Mitotic Index is an Independent Predictor of Recurrence-Free Survival in Meningioma.
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ABSTRACT:
SUBMITTER: Olar A
PROVIDER: S-EPMC4297750 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSystemic inflammation and nutritional status are associated with tumor development and progression. This study investigated the prognostic value of fibrinogen/albumin ratio index (FARI) in predicting recurrence-free survival (RFS) in patients with intrahepatic cholangiocarcinoma (ICC) undergoing hepatectomy.MethodsA retrospective cohort was conducted including patients who received curative hepatectomy for ICC at our hospital between May 2010 and December 2016. We collected the preoperative hematologic parameters and clinical data of all patients. Time-dependent receiver operating characteristic curve was used to identify the optimal cutoff value of FARI. The association between FARI-high and FARI-low group was investigated by using the Kaplan-Meier method. A nomogram based on the results of univariate and multivariate analysis was established.ResultsA total of 394 patients with ICC who underwent hepatectomy at our hospital were enrolled. K-M analysis revealed that increased FARI was related to reduced RFS (P < 0.001). The multivariate analysis indicated that tumor number, tumor-node-metastasis stage, lymph node metastasis, cirrhosis, serum carbohydrate antigen 19-9, and FARI were independent predictors of RFS, and the ROC curve analysis showed that the optimal cutoff value for FARI was 0.084 based on the Youden index. The nomogram for FARI showed satisfactory accuracy in predicting RFS for ICC patients undergoing hepatectomy (C index = 0.663; AIC = 3081.07).ConclusionPreoperative FARI is an independent predictor of RFS in patients undergoing hepatectomy for ICC, and the nomogram can be useful for clinical decision-making in the postoperative management of these patients.
| S-EPMC8293519 | biostudies-literature
Project description:Meningioma is the most common primary brain tumor and has a variable risk of local recurrence. While World Health Organization (WHO) grade generally correlates with recurrence, there is substantial within-grade variation of recurrence risk. Current risk stratification does not accurately predict which patients are likely to benefit from adjuvant radiation therapy (RT). We hypothesized that tumors at risk for recurrence have unique gene expression profiles (GEP) that could better select patients for adjuvant RT.We developed a recurrence predictor by machine learning modeling using a training/validation approach.Three publicly available AffymetrixU133 gene expression datasets (GSE9438, GSE16581, GSE43290) combining 127 primary, non-treated meningiomas of all grades served as the training set. Unsupervised variable selection was used to identify an 18-gene GEP model (18-GEP) that separated recurrences. This model was validated on 62 primary, non-treated cases with similar grade and clinical variable distribution as the training set. When applied to the validation set, 18-GEP separated recurrences with a misclassification error rate of 0.25 (log-rank p=0.0003). 18-GEP was predictive for tumor recurrence [p=0.0008, HR=4.61, 95%CI=1.89-11.23)] and was predictive after adjustment for WHO grade, mitotic index, sex, tumor location, and Simpson grade [p=0.0311, HR=9.28, 95%CI=(1.22-70.29)]. The expression signature included genes encoding proteins involved in normal embryonic development, cell proliferation, tumor growth and invasion (FGF9, SEMA3C, EDNRA), angiogenesis (angiopoietin-2), cell cycle regulation (CDKN1A), membrane signaling (tetraspanin-7, caveolin-2), WNT-pathway inhibitors (DKK3), complement system (C1QA) and neurotransmitter regulation (SLC1A3, Secretogranin-II).18-GEP accurately stratifies patients with meningioma by recurrence risk having the potential to guide the use of adjuvant RT.
