Utility of a multigene testing for preoperative evaluation of indeterminate thyroid nodules: A prospective blinded single center study in China

xloma.fota13 shared this article with you from Inoreader Utility of a multigene testing for preoperative evaluation of indeterminate thyroid nodules: A prospective blinded single center study in China Via Cancer Medicine We introduced a multigene panal for cancer diagnosis in FNA‐indeterminate thyroid nodules, and evaluated its performance in Chinese population. Abstract Background Thyroid nodules are highly prevalent, with fine‐needle aspiration (FNA) commonly used as the standard preoperative tool for their diagnosis. However, the method classifies some of the samples as indeterminate, leading to unnecessary surgery. In this study, we evaluated the value of next‐generation sequencing (NGS) for cancer diagnosis in indeterminate thyroid nodules. Materials and methods We performed a prospective, blinded cohort study on 189 patients, with 196 Bethesda III/IV nodules. Specifically, we analyzed DNA mutations and RNA fusions across the FNA samples using NGS, then reviewed follow‐up reports from 84 nodules following definitive surgery, to determine the assay performance. Results Enough DNA and RNA were obtained in 188 nodules, revealing mutations or fusions in 34.6% of them. The most frequently mutated genes were RAS, followed by BRAF V600E. Based on surgical pathology, 39% (33/84) and 4.8% (4/84) of the nodules were malignant and intermediate, respectively. According to the risk stratification criteria, 28 cases were categorized High‐Risk group, all of the resected nodules (n = 20) were malignant. Twenty‐four thyroid nodules were in the Low‐Risk group, 28.6% (4/14) surgically removed nodules were malignant. In the Benign‐Like category, 18.0% (9/50) were malignant. Five out of 13 nodules with benign mutations were resected, including SPOP, EZH1, and ZNF148, all of them were benign. If genetic alterations annotated with High‐Risk or Low‐Risk was considered as positive, and negative if Benign‐Like. Multigene testing revealed sensitivity, specificity, positive predictive values (PPV), and negative predictive value (NPV) of 73%, 80%, 7 1%, and 82%, respectively. In addition, if four intermediate nodules were counted as malignant, the PPV and NPV were 71% and 74%. Conclusion Our results allow for further stratification of Bethesda III/IV thyroid nodules based on the risk of their malignancy. SPOP, EZH1, and ZNF148 mutations may be used as benign markers. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Develop a circular RNA–related regulatory network associated with prognosis of gastric cancer

xloma.fota13 shared this article with you from Inoreader Develop a circular RNA–related regulatory network associated with prognosis of gastric cancer Via Cancer Medicine Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment annotations of differentially expressed genes (DEGs) (up‐(A) and down (B)‐regulated DEGs). Abstract Background In gastric cancer (GC), circular RNAs (circRNAs) mainly play an important role in miRNA sponge, which not only indicate long‐term survival and prognosis but also increase resistance to the apoptosis. The purpose of the study is to explore new circRNAs and their underlying mechanisms in GC. Method Through rigorous retrieval strategies, we used the sva package to analyze and identify differentially expressed circRNAs (DECs) from three Gene Expression Omnibus microarray datasets (GSE83521, GSE89143, and GSE78092). Online website CSCD and CircInteractome were used to reveal the binding sites between miRNAs and DECs. The possible target miRNAs of the DECs identified based on miRNAs, and Cytoscape was used to create a regulatory network of circRNA‐m iRNA‐mRNA and identified the hub genes which were further validated using The Cancer Genome Atlas database and Human Protein Atlas. Results Twenty‐eight DECs were obtained using the sva package. A regulatory network of circRNA‐miRNA‐mRNA (competing endogenous RNA) containing 15 circRNAs, 24 miRNAs, and 158 genes was identified. A protein‐protein interaction network based on the 158 genes was established, and further determined that 10 hub genes (SKA1, ANLN, CHEK1, SKA3, TOP2A, BIRC5, RRM2, NCAPG2, FANCI, and RAD51) were associated with some cancer‐related pathways based on the functional enrichment analysis. Finally, six hub genes (BIRC5, TOP2A, FANCI, NCAPG2, RAD51, and RRM2) were proven to influence the overall survival of GC. Conclusion Our study established a circRNA‐miRNA‐mRNA regulatory network and defined six circRNA‐related hub genes in GC, which could serve as potential therapeutic targets or prognostic biomarker for GC treatment. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Health care‐related time costs in patients with metastatic breast cancer

