bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computed Tomography-Based Radiomics Model for Predicting the WHO/ISUP Grade of Clear Cell Renal Cell Carcinoma Preoperatively: A Multicenter Study
Authors: Wang Ruihui , Hu Zhengyu , Shen Xiaoyong , Wang Qidong , Zhang Liang , Wang Minhong , Feng Zhan , Chen Feng 
Published: February 2021

PurposeTo examine the ability of computed tomography radiomic features in multivariate analysis and construct radiomic model for identification of the the WHO/ISUP pathological grade of clear cell renal cell carcinoma (ccRCC).MethodsThis was a retrospective study using data of four hospitals from January 2018 to August 2019. There were 197 patients with a definitive diagnosis of ccRCC by post-surgery pathology or biopsy. These subjects were divided into the training set (n = 122) and the independent external validation set (n = 75). Two phases of Enhanced CT images (corticomedullary phase, nephrographic phase) of ccRCC were used for whole tumor Volume of interest (VOI) plots. The IBEX radiomic software package in Matlab was used to extract the radiomic features of whole tumor VOI images. Next, the Mann–Whitney U test and minimum redundancy-maximum relevance algorithm(mRMR) was used for feature dimensionality reduction. Next, logistic regression combined with Akaike information criterion was used to select the best prediction model. The performance of the prediction model was assessed in the independent external validation cohorts. Receiver Operating Characteristic curve (ROC) was used to evaluate the discrimination of ccRCC in the training and independent external validation sets.ResultsThe logistic regression prediction model constructed with seven radiomic features showed the best performance in identification for WHO/ISUP pathological grades. The Area Under Curve (AUC) of the training set was 0.89, the sensitivity comes to 0.85 and specificity was 0.84. In the independent external validation set, the AUC of the prediction model was 0.81, the sensitivity comes to 0.58, and specificity was 0.95.ConclusionA radiological model constructed from CT radiomic features can effectively predict the WHO/ISUP pathological grade of CCRCC tumors and has a certain clinical generalization ability, which provides an effective value for patient prognosis and treatment.
A Weighted Gene Co-Expression Network Analysis–Derived Prognostic Model for Predicting Prognosis and Immune Infiltration in Gastric Cancer
Authors: Chen Qingchuan , Tan Yuen , Zhang Chao , Zhang Zhe , Pan Siwei , An Wen , Xu Huimian 
Published: February 2021

BackgroundGastric cancer (GC) is a major public health problem worldwide. In recent decades, the treatment of gastric cancer has improved greatly, but basic research and clinical application of gastric cancer remain challenges due to the high heterogeneity. Here, we provide new insights for identifying prognostic models of GC.MethodsWe obtained the gene expression profiles of GSE62254 containing 300 samples for training. GSE15459 and TCGA-STAD for validation, which contain 200 and 375 samples, respectively. Weighted gene co-expression network analysis (WGCNA) was used to identify gene modules. We performed Lasso regression and Cox regression analyses to identify the most significant five genes to develop a novel prognostic model. And we selected two representative genes within the model for immunohistochemistry staining with 105 GC specimens from our hospital to verify the prediction efficiency. Moreover, we estimated the correlation coefficient between our model and immune infiltration using the CIBERSORT algorithm. The data from GSE15459 and TCGA cohort validated the robustness and predictive accuracy of this prognostic model.ResultsOf the 12 gene modules identified, 1,198 green-yellow module genes were selected for further analysis. Multivariate Cox analysis was performed on genes from univariate Cox regression and Lasso regression analysis using the Cox proportional hazards regression model. Finally, we constructed a five gene prognostic model: Risk Score = [(-0.7547) * Expression (ARHGAP32)] + [(-0.8272) * Expression (KLF5)] + [1.09 * Expression (MAMLD1)] + [0.5174 * Expression (MATN3)] + [1.66 * Expression (NES)]. The prognosis of samples in the high-risk group was significantly poorer than that of samples in the low-risk group (p = 6.503e-11). The risk model was also regarded as an independent predictor of prognosis (HR, 1.678, p &lt; 0.001). The observed correlation with immune cells suggested that this risk model could potentially predict immune infiltration.ConclusionThis study identified a potential risk model for prognosis and immune infiltration prediction in GC using WGCNA and Cox regression analysis.
Glycemic Control as an Early Prognostic Marker in Advanced Pancreatic Cancer
Authors: Alpertunga Ipek , Sadiq Rabail , Pandya Deep , Lo Tammy , Dulgher Maxim , Evans Sarah , Bennett Bridget , Rennert Nancy , Frank Richard C. 
Published: February 2021

