify a novel prognostic factor for patients with skull base chordoma.MethodUsing a proteomic technique, the tumor biomarkers that were upregulated in the rapid-recurrence group of chordoma were screened and then narrowed down by bioinformatic analysis. Finally one potential biomarker was chosen for validation by immunohistochemistry using tissue microarray (TMA). A total of 187 patients included in TMA were randomly divided into two cohorts, the training cohort included 93 patients and the validation cohort included 94 patients. Kaplan-Meier survival analysis was used to assess the patients' survival. Univariable and multivariable Cox regression analysis were used to identify prognostic factors predicting recurrence-free survival (RFS). CCK-8 assay, clonal formation assay and transwell assay were used to test the effect of asparagine synthetase (ASNS) on the proliferation, migration and invasion in chordoma cell lines.ResultsAmong 146 upregulated proteins, ASNS was chosen as a potential prognostic biomarker after bioinformatics analysis. The H-scores of ASNS ranged from 106.27 to 239.58 in TMA. High expression of ASNS was correlated with shorter RFS in both the training cohort (p = 0.0093) and validation cohort (p < 0.001). Knockdown of ASNS by small interfering RNA (siRNA) inhibited the growth, colony formation, migration and invasion of chordoma cells in vitro.ConclusionThis study indicates that high expression of ASNS is correlated with poor prognosis of patients with skull base chordoma. ASNS may be a useful prognostic factor for patients with skull base chordoma.
| S-EPMC8440958 | biostudies-literature
Project description:Skull base chordoma is a primary rare malignant bone-origin tumor showing relatively slow growth pattern and locally destructive lesions, which can only be characterized by histologic components. There is no available prognostic or therapeutic biomarker to predict clinical outcome or treatment response and the molecular mechanisms underlying chordoma development still remain unexplored. Therefore, we sought out to identify novel somatic variations that are associated with chordoma progression and potentially employed as therapeutic targets. Thirteen skull base chordomas were subjected for whole-exome and/or whole-transcriptome sequencing. In process, we have identified chromosomal aberration in 1p, 7, 10, 13 and 17q, high frequency of functional germline SNP of the T gene, rs2305089 (P = 0.0038) and several recurrent alterations including MUC4, NBPF1, NPIPB15 mutations and novel gene fusion of SAMD5-SASH1 for the first time in skull base chordoma.
| S-EPMC5352057 | biostudies-literature
Project description:ObjectiveChordoma is a slow-growing and locally aggressive cancer, which arises from the remnants of the primitive notochord. The first line treatment for the skull base chordoma is neurosurgery. Gamma Knife radiosurgery (GKS) is often be chosen especially in the setting of residual or recurrent chordomas. The purpose of this study is to evaluate the prognosis of patients with skull base chordoma who underwent GKS.MethodsThe present study was a retrospective analysis of 53 patients with skull base chordomas who underwent GKS. Univariate Cox and Kaplan-Meier survival analysis were performed to analyze the relationship between the tumor control time and the clinical characteristics.ResultsThe 1-, 2-, 3-, and 5-year progression free survival (PFS) rates were 87, 71, 51, and 18%, respectively. After performing the univariate analysis, the clinical characteristics were not found to be significantly associated with the time of PFS; however, surgical history, peripheral dose, and tumor volume did have tendencies to predict the prognosis.ConclusionGKS provided a safe and relatively effective treatment for residual or recurrent chordomas after surgical resection. A higher tumor control rate depends on two approaches, an appropriate dose of radiation for the tumor and the accurate identification of the tumor margins.
| S-EPMC9947462 | biostudies-literature
Project description:Background and purposeChordoma and chondrosarcoma of the skull base are rare tumors with overlapping presentations and anatomic imaging features but different prognoses. We hypothesized that these tumors might be distinguished by using diffusion-weighted MR imaging.Materials and methodsWe retrospectively reviewed 19 patients with pathologically confirmed chordoma or chondrosarcoma who underwent both conventional and diffusion-weighted MR imaging. Differences in distributions of ADC were assessed by the Kruskal-Wallis test. Associations between histopathologic diagnosis and conventional MR imaging features (T2 signal intensity, contrast enhancement, and tumor location) were assessed with the Fisher exact test.ResultsChondrosarcoma was associated with the highest mean ADC value (2051 ± 261 × 10(-6) mm(2)/s) and was significantly different from classic chordoma (1474 ± 117 × 10(-6) mm(2)/s) and poorly differentiated chordoma (875 ± 100 × 10(-6) mm(2)/s) (P < .001). Poorly differentiated chordoma was characterized by low T2 signal intensity (P = .001), but other conventional MR imaging features of enhancement and/or lesion location did not reliably distinguish these tumor types.ConclusionsDiffusion-weighted MR imaging may be useful in assessing clival tumors, particularly in differentiating chordoma from chondrosarcoma. A prospective study of a larger cohort will be required to determine the value of ADC in predicting histopathologic diagnosis.