xloma.fota13 shared this article with you from Inoreader Health care‐related time costs in patients with metastatic breast cancer Via Cancer Medicine In patients with metastatic breast cancer, time spent on health care ranged from 7% to 10% of all days included within the initial 3 months of treatment, depending on type of treatment received and its administration method. The greatest time contributions were time spent traveling for care and on inpatient services, and health care time was higher for patients receiving chemotherapeutic agents compared to those receiving hormonal agents. Abstract Background Burdens related to time spent receiving cancer care may be substantial for patients with incurable, life‐limiting cancers such as metastatic breast cancer (MBC). Estimates of time spent on health care are needed to inform treatment‐related decision‐making. Methods Estimates of time spent receiving cancer‐related health care in the initial 3 months of treatment for patients with MBC were calculated using the following data sources: (a) direct observations from a time‐in‐motion quality improvement evaluation (process mapping); (b) cross‐sectional patient surveys; and (c) administrative claims. Average ambulatory, inpatient, and total health care time were calculated for specific treatments which differed by antineoplastic type and administration method, including fulvestrant (injection, hormonal), letrozole (oral, hormonal), capecitabine (oral, chemotherapy), and paclitaxel (infusion, chemotherapy). Results Average total time spent on health care ranged from 7% to 10% of all days included within the initial 3 months of treatment, depending on treatment. The greatest time contributions were time spent traveling for care and on inpatient services. Time with providers contributed modestly to total care time. Patients receiving infusion/injection treatments, compared with those receiving oral therapy, spent more time in ambulatory care. Health care time was higher for patients receiving chemotherapeutic agents compared to those receiving hormonal agents. Conclusion Time spent traveling and receiving inpatient care represented a substantial burden to patients with MBC, with variation in time by treatment type and administration method. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Serum N‐Glycome analysis reveals pancreatic cancer disease signatures

xloma.fota13 shared this article with you from Inoreader Serum N‐Glycome analysis reveals pancreatic cancer disease signatures Via Cancer Medicine Serum protein glycosylation differences between pancreatic cancer patients and healthy individuals are discussed with regard to their potential to function as a diagnostic signature. Results were validated in an independent cohort and it was concluded that the serum N‐glycome analysis can serve as a basis for the development of a blood‐based diagnostic test for the detection of pancreatic cancer. Abstract Background &Aims Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer type with loco‐regional spread that makes the tumor surgically unresectable. Novel diagnostic tools are needed to improve detection of PDAC and increase patient survival. In this study we explore serum protein N‐glycan profiles from PDAC patients with regard to their applicability to serve as a disease biomarker panel. Methods Total serum N‐glycome analysis was applied to a discovery set (86 PDAC cases/84 controls) followed by independent validation (26 cases/26 controls) using in‐house collected serum specimens. Protein N‐glycan profiles were obtained using ultrahigh resolution mass spectrometry and included linkage‐specific sialic acid information. N‐glycans were relatively quantified and case‐control classification performance was evaluated based on glycosylation traits such as branching, fucosylation, and sialylation. Results In PDAC patients a higher level of branching (OR 6.19, P‐value 9.21 × 10−11) and (antenna)fucosylation (OR 13.27, P‐value 2.31 × 10−9) of N‐glycans was found. Furthermore, the ratio of α2,6‐ vs α2,3‐linked sialylation was higher in patients compared to healthy controls. A classification model built with three glycosylation traits was used for discovery (AUC 0.88) and independent validation (AUC 0.81), with sensitivity and specificity values of 0.85 and 0.71 for the discovery set and 0.75 and 0.72 for the validation set. Conclusion Serum N‐glycome analysis revealed glycosylation differences that allow classification of PDAC patients from healthy controls. It was demonstrated that glycosylation traits rather than single N‐glycan structures obtained in this clinical glycomics study can serve as a basis for further development of a blood‐based diagnostic test. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Impact of radiotherapy to the primary tumor on the efficacy of pembrolizumab for patients with advanced urothelial cancer: A preliminary study