PurposeImpaired glucose metabolism is present in most patients with pancreatic ductal adenocarcinoma (PDAC). Whereas previous studies have focused on pre-treatment glycemic indices and prognosis in those with concomitant diabetes, the effects of glycemic control during chemotherapy treatment on prognosis, in patients with and without diabetes, have not been well characterized. We examined the relationship between early glycemic control and overall survival (OS) in a cohort of patients with advanced PDAC treated in a community setting.Patients and MethodsSeventy-three patients with advanced PDAC (38% with diabetes) receiving chemotherapy while participating in a biobanking clinical trial were included. Clinical characteristics and laboratory results during 1 year were obtained from the electronic medical record. Kaplan-Meier estimate, log-rank test and hazard ratios were computed to assess the effect of glycemic control on OS. The Cox proportional hazards regression model was applied to ascertain the significance of glycemic control with other survival variables.ResultsOne thousand four hundred eighteen random blood glucose (RBG) values were analyzed. In accord with previous findings, a 50% decline in the serum tumor marker CA 19-9 at any time was predictive of survival (P=0.0002). In univariate analysis, an elevated pre-treatment average RBG, 3-month average RBG (RBG-3) and the FOLFIRINOX regimen were associated with longer survival. Based on ROC analysis (AUC=0.82), an RBG-3 of 120 mg/dl was determined to be the optimal cutoff to predict 12-month survival. In multivariate analysis that included age, stage, BMI, performance status, presence of diabetes, and chemotherapy regimen, only RBG-3 maintained significance: an RBG-3 ≤120 mg/dl predicted for improved OS compared to &gt;120 mg/dl (19 vs. 9 months; HR=0.37, P=0.002). In contrast, an early decline in CA 19-9 could not predict OS.ConclusionLower glucose levels during the first 3 months of treatment for advanced PDAC predict for improved OS in patients both with and without diabetes. These results suggest that RBG-3 may be a novel prognostic biomarker worthy of confirmation in a larger patient cohort and that studies exploring a possible cause and effect of this novel survival-linked relationship are warranted.
Rab12 Promotes Radioresistance of HPV-Positive Cervical Cancer Cells by Increasing G2/M Arrest
Authors: Huang Yujie , Tian Yonghao , Zhang Wenhao , Liu Ruijuan , Zhang Weifang 
Published: February 2021

BackgroundHPV-positive (HPV+) cervical cancer cells are more radioresistant compared with HPV-negative (HPV-) cervical cancer cells, but the underlying mechanism is not fully illuminated. Our previous mass spectrometry data showed that Ras-associated binding protein Rab12 was up-regulated by HPV, and this study is to investigate the role of Rab12 in the radioresistance of HPV-positive cervical cancer cells.MethodsCCK-8 assay, colony formation assay, flow cytometry, and Western blot were performed to determine cell proliferation, apoptosis, cell cycle distribution, and protein expressions. DNA damage and repair levels were measured by comet assays and detection of γ-H2AX, XRCC4, and pBRCA1 protein expressions.ResultsRab12 mRNA and protein expressions were up-regulated in cervical cancer tissues and HPV+ cervical cancer cells. Knockdown of Rab12 enhanced radiosensitivity while overexpression of Rab12 promotes radioresistance. Knockdown of Rab12 alleviated G2/M arrest by decreasing p-Cdc2(Tyr15) after radiation, which was a result of the reduction of p-Cdc25C(Ser216). Rab12 knockdown caused more DNA double-strand breaks (DSBs) and inhibited DNA homologous recombination repair (HRR) after radiation. Instead, overexpression of Rab12 enhanced radioresistance by increasing G2/M arrest, which provided more time for DNA HRR.ConclusionsRab12 may serve as a potential therapeutic target to improve clinical treatment outcome of cervical cancer.
Nomograms to Predict the Density of Tumor-Infiltrating Lymphocytes in Patients With High-Grade Serous Ovarian Cancer
Authors: Dai Danian , Liu Lili , Huang He , Chen Shangqiu , Chen Bo , Cao Junya , Luo Xiaolin , Wang Feng , Luo Rongzhen , Liu Jihong 
Published: February 2021