| S-EPMC5882319 | biostudies-literature
Project description:Background:Meningioma is the most common primary intracranial tumor and recurrence is one of the important challenges in patient management. Prognostic factors for tumor recurrences in these patients especially before surgical resection are not fully characterized. Several studies have indicated an association between changes in hematologic laboratory parameters with patient outcomes in solid malignancies. We aimed to assess the association between hematologic parameters and tumor recurrence in patients with meningioma. Methods:Preoperative complete blood count (CBC) data were analyzed in patients with newly diagnosed meningioma (n = 222). Clinical data, including history of corticosteroid therapy, tumor characteristics, and follow-up, were obtained. Recurrence-free survival (RFS) was evaluated using Cox proportional hazards models and log-rank tests. Results:Using preoperative CBC data from patients prior to any steroid therapy, 51 (23%) patients had neutrophilia. In univariate analysis, neutrophilia was significantly associated with meningioma recurrence (hazard ratio [HR] 2.73; P < 0.01). Neither leukocytosis nor lymphocytosis was associated with RFS. In multivariate analysis, after adjusting for tumor grade, tumor size, and extent of resection, neutrophilia remained an independent prognostic factor for RFS (HR 2.23, P = 0.01). Forty-six (21%) patients had low hemoglobin levels indicative of anemia, and the presence of anemia showed a trend toward high risk for recurrence (HR 1.83; P = 0.06). Conclusions:The presence of neutrophilia was associated with higher rate of tumor recurrence in patients with meningioma. Validation of these results and the biologic role of neutrophilic inflammatory/immune reaction in meningioma requires further investigation.
| S-EPMC5737603 | biostudies-literature
Project description:Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer.HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS).Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade.HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.
| S-EPMC3087316 | biostudies-other
Project description:Meningioma is the most common primary brain tumor and carries a substantial risk of local recurrence. Methylation profiles of meningioma and their clinical implications are not well understood. We hypothesized that aggressive meningiomas have unique DNA methylation patterns that could be used to better stratify patient management. Samples (n = 140) were profiled using the Illumina HumanMethylation450BeadChip. Unsupervised modeling on a training set (n = 89) identified 2 molecular methylation subgroups of meningioma (MM) with significantly different recurrence-free survival (RFS) times between the groups: a prognostically unfavorable subgroup (MM-UNFAV) and a prognostically favorable subgroup (MM-FAV). This finding was validated in the remaining 51 samples and led to a baseline meningioma methylation classifier (bMMC) defined by 283 CpG loci (283-bMMC). To further optimize a recurrence predictor, probes subsumed within the baseline classifier were subject to additional modeling using a similar training/validation approach, leading to a 64-CpG loci meningioma methylation predictor (64-MMP). After adjustment for relevant clinical variables [WHO grade, mitotic index, Simpson grade, sex, location, and copy number aberrations (CNAs)] multivariable analyses for RFS showed that the baseline methylation classifier was not significant (p = 0.0793). The methylation predictor, however, was significantly associated with tumor recurrence (p < 0.0001). CNAs were extracted from the 450k intensity profiles. Tumor samples in the MM-UNFAV subgroup showed an overall higher proportion of CNAs compared to the MM-FAV subgroup tumors and the CNAs were complex in nature. CNAs in the MM-UNFAV subgroup included recurrent losses of 1p, 6q, 14q and 18q, and gain of 1q, all of which were previously identified as indicators of poor outcome. In conclusion, our analyses demonstrate robust DNA methylation signatures in meningioma that correlate with CNAs and stratify patients by recurrence risk.