xloma.fota13 shared this article with you from Inoreader Impact of radiotherapy to the primary tumor on the efficacy of pembrolizumab for patients with advanced urothelial cancer: A preliminary study Via Cancer Medicine Radiotherapy to the primary tumor was significantly associated with favourable therapeutic response and prognosis following pembrolizumab therapy in advanced urothelial cancer patients. Thus, radiotherapy to the primary tumor may enhance the efficacy of pembrolizumab, indicating the possibility that radiotherapy to the primary tumor in combination with pembrolizumab may be a promising therapeutic strategy for urothelial cancer. Abstract Radiotherapy plus immune checkpoint inhibitors can potentially induce synergistic antitumor immune responses. However, little clinical evidence is established regarding their combination therapy. Here, we aimed to assess whether radiotherapy to the primary tumor impacts on the efficacy of pembrolizumab in advanced urothelial cancer. We retrospectively reviewed 98 advanced urothelial cancer patients receiving pembrolizumab in a second‐ or later‐line setting using our multicenter cohort. Patients were categorized according to a history of radiotherapy to the primary tumor: patients previously exposed to radiotherapy to the primary tumor (Radiotherapy group, 17 patients [17%]) and those not (Nonradiotherapy group, 81 patients [83%]). The associations of radiotherapy to the primary tumor with objective response and survival were evaluated. The Radiotherapy group showed a significantly higher objective response ratio than did the Non‐radiotherapy group (65% vs 19%; P  < .001). The Radiotherapy group had a higher progression‐free survival rate compared with the Nonradiotherapy group (52% vs 28% at 12 months; P = .078), but statistical significance was not reached. The Radiotherapy group had a significantly higher overall survival rate compared with the Non‐radiotherapy group (77% vs 50% at 12 months; P = .025). From multivariate analysis, radiotherapy to the primary tumor was an independent predictor for longer overall survival (hazard ratio, 0.31; P = .032) along with Eastern Cooperative Oncology Group performance status ≤1 and the absence of visceral metastasis. Therefore, radiotherapy to the primary tumor may enhance the efficacy of pembrolizumab for patients with advanced urothelial cancer. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Age‐specific prevalence and determinants of depression in long‐term breast cancer survivors compared to female population controls

xloma.fota13 shared this article with you from Inoreader Age‐specific prevalence and determinants of depression in long‐term breast cancer survivors compared to female population controls Via Cancer Medicine Long‐term breast cancer survivors (5‐16 years post‐diagnosis) with recurrence reported significantly higher prevalence of mild/severe depression than disease‐free survivors and controls, but prevalence in disease‐free survivors and controls was comparable. Cancer recurrence, age, education, employment, income, living independently, and BMI were significant determinants of depression in breast cancer survivors. Abstract Background Depression is more prevalent in breast cancer (BC) survivors than in the general population. However, little is known about depression in long‐term survivors. Study objectives were: (1) to compare the age‐specific prevalence of depressive symptoms (a) in BC survivors vs female population controls, (b) in disease‐free BC survivors vs BC survivors with self‐reported recurrence vs controls, and (2) to explore determinants of depression in BC survivors. Methods About 3010 BC survivors (stage I‐III, 5‐16 years post‐diagnosis), and 1005 population controls were recruited in German multi‐regional population‐based studies. Depression was assessed by the Geriatric Depression Scale‐15. Prevalence of mild/severe and severe depression only were estimated via logistic regression, controlling for age and education. Multinomial logistic regression was used to explore determinants of mild and severe depression. Results Compared with population controls, BC survivors were more likely to report mild/severe depression (30.4% vs 23.8%, p = .0003), adjusted for age and education. At all age groups <80 years, prevalence of both mild/severe and severe depression only was significantly higher in BC survivors, while BC survivors ≥80 years reported severe depression less frequently than controls. BC survivors with recurrence reported significantly higher prevalence of mild/severe depression than disease‐free survivors and controls, but prevalence in disease‐free survivors and controls was comparable. Age, income, living independently, recurrence, and BMI were significant determinants of mild depression in BC survivors. Age, education, employment, income, recurrence, and BMI were significant determinants of severe depression. Conclusions Long‐term BC survivors <80 years report significantly higher prevalence of depressive symptoms than controls, which might be explained by recurrence and individual factors. The findings suggest that depression in BC survivors is common, and even more after BC recurrence. Clinicians should routinize screening and normalize referral to psychological care. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Molecular and immunological associations of elevated serum lactate dehydrogenase in metastatic melanoma patients: A fresh look at an old biomarker