BackgroundTumor-infiltrating lymphocytes (TILs) have important roles in predicting tumor therapeutic responses and progression, however, the method of evaluating TILs is complicated. We attempted to explore the association of TILs with clinicopathological characteristics and blood indicators, and to develop nomograms to predict the density of TILs in patients with high-grade serous ovarian cancer (HGSOC).MethodsThe clinical profiles of 197 consecutive postoperative HGSOC patients were retrospectively analyzed. Tumor tissues and matched normal fallopian tubes were immunostained for CD3+, CD8+, and CD4+ T cells on corresponding tissue microarrays and the numbers of TILs were counted using the NIH ImageJ software. The patients were classified into low- or high-density groups for each marker (CD3, CD4, CD8). The associations of the investigated TILs to clinicopathological characteristics and blood indicators were assessed and the related predictors for densities of TILs were used to develop nomograms; which were then further evaluated using the C-index, receiver operating characteristic (ROC) curves and calibration plots.ResultsMenopausal status, estrogen receptor (ER), Ki-67 index, white blood cell (WBC), platelets (PLT), lactate dehydrogenase (LDH), and carbohydrate antigen 153 (CA153) had significant association with densities of tumor-infiltrating CD3+, CD8+, or CD4+ T cells. The calibration curves of the CD3+ (C-index = 0.748), CD8+ (C-index = 0.683) and CD4+ TILs nomogram (C-index = 0.759) demonstrated excellent agreement between predictions and actual observations. ROC curves of internal validation indicated good discrimination for the CD8+ TILs nomogram [area under the curve (AUC) = 0.659, 95% CI 0.582–0.736] and encouraging performance for the CD3+ (AUC= 0.708, 95% CI 0.636–0.781) and CD4+ TILs nomogram (AUC = 0.730, 95% CI 0.659–0.801).ConclusionMenopausal status, ER, Ki-67 index, WBC, PLT, LDH, and CA153 could reflect the densities of T cells in the tumor microenvironment. Novel nomograms are conducive to monitor the immune status of patients with HGSOC and help doctors to formulate the appropriate treatment strategies.
Hepatic Arterial Infusion Chemotherapy Combined With PD-1 Inhibitors Plus Lenvatinib Versus PD-1 Inhibitors Plus Lenvatinib for Advanced Hepatocellular Carcinoma
Authors: Mei Jie , Tang Yu-Hao , Wei Wei , Shi Ming , Zheng Lie , Li Shao-Hua , Guo Rong-Ping 
Published: February 2021

BackgroundLenvatinib combined with programmed cell death protein-1 (PD-1) inhibitors has resulted in good survival outcomes in the treatment of unresectable hepatocellular carcinoma (HCC). Hepatic artery infusion chemotherapy (HAIC) has also attracted attention due to its high response rates and favorable survival for advanced HCC patients. The present study aimed to compare the efficacy of HAIC combined with PD-1 inhibitors plus lenvatinib (HPL) and PD-1 inhibitors plus lenvatinib (PL) in patients with advanced HCC.MethodsBetween July 2018 and December 2019, patients diagnosed with advanced HCC who initially received HPL or PL treatment were reviewed for eligibility. Efficacy was evaluated according to tumor response and survival.ResultsIn total, 70 patients met the criteria and were included in the present study, and they were divided into the HPL group (n = 45) and PL group (n = 25). The overall response rate (40.0 vs. 16.0%, respectively; p = 0.038) and disease control rate (77.6 vs. 44.0%, respectively; p &lt; 0.001) were higher in the HPL group than in the PL group. The median overall survival was 15.9 months in the HPL group and 8.6 months in the PL group (p = 0.0015; HR = 0.6; 95% CI 0.43–0.83). The median progression-free survival was 8.8 months in the HPL group and 5.4 months in the PL group (p = 0.0320; HR = 0.74; 95% CI 0.55–0.98).ConclusionCompared to PL, HPL was associated with a significantly better treatment response and survival benefits for patients with advanced HCC.
Comprehensive Analysis of Expression Regulation for RNA m6A Regulators With Clinical Significance in Human Cancers
Authors: Liu Xiaonan , Wang Pei , Teng Xufei , Zhang Zhang , Song Shuhui 
Published: February 2021