| S-EPMC5600514 | biostudies-literature
Project description:BackgroundFinding some convenient and economical indicators to initially screen overweight and obese patients at high risk of kidney stone recurrence can help them prevent stone recurrence with lower medical cost. The purpose of this article is to determine the clinical value of Ae index (Apo B × 1000/eGFR) as an independent predictor for kidney stone recurrence in overweight and obese populations.MethodsWe queried the electronic medical records of patients with kidney stone operated at our hospital from March 2016 to March 2022, and selected BMI ≥ 25 kg/m2 as the study population and divided the patients into stone recurrence group and non-recurrence group. Relevant parameters of routine blood and biochemical test, glycated serum protein (GSP), and history of hypertension and hyperglycemia were collected. Then the Chi-square test, independent samples t-test or Wilcoxon rank-sum test were used to calculate the differences between the two groups of data. Next, we performed univariate and multivariate logistic regression analysis to screen out the most significant variables Apo B and eGFR, and then we calculated the Ae index using the formula Apo B × 1000/eGFR, and analyzed the relationship between Ae index and kidney stone recurrence.ResultsUnivariate analysis found that Apo B (OR:8.376,95%CI:3.093-22.680), Creatinine (OR:1.012,95%CI:1.003-1.021), Cystatin C(OR:2.747,95%CI:1.369-5.508), LDL-C (OR:1.588,95%CI:1.182-2.134), TC (OR:1.543,95%CI:1.198-1.988) were positively associated, eGFR (OR:0.980,95%CI:0.970-0.991) was negatively associated with kidney stone recurrence. And multivariate logistic regression analysis suggested that Apo B (OR:11.028, 95%CI:3.917-31.047) and eGFR (OR:0.976, 95%CI:0.965-0.988) were the most significant factors. Then we calculated Ae index and analyzed it, the sensitivity was 74.26% and the specificity was 60.00%, higher than either individual variable. Its smoothed curve revealed a non-linear relationship between them with the inflection point of 9.16. And the OR on the left side of the inflection point was 1.574 (95% CI: 1.228-2.018), whereas the OR on the right side of the inflection point was 1.088 (95% CI: 1.007-1.177).ConclusionsAe index is an easily calculated and obtained index that has some predictive value for kidney stone recurrence in overweight and obese patients, which is of interest.
| S-EPMC10518111 | biostudies-literature
Project description:Non-invasive blood-based molecule markers are evaluated as promising biomarkers these days. Here we investigated the potential of cell-free circulating DNA Integrity (cfDI) as blood-based marker for the prediction of recurrence during the follow-up of breast cancer patients within a prospective study cohort. cfDI was determined in plasma of 212 individuals, by measuring ALU and LINE1 repetitive DNA elements using quantitative PCR. A significant decrease of cfDI in recurrent breast cancer patients was observed. The group of patients who had impending recurrence during the follow-up had significant lower cfDI compared to the group of non-recurrent patients (P < 0.001 for ALU and LINE1 cfDI). cfDI could differentiate recurrent breast cancer patients from non-recurrent breast cancer subjects (area under the curve, AUC = 0.710 for ALU and 0.704 for LINE1). Univariate and multivariate analysis confirmed a significant association of recurrence and cfDI. Breast cancer patients with a lower cfDI had a much higher risk to develop recurrence than the patients with a higher cfDI (P = 0.020 for ALU cfDI and P = 0.019 for LINE1 cfDI, respectively). Further we show that cfDI is an independent predictor of breast cancer recurrence. In combination with other molecular markers, cfDI might be a useful biomarker for the prediction for breast cancer recurrence in clinic utility. We propose that cfDI might also be useful for the prediction of recurrence during the follow-up of other cancers.
| S-EPMC5589601 | biostudies-literature
Project description:To validate a panel of methylation-based salivary rinse biomarkers (P16, CCNA1, DCC, TIMP3, MGMT, DAPK, and MINT31) previously shown to be independently associated with poor overall survival and local recurrence in a larger, separate cohort of patients with head and neck squamous cell carcinoma (HNSCC).One hundred ninety-seven patients were included. All pretreatment saliva DNA samples were evaluated for the methylation status of the gene promoters by quantitative methylation-specific PCR. The main outcome measures were overall survival, local recurrence-free survival, and disease-free survival.In univariate analyses, the detection of hypermethylation of CCNA1, MGMT, and MINT31 was significantly associated with poor overall survival; the detection of hypermethylation of TIMP3 was significantly associated with local recurrence-free survival; and the detection of hypermethylation of MINT31 was significantly associated with poor disease-free survival. In multivariate analyses, detection of hypermethylation at any single marker was not predictive of overall survival in patients with HNSCC; detection of hypermethylation of TIMP3 in salivary rinse had an independent, significant association with local recurrence-free survival (HR = 2.51; 95% CI: 1.10-5.68); and none of the studied markers was significantly associated with disease-free survival.The detection of promoter hypermethylation of the seven genes in salivary rinse as an independent prognostic indicator of overall survival in patients with HNSCC was not validated. Detection of promoter hypermethylation of TIMP3 in pretreatment salivary rinse is independently associated with local recurrence-free survival in patients with HNSCC and may be a valuable salivary rinse biomarker for HNSCC recurrence.
