Dataset Information

Variants in autophagy-related genes and clinical characteristics in melanoma: a population-based study.

ABSTRACT: Autophagy has been linked with melanoma risk and survival, but no polymorphisms in autophagy-related (ATG) genes have been investigated in relation to melanoma progression. We examined five single-nucleotide polymorphisms (SNPs) in three ATG genes (ATG5; ATG10; and ATG16L) with known or suspected impact on autophagic flux in an international population-based case-control study of melanoma. DNA from 911 melanoma patients was genotyped. An association was identified between (GG) (rs2241880) and earlier stage at diagnosis (OR 0.47; 95% Confidence Intervals (CI) = 0.27-0.81, P = 0.02) and a decrease in Breslow thickness (P = 0.03). The ATG16L heterozygous genotype (AG) (rs2241880) was associated with younger age at diagnosis (P = 0.02). Two SNPs in ATG5 were found to be associated with increased stage (rs2245214 CG, OR 1.47; 95% CI = 1.11-1.94, P = 0.03; rs510432 CC, OR 1.84; 95% CI = 1.12-3.02, P = 0.05). Finally, we identified inverse associations between ATG5 (GG rs2245214) and melanomas on the scalp or neck (OR 0.20, 95% CI = 0.05-0.86, P = 0.03); ATG10 (CC) (rs1864182) and brisk tumor infiltrating lymphocytes (TILs) (OR 0.42; 95% CI = 0.21-0.88, P = 0.02), and ATG5 (CC) (rs510432) with nonbrisk TILs (OR 0.55; 95% CI = 0.34-0.87, P = 0.01). Our data suggest that ATG SNPs might be differentially associated with specific host and tumor characteristics including age at diagnosis, TILs, and stage. These associations may be critical to understanding the role of autophagy in cancer, and further investigation will help characterize the contribution of these variants to melanoma progression.

SUBMITTER: White KA

PROVIDER: S-EPMC5119988 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Variants in autophagy-related genes and clinical characteristics in melanoma: a population-based study.

White Kirsten A M KA Luo Li L Thompson Todd A TA Torres Salina S Hu Chien-An Andy CA Thomas Nancy E NE Lilyquist Jenna J Anton-Culver Hoda H Gruber Stephen B SB From Lynn L Busam Klaus J KJ Orlow Irene I Kanetsky Peter A PA Marrett Loraine D LD Gallagher Richard P RP Sacchetto Lidia L Rosso Stefano S Dwyer Terence T Cust Anne E AE Begg Colin B CB Berwick Marianne M

Cancer medicine 20161017 11

Autophagy has been linked with melanoma risk and survival, but no polymorphisms in autophagy-related (ATG) genes have been investigated in relation to melanoma progression. We examined five single-nucleotide polymorphisms (SNPs) in three ATG genes (ATG5; ATG10; and ATG16L) with known or suspected impact on autophagic flux in an international population-based case-control study of melanoma. DNA from 911 melanoma patients was genotyped. An association was identified between (GG) (rs2241880) and ea ...[more]

PMID: 27748080

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Project description:BackgroundAutophagy, a highly conserved lysosomal degradation pathway, is associated with the prognosis of melanoma. However, prognostic prediction models based on autophagy related genes (ARGs) have never been recognized in melanoma. In the present study, we aimed to establish a novel nomogram to predict the prognosis of melanoma based on ARGs signature and clinical parameters.MethodsData from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases were extracted to identify the differentially expressed ARGs. Univariate, least absolute shrinkage and selection operator (LASSO) and multivariate analysis were used to select the prognostic ARGs. ARGs signature, age and stage were then enrolled to establish a nomogram to predict the survival probabilities of melanoma. The nomogram was evaluated by concordance index (C-index), receiver operating characteristic (ROC) curve and calibration curve. Decision curve analysis (DCA) was performed to assess the clinical benefits of the nomogram and TNM stage model. The nomogram was validated in GEO cohorts.ResultsFive prognostic ARGs were selected to construct ARGs signature model and validated in the GEO cohort. Kaplan-Meier survival analysis suggested that patients in high-risk group had significantly worse overall survival than those in low-risk group in TCGA cohort (P = 5.859 × 10-9) and GEO cohort (P = 3.075 × 10-9). We then established and validated a novel promising prognostic nomogram through combining ARGs signature and clinical parameters. The C-index of the nomogram was 0.717 in TCGA training cohort and 0.738 in GEO validation cohort. TCGA/GEO-based ROC curve and decision curve analysis (DCA) demonstrated that the nomogram was better than traditional TNM staging system for melanoma prognosis.ConclusionWe firstly developed and validated an ARGs signature based-nomogram for individualized prognosis prediction in melanoma patients, which could assist with decision making for clinicians.