BackgroundN6-methyladenosine (m6A), the most abundant chemical modification on eukaryotic messenger RNA (mRNA), is modulated by three class of regulators namely “writers,” “erasers,” and “readers.” Increasing studies have shown that aberrant expression of m6A regulators plays broad roles in tumorigenesis and progression. However, it is largely unknown regarding the expression regulation for RNA m6A regulators in human cancers.ResultsHere we characterized the expression profiles of RNA m6A regulators in 13 cancer types with The Cancer Genome Atlas (TCGA) data. We showed that METTL14, FTO, and ALKBH5 were down-regulated in most cancers, whereas YTHDF1 and IGF2BP3 were up-regulated in 12 cancer types except for thyroid carcinoma (THCA). Survival analysis further revealed that low expression of several m6A regulators displayed longer overall survival times. Then, we analyzed microRNA (miRNA)-regulated and DNA methylation-regulated expression changes of m6A regulators in pan-cancer. In total, we identified 158 miRNAs and 58 DNA methylation probes (DMPs) involved in expression regulation for RNA m6A regulators. Furthermore, we assessed the survival significance of those regulatory pairs. Among them, 10 miRNAs and 7 DMPs may promote cancer initiation and progression; conversely, 3 miRNA/mRNA pairs in kidney renal clear cell carcinoma (KIRC) may exert tumor-suppressor function. These findings are indicative of their potential prognostic values. Finally, we validated two of those miRNA/mRNA pairs (hsa-miR-1307-3p/METTL14 and hsa-miR-204-5p/IGF2BP3) that could serve a critical role for potential clinical application in KIRC patients.ConclusionsOur findings highlighted the importance of upstream regulation (miRNA and DNA methylation) governing m6A regulators’ expression in pan-cancer. As a result, we identified several informative regulatory pairs for prognostic stratification. Thus, our study provides new insights into molecular mechanisms of m6A modification in human cancers.
The Effectiveness of Different Treatment Modalities of Cutaneous Angiosarcoma: Results From Meta-Analysis and Observational Data From SEER Database
Authors: Bi Siwei , Chen Shanshan , Wu Beiyi , Cen Ying , Chen Junjie 
Published: February 2021

IntroductionCutaneous angiosarcoma (cAS) is an aggressive vascular tumor that originates from vascular or lymphatic epithelial cells. To date, the cAS literature has been limited in a small number with single-center experiences or reports due to its rarity and the optimal treatment strategy is still in dispute. This study aimed to conduct a systematic review and compare the effect of available treatments retrieved from observational studies and Surveillance, Epidemiology, and End Results (SEER) program.MethodsThe authors performed a systematic review in the PubMed, Embase and MEDLINE database identifying the researches assessing the treatment for cAS patients. Clinical and treatment information of patients who had been diagnosed with a primary cAS were also obtained from the SEER program.ResultsThirty-two studies were eligible but only 5 of which with 276 patients were included in meta-analysis since the unclear or unavailable information. The risk ratio of 5-year death for surgery, surgery with radiotherapy and surgery with chemotherapy were 0.84, 0.96, and 0.69. Meanwhile, in SEER database, there are 291 metastatic and 437 localized patients with cAS. The localized patients receiving surgery showed a significantly worse overall survival result when compared with the surgery combined with RT: hazard ratio: 1.6, 95% confidential interval: 1.05, 2.42, P = 0.03.ConclusionIn conclusion, our study provided a detailed picture of the effectiveness of present treatments for localized and metastatic cAS patients. The CT could be inappropriate in localized patients. For metastatic patients, the surgery combined RT was recommended compared with surgery alone since its enhanced OS prognosis. Yet, more novel-designed clinical trials with specific targeted populations and rigorous conducting are needed for a solid conclusion on which would be a better treatment strategy.
Contralateral Lower Neck Sparing Radiotherapy in Stage N1 Nasopharyngeal Carcinoma: Long-Term Survival Outcomes and Late Toxicities
Authors: Sun Zhuang , Wang Jingyun , Huang Runda , Wang Xiaohui , Chen Chunyan , Deng Meiling , Zhao Chong , Wang Hanyu , Han Fei 
Published: February 2021