| S-EPMC3288549 | biostudies-literature
Project description:BackgroundBreast cancer in young women tends to have a natural history of aggressive disease for which rates of recurrence are higher than in breast cancers detected later in life. Little is known about the genetic pathways that underlie early-onset breast cancer. Here we report the discovery of DEAR1 (ductal epithelium-associated RING Chromosome 1), a novel gene encoding a member of the TRIM (tripartite motif) subfamily of RING finger proteins, and provide evidence for its role as a dominant regulator of acinar morphogenesis in the mammary gland and as an independent predictor of local recurrence-free survival in early-onset breast cancer.Methods and findingsSuppression subtractive hybridization identified DEAR1 as a novel gene mapping to a region of high-frequency loss of heterozygosity (LOH) in a number of histologically diverse human cancers within Chromosome 1p35.1. In the breast epithelium, DEAR1 expression is limited to the ductal and glandular epithelium and is down-regulated in transition to ductal carcinoma in situ (DCIS), an early histologic stage in breast tumorigenesis. DEAR1 missense mutations and homozygous deletion (HD) were discovered in breast cancer cell lines and tumor samples. Introduction of the DEAR1 wild type and not the missense mutant alleles to complement a mutation in a breast cancer cell line, derived from a 36-year-old female with invasive breast cancer, initiated acinar morphogenesis in three-dimensional (3D) basement membrane culture and restored tissue architecture reminiscent of normal acinar structures in the mammary gland in vivo. Stable knockdown of DEAR1 in immortalized human mammary epithelial cells (HMECs) recapitulated the growth in 3D culture of breast cancer cell lines containing mutated DEAR1, in that shDEAR1 clones demonstrated disruption of tissue architecture, loss of apical basal polarity, diffuse apoptosis, and failure of lumen formation. Furthermore, immunohistochemical staining of a tissue microarray from a cohort of 123 young female breast cancer patients with a 20-year follow-up indicated that in early-onset breast cancer, DEAR1 expression serves as an independent predictor of local recurrence-free survival and correlates significantly with strong family history of breast cancer and the triple-negative phenotype (ER(-), PR(-), HER-2(-)) of breast cancers with poor prognosis.ConclusionsOur data provide compelling evidence for the genetic alteration and loss of expression of DEAR1 in breast cancer, for the functional role of DEAR1 in the dominant regulation of acinar morphogenesis in 3D culture, and for the potential utility of an immunohistochemical assay for DEAR1 expression as an independent prognostic marker for stratification of early-onset disease.
| S-EPMC2673042 | biostudies-literature
Project description:Recent studies have provided conflicting data regarding the role of dyslipidemia in amyotrophic lateral sclerosis (ALS). The aim of this study was to determine whether cholesterol level are an independent predictor of survival in ALS.Cholesterol levels were measured in 427 ALS subjects from three clinical trial databases.The LDL/HDL ratio did not decrease over time, despite significant declines in body mass index (BMI), forced vital capacity (FVC), and ALSFRS-R. After adjusting for BMI, FVC, and age, the lipid ratio was not associated with survival. There was a "U"-shaped association between BMI and mortality, with the highest survival at 30-35 kg/m(2). The adjusted hazard ratio for the linear association between BMI and survival was 0.860 (95% CI 0.80-0.93, P = 0.0001).We found that dyslipidemia is not an independent predictor of survival in ALS. BMI is an independent prognostic factor for survival after adjusting for markers of disease severity.
| S-EPMC4441750 | biostudies-literature