xloma.fota13 shared this article with you from Inoreader Molecular and immunological associations of elevated serum lactate dehydrogenase in metastatic melanoma patients: A fresh look at an old biomarker Via Cancer Medicine The association between elevated serum lactate dehydrogenase (sLDH) and poor prognosis in metastatic melanoma patients is well‐established but poorly understood. Our multi‐omics analysis of multiple cohorts of patients with melanoma metastases identified no significant intratumoral molecular, immunological, or metabolic associations with sLDH, supporting that sLDH serves at least partially as a surrogate of tumor burden but not of adverse tumor features. ABSTRACT Elevated serum lactate dehydrogenase (sLDH) is associated with poor clinical outcomes in patients with stage IV metastatic melanoma (MM). It is currently unknown if sLDH elevation correlates with distinct molecular, metabolic, or immune features of melanoma metastases. The identification of such features may identify rational therapeutic strategies for patients with elevated sLDH. Thus, we obtained sLDH levels for melanoma patients with metastases who had undergone molecular and/or immune profiling. Our analysis of multi‐omics data from independent cohorts of melanoma metastases showed that elevated sLDH was not significantly associated with differences in immune cell infiltrate, point mutations, DNA copy number variations, promoter methylation, RNA expression, or protein expression in melanoma metastases. The only significant association observed for elevated sLDH was with the number of metastatic sites of disease. Our data support that sLDH correlates with disease burden, but not specific molecular or immunological phenotypes, in metastatic melanoma. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Resveratrol suppresses the growth and metastatic potential of cervical cancer by inhibiting STAT3Tyr705 phosphorylation

xloma.fota13 shared this article with you from Inoreader Resveratrol suppresses the growth and metastatic potential of cervical cancer by inhibiting STAT3Tyr705 phosphorylation Via Cancer Medicine Resveratrol inhibits growth and metastatic potential of cervical cancer in vivo and in vitro. Resveratrol inhibits phosphorylation of STAT3 at Tyr705 but not Ser727. Resveratrol Suppress growth and Epithelial Mesenchymal Transition of cervical cancer through inhibiting STAT3 Tyr705 phosphorylation. Abstract Aberrant signal transducer and activator of transcription 3 (STAT3) signaling promotes the initiation and progression of cancer in humans by either inhibiting apoptosis or inducing cell proliferation, angiogenesis, invasion, and metastasis. The role of resveratrol（RES）in inhibiting the STAT3 signaling pathway in vivo, particularly in cervical cancer is still unknown. This study aims to investigate the role of STAT3 and its phosphorylation in RES‐mediated suppression of cervical cancer. The effects of RES on cervical cancer were determined by examining tumor tissues, their histological changes, and the volume and weight of tumor tissues grown from HeLa cells injected in female athymic BALB/C nude mice. The structure and target interaction of RES were virtually screened using the molecular docking program Autodock Vina. The status of phosphorylated STAT3, protein levels of epithelial‐mesenchymal transition molecular markers and extracellular matrix degradation enzymes were determined through Western blot. We demonstrated that RES could suppress the proliferation and metastatic potential of cervical cancer cells by inactivating phosphorylation of STAT3 at Tyr705 but not Ser727. This effect was intensified by inhibition of the STAT3 signal pathway. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Comprehensive analysis on the expression levels and prognostic values of LOX family genes in kidney renal clear cell carcinoma