| S-EPMC7964651 | biostudies-literature
Project description:Skull base chordoma is a rare tumor with unknown risk factors. Werner syndrome, which is caused by a mutation in the WRN gene, is a disease of progeria, resembling the pathological process of aging. The present study aimed to provide data on the possible association between skull base chordoma and the single-nucleotide polymorphism (SNP) rs1346044 of the WRN gene. Between July, 2010 and September, 2012, a total of 65 patients with pathologically confirmed skull base chordoma and 65 control subjects were enrolled in this case-control study. The clinical data of the skull base chordoma patients were documented and the rs1346044 site in all the enrolled subjects was analyzed by sequencing and statistically compared using SPSS software. The A allele was the dominant allele of the rs1346044. The comparisons of genotype distributions and allele frequencies did not reveal any significant difference between the groups [P=0.383, 95% confidence interval (CI): 0.346-1.505]. The clinicopathological factors were assessed and no statistically significant difference was observed. In conclusion, the present study suggested that there is no association between rs1346044 SNP and skull base chordomas, at least in the population analyzed.
| S-EPMC4051466 | biostudies-literature
Project description:Inflammation associated markers and nutritional indexes are associated with survival, and act as novel prognostic grading systems in patients with cancer, though the role of these markers in chordoma remains unclear. The current study aimed to characterize systemic immune-inflammation index (SII) and prognostic nutritional index (PNI), and their relationship with clinicopathological data and survival in skull base chordoma. Our retrospective study enrolled 183 patients with primary skull base chordoma who received surgical treatment. Clinicopathological data and preoperative blood tests including neutrophil, lymphocyte, platelet counts and albumin level were collected from medical records. Neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), SII, PNI were calculated and the optimal cut-off values of these markers were used for further survival analysis via Kaplan-Meier survival analysis and Cox proportional hazards regression analysis. The value of NLR, PLR, SII, and PNI in skull base chordoma ranged from 0.44-6.48, 45.36-273.94, 113.37-1761.45, and 43.40-70.65, respectively. PNI was significantly correlated with patients' sex (p = 0.005) and age (p = 0.037). SII was positively correlated with NLR and PLR, but negatively correlated with PNI. The median overall survival (OS) time was 74.0 months and Kaplan-Meier survival analysis indicated that all four indexes were associated with OS. Multivariable Cox proportional hazards regression analysis identified that high SII was an independent prognostic factor for poor OS. More importantly, patients with high SII and PNI had the worst outcomes and combined use of SII and PNI increased the predictive ability for patients' survival in skull base chordoma. Our results suggest SII and PNI may be effective prognostic indicators of OS for patients with primary skull base chordoma after surgical resection.
| S-EPMC7947628 | biostudies-literature
Project description:Skull-base chordoma (SBC) is a rare, aggressive bone cancer with a high recurrent rate. Genomic studies of SBC have improved our understanding of the disease’s biology. However, the molecular biological characteristics and the effective therapy of SBC remain unknown. Here, we carried out an integrative genomics, transcriptomics, proteomics, and phosphoproteomics analysis of 187 skull-base chordoma tumors. We identified chromosome instability (CIN) as a prognostic predictor and a potential therapeutic target in SBCs. Multi-omic data revealed downstream effects of CIN, in which, RPRD1B served as a putative therapeutic target for radiotherapy resistant SBC patients. Chromosome 1q gain was significantly enriched in CIN+ SBCs, and associated with upregulated mitochondrial functions, which led to inferior clinical outcomes. Immune subtyping identified an immune cold SBC subtype with CIN+ feature, and elucidated an association between losses of chromosome 9p/10q and immune evasion. In addition, proteomics-based classification of SBCs revealed that P-II and P-III subtype tumors had both CIN+ and immune cold features; however, P-II tumors with apoptosis suppression features were more invasive. These identified molecular features of CIN were further confirmed in 17 pairwise SBC patients. Our observations and the multi-omic data resources might guide research into the biology and treatment of SBC.
2024-07-01 | PXD053550 |