PurposeTo explore the feasibility of contralateral lower neck sparing radiotherapy for patients with stage N1 nasopharyngeal carcinoma (NPC) by analyzing long-term survival outcomes and late toxicities.MethodsData of patients with stage N1 NPC who were treated with contralateral lower neck sparing radiotherapy between January 2013 and December 2015 were analyzed. These patients were all staged by magnetic resonance imaging (MRI), and all received irradiation to the upper neck (levels II, III, and Va) bilaterally along with ipsilateral levels IV and Vb, without irradiation of the contralateral lower neck. Treatment outcomes, regional failure patterns, and late toxicities were examined.ResultsA total of 275 eligible patients with stage N1 NPC were included in the present study. The median follow-up period was 62 months (range, 3–93 months). The 5-year overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), locoregional recurrence-free survival (LRRFS), and progression-free survival (PFS) rates were 90.5, 91.3, 94.7, 95.3, 91.2, and 81.7%, respectively. A total of 13 patients (4.7%) developed regional recurrence, all of which occurred in the field and not out of the field. Among 254 patients with available data on late toxicities, the most common late toxicity was xerostomia. No late injuries occurred in the carotid arteries, brachial plexus, or spinal cord. In addition to one case (0.4%) of neck fibrosis and three cases (1.2%) of hearing loss, there were no other grade 3–4 late toxicities observed.ConclusionsContralateral lower neck sparing radiotherapy would be safe and feasible for patients with stage N1 NPC, with the potential to improve the long-term quality of life of patients.
Identification and Validation of Ubiquitin-Specific Proteases as a Novel Prognostic Signature for Hepatocellular Carcinoma
Authors: Ni Wenkai , Bian Saiyan , Zhu Mengqi , Song Qianqian , Zhang Jianping , Xiao Mingbing , Zheng Wenjie 
Published: February 2021

PurposeUbiquitin-specific proteases (USPs), as a sub-family of deubiquitinating enzymes (DUBs), are responsible for the elimination of ubiquitin-triggered modification. USPs are recently correlated with various malignancies. However, the expression features and clinical significance of USPs have not been systematically investigated in hepatocellular carcinoma (HCC).MethodsGenomic alterations and expression profiles of USPs were investigated in CbioPortal and The Cancer Genome Atlas (TCGA) Liver hepatocellular carcinoma (LIHC) dataset. Cox regression and least absolute shrinkage and selection operator (LASSO) analyses were conducted to establish a risk signature for HCC prognosis in TCGA LIHC cohort. Subsequently, Kaplan-Meier analysis, receiver operating characteristic (ROC) curves and univariate/multivariate analyses were performed to evaluate the prognostic significance of the risk signature in TCGA LIHC and international cancer genome consortium (ICGC) cohorts. Furthermore, we explored the alterations of the signature genes during hepatocarcinogenesis and HCC progression in GSE89377. In addition, the expression feature of USP39 was further explored in HCC tissues by performing western blotting and immunohistochemistry.ResultsGenomic alterations and overexpression of USPs were observed in HCC tissues. The consensus analysis indicated that the USPs-overexpressed sub-Cluster was correlated with aggressive characteristics and poor prognosis. Cox regression with LASSO algorithm identified a risk signature formed by eight USPs for HCC prognosis. High-risk group stratified by the signature score was correlated with advanced tumor stage and poor survival HCC patients in TCGA LIHC cohort. In addition, the 8-USPs based signature could also robustly predict overall survival of HCC patients in ICGC(LIRI-JP) cohort. Furthermore, gene sets enrichment analysis (GSEA) showed that the high-risk score was associated with tumor-related pathways. According to the observation in GSE89377, USP39 expression was dynamically increased with hepatocarcinogenesis and HCC progression. The overexpression of USP39 was further determined in a local HCC cohort and correlated with poor prognosis. The co-concurrence analysis suggested that USP39 might promote HCC by regulating cell-cycle- and proliferation- related genes.ConclusionThe current study provided a USPs-based signature, highlighting its robust prognostic significance and targeted value for HCC treatment.