xloma.fota13 shared this article with you from Inoreader Comprehensive analysis on the expression levels and prognostic values of LOX family genes in kidney renal clear cell carcinoma Via Cancer Medicine We firstly comprehensively explored the role of LOX family genes in kidney renal clear cell carcinoma, and found that LOX and LOXL2 may be used as new therapeutic targets for kidney renal clear cell carcinoma. Abstract Backgrounds Kidney renal clear cell carcinoma (KIRC) is a major pathological type of renal cell carcinoma (RCC), and the prognosis of advanced KIRC patients is often unsatisfactory. Some lysine oxidase (LOX) family genes have been proven to be upregulated in some malignancies and play pivotal roles in the carcinogenesis. However, their roles in KIRC remain unclear. Materials and Methods Here, we used some online databases (eg, ONCOMINE, GEPIA, UALCAN, c‐BioPortal, Human Protein Altas) to comprehensively explored the expression levels and the prognostic values of LOX family genes in KIRC using bioinformatic methods. Results The results revealed that lysyl oxidase (LOX) and lysyl oxidase‐like 2 (LOXL2) were significantly overexpressed in KIRC at the level of mRNA expression, protein expression, and RCC cell lines. Further analysis demonstrated that higher mRNA expression of LOX and LOXL2 were significantly correlated with poor survival, tumor grade, individual cancer stages, and nodal metastasis status. DNA copy number amplifications and mRNA upregulation, DNA deep deletion, and mRNA upregulation were the main genetic mutations of LOX and LOXL2, respectively. Prognostic analysis showed that the altered group had significantly poorer overall survival (OS) compared to the unaltered group (p = .0387). Co‐expression analysis showed CP, PLOD2, and COL5A1 were significantly correlated with LOX, and COL1A2 was positively correlated with LOXL2. Further analysis confirmed that these co‐expressed genes were significantl y upregulated and predicted unfavorable prognosis in KIRC. Conclusion Multi‐level analysis demonstrated that LOX and LOXL2 were significantly upregulated and predicted poor survival in KIRC, which may apply as promising biomarkers for diagnosis and therapy of KIRC in the future. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Correlation of tumor‐infiltrating immune cells of melanoma with overall survival by immunogenomic analysis

xloma.fota13 shared this article with you from Inoreader Correlation of tumor‐infiltrating immune cells of melanoma with overall survival by immunogenomic analysis Via Cancer Medicine Immunotherapy has shown excellent responses in melanoma, while the reaction is low. However, the molecular mechanisms of tumor infiltrated immune cells have not been explored. In this study, we found that higher ESTIMATE and immune scores were associated with a clinical‐stage in melanoma patients and also filtered the crosstalks between cells that immune cells. Our work revealed the immune cellular and molecular characteristics of melanoma, providing a method for selecting targets promoting immunotherapy efficacy. Abstract Aims Different types of tumor‐infiltrating immune cells not only augment but also dampen antitumor immunity in the microenvironment of melanoma. Therefore, it is critical to provide an overview of tumor‐infiltrating immune cells in melanoma and explore a novel strategy for immunotherapies. Methods We analyzed the immune states of different stages in melanoma patients by the immune, stromal, and estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE) scores. Immune cell types were identified by the estimating relative subsets of RNA transcripts (CIBERSORTx) algorithm in 471 melanoma and 324 healthy tissues. Moreover, we performed a gene set variation analysis (GSVA) to determine the differentially regulated pathways in the tumor microenvironment. Results In melanoma cohorts, we found that ESTIMATE and immune scores were involved in survival or tumor clinical stage. Among the 22 immune cells, CD8+ T cells, M2 macrophages, and regulatory T cells (Tregs) showed significant differences using the CIBERSORTx algorithm. Furthermore, GSVA identified the immune cell‐related pathways; the primary immunodeficiency pathway, intestinal immune network for IgA, and TGF‐β pathways were identified as participants of the crosstalk in CD8+ T cells, Tregs, and M2 macrophages in the melanoma microenvironment. Conclusion These results reveal the cellular and molecular characteristics of immune cells in melanoma, providing a method for selecting targets of immunotherapies and promoting the efficacy of therapies for the treatment of melanoma. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.