Project description:Colonoscopy provides incomplete protection from colorectal cancer (CRC), but determinants of post-colonoscopy CRC are not well understood. We compared clinical features and molecular characteristics of CRCs diagnosed at different time intervals after a previous colonoscopy.We performed a population-based, cross-sectional study of incident CRC cases in Denmark (2007-2011), categorized as post-colonoscopy or detected during diagnostic colonoscopy (in patients with no prior colonoscopy). We compared prevalence of proximal location and DNA mismatch repair deficiency (dMMR) in CRC tumors, relative to time since previous colonoscopy, using logistic regression and cubic splines to assess temporal variation.Of 10,365 incident CRCs, 725 occurred after colonoscopy examinations (7.0%). These were more often located in the proximal colon (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.90-2.89) and were more likely to have dMMR (OR, 1.26; 95% CI, 1.00-1.59), but were less likely to be metastatic at presentation (OR, 0.65; 95% CI, 0.48-0.89) compared with CRCs diagnosed in patients with no prior colonoscopy. The highest proportions of proximal and/or dMMR tumors were observed in CRCs diagnosed 3-6 years after colonoscopy, but these features were still more frequent among cancers diagnosed up to 10 years after colonoscopy. The relative excess of dMMR tumors was most pronounced in distal cancers. In an analysis of 85 cases detected after colonoscopy, we found BRAF mutations in 23% of tumors and that 7% of cases had features of Lynch syndrome. Colonoscopy exams were incomplete in a higher proportion of cases diagnosed within <1 year (in 38%) than in those diagnosed within 1-10 years after colonoscopy (16%).In a study of incident CRC cases in Denmark, we observed that tumors found in patients who have undergone colonoscopy are more often proximal and have dMMR compared to CRCs detected in patients without previous colonoscopies. The excess of right-sided tumors and the modest independent effects of dMMR reinforce the importance of proper colonoscopic examination of the proximal large bowel.

Project description:ObjectivesTo study clinical characteristics and factors that may affect the prognosis of testicular sarcoma patients.Patients and methodsIn the Surveillance Epidemiology and End Results database (2006-2016), people with testicular sarcoma were enrolled in our research. Multivariable Cox proportional hazard model and Multivariable Logistic regression model were used to compare the impact of different factors on cancer-specific survival, localized metastasis, and distant metastasis.ResultsThis research was based on the registry information of 158 testicular sarcoma patients. All patients with a median age of 17.00 (1.00-93.00) years were pathologically diagnosed with orchiectomy or needle biopsy specimens. Patients with Grade I, II, III, and IV testicular sarcoma accounted for 34.29% (n = 24), 10.10% (n = 7), 22.86% (n = 16), and 32.86% (n = 23) of all patients, respectively. There were 42 (30.43%), 53 (38.41%), 15 (10.87%), 20 (14.49%), 5 (3.62%), 3 (2.17%) patients with Tis, T1, T2, T3, T4, and >T4 (the invasion degree exceeded the staging system of testicular cancer) disease respectively. Among all included patients, localized metastasis occurred in 31 (20.13%) patients, distant metastasis was found in 28 (18.18%) patients during observation, and 61.69% (n = 95) had no metastasis. Thirty-two (20.25%) patients died of this cancer. According to our study, patients with distant metastasis [OR = 17.86, 95% CI (4.63-68.84), p < 0.0001] and T3 disease [OR = 4.13, 95% CI (1.10-15.53), p = 0.0359] were more likely to die of this cancer. Patients with advanced T stage were more likely to occur distant metastasis, [OR = 13.91, 95% CI (1.80-107.54), p = 0.0116] for T3 and [OR = 16.36, 95% CI (1.36-196.21), p = 0.0275] for T4.ConclusionsAccording to our research, factors including metastasis and higher T stage were significantly related with poorer prognosis of testicular sarcoma. Higher T stage was also found to be a risk factor of distant metastasis. The recognization of these poor prognostic factors may allow physicians to make comprehensive and appropriate management decision for testicular sarcoma patients.

Project description:BackgroundPrevious studies reported cutaneous melanoma in head and neck (HNM) differed from those in other regions (body melanoma, BM). Individualized tools to predict the survival of patients with HNM or BM remain insufficient. We aimed at comparing the characteristics of HNM and BM, developing and validating nomograms for predicting the survival of patients with HNM or BM.MethodsThe information of patients with HNM or BM from 2004 to 2015 was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The HNM group and BM group were randomly divided into training and validation cohorts. We used the Kaplan-Meier method and multivariate Cox models to identify independent prognostic factors. Nomograms were developed via the rms and dynnom packages, and were measured by the concordance index (C-index), the area under the curve (AUC) of the receiver operating characteristic (ROC) curve and calibration plots.ResultsOf 70,605 patients acquired, 21% had HNM and 79% had BM. The HNM group contained more older patients, male sex and lentigo maligna melanoma, and more frequently had thicker tumors and metastases than the BM group. The 5-year cancer-specific survival (CSS) and overall survival (OS) rates were 88.1 ± 0.3% and 74.4 ± 0.4% in the HNM group and 92.5 ± 0.1% and 85.8 ± 0.2% in the BM group, respectively. Eight variables (age, sex, histology, thickness, ulceration, stage, metastases, and surgery) were identified to construct nomograms of CSS and OS for patients with HNM or BM. Additionally, four dynamic nomograms were available on web. The internal and external validation of each nomogram showed high C-index values (0.785-0.896) and AUC values (0.81-0.925), and the calibration plots showed great consistency.ConclusionsThe characteristics of HNM and BM are heterogeneous. We constructed and validated four nomograms for predicting the 3-, 5- and 10-year CSS and OS probabilities of patients with HNM or BM. These nomograms can serve as practical clinical tools for survival prediction and individual health management.

Dataset Information

Variants in autophagy-related genes and clinical characteristics in melanoma: a population-based study.

Publications

Variants in autophagy-related genes and clinical characteristics in melanoma: a population-based study.

Similar Datasets

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