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2022 ◽  
Vol 12 ◽  
Author(s):  
Guoda Song ◽  
Yucong Zhang ◽  
Hao Li ◽  
Zhuo Liu ◽  
Wen Song ◽  
...  

Background: Ubiquitin and ubiquitin-like (UB/UBL) conjugations are one of the most important post-translational modifications and involve in the occurrence of cancers. However, the biological function and clinical significance of ubiquitin related genes (URGs) in prostate cancer (PCa) are still unclear.Methods: The transcriptome data and clinicopathological data were downloaded from The Cancer Genome Atlas (TCGA), which was served as training cohort. The GSE21034 dataset was used to validate. The two datasets were removed batch effects and normalized using the “sva” R package. Univariate Cox, LASSO Cox, and multivariate Cox regression were performed to identify a URGs prognostic signature. Then Kaplan-Meier curve and receiver operating characteristic (ROC) curve analyses were used to evaluate the performance of the URGs signature. Thereafter, a nomogram was constructed and evaluated.Results: A six-URGs signature was established to predict biochemical recurrence (BCR) of PCa, which included ARIH2, FBXO6, GNB4, HECW2, LZTR1 and RNF185. Kaplan-Meier curve and ROC curve analyses revealed good performance of the prognostic signature in both training cohort and validation cohort. Univariate and multivariate Cox analyses showed the signature was an independent prognostic factor for BCR of PCa in training cohort. Then a nomogram based on the URGs signature and clinicopathological factors was established and showed an accurate prediction for prognosis in PCa.Conclusion: Our study established a URGs prognostic signature and constructed a nomogram to predict the BCR of PCa. This study could help with individualized treatment and identify PCa patients with high BCR risks.


2022 ◽  
Vol 11 ◽  
Author(s):  
Yiqun Li ◽  
Nilupai Abudureheiyimu ◽  
Hongnan Mo ◽  
Xiuwen Guan ◽  
Shaoyan Lin ◽  
...  

BackgroundTo characterize the clinical and pathological features and survival of patients with human epidermal growth factor receptor 2 (HER2)-low breast cancer in China.MethodsThe China National Cancer Center database was used to identify 1,433 metastatic breast cancer patients with HER2-negative disease diagnosed between 2005 and 2015. Clinicopathological features, survival, and prognosis information were extracted. Overall survival (OS) was estimated using the Kaplan–Meier method and compared using the log-rank test. Prognostic factors associated with OS were analyzed using Cox regression model with 95% confidence interval (95% CI).ResultsThere were 618 (43.1%) and 815 (56.9%) HER2-low and HER2-zero tumors out of 1,433 tumors, respectively. The proportion of hormone receptor (HR)-positive tumors was significantly higher in HER2-low tumors than in those with HER2-zero tumors (77.8% vs. 69.2%, p < 0.001). Patients with HER2-low tumors survived significantly longer than those with HER2-zero tumors in the overall population (48.5 months vs. 43.0 months, p = 0.004) and HR-positive subgroup (54.9 months vs. 48.1 months, p = 0.011), but not in the HR-negative subgroup (29.5 months vs. 29.9 months, p = 0.718). Multivariate regression analysis revealed that HER2-low tumors were independently associated with increased OS in HER2-negative population (HR: 0.85, 95% CI: 0.73–0.98, p = 0.026).ConclusionOur findings demonstrate that HER2-low tumors could be identified as a more distinct clinical entity from HER2-zero tumors, especially for the HR-positive subgroup. A more complex molecular landscape of HER2-low breast cancer might exist, and more precise diagnostic algorithms for HER2 testing could be investigated, thus offering new therapeutic targets for breast cancer treatment.


2022 ◽  
Vol 12 ◽  
Author(s):  
Yichun Guan ◽  
Pingping Kong ◽  
Zhiying Xiao ◽  
Junyan Zhang ◽  
Jingfang He ◽  
...  

ObjectiveTo assess whether women of advanced age (≥35 years) with polycystic ovary syndrome (PCOS) have the same cumulative live birth rate (CLBR) as their age-matched controls with tubal factor infertility and to determine the influencing factors on the CLBRs of aged women.DesignA retrospective cohort study.Setting and PopulationA total of 160 women of advanced age (≥35 years) with PCOS and 1073 women with tubal factor infertility were included in our study. All patients underwent their first fresh cycles and subsequent frozen cycles within in one year in our centre from 2015 to 2020.MethodsTo determine independent influencing factors on the CLBRs of these aged patients, a multivariable Cox regression model of CLBR according to the transfer cycle type was constructed. Main outcome measure(s): CLBRs.ResultThe Cox regression model of the CLBRs indicated that there was no significant difference between the PCOS group and the tubal infertility group in terms of advanced age (HR, 0.95; 95% CI, 0.71-1.27, P=0.732). The CLBR significantly decreased for women of advanced reproductive age up to 37 years of age (HR, 0.46; 95% CI, 0.39-0.56, P<0.001). The CLBR increased by 63% when more than ten oocytes were retrieved (HR, 1.63; 95% CI, 1.34-1.98, P<0.001). Patients with an AMH level above 32.13pmol/l were likely to have a 72%(HR, 1.72; 95% CI, 1.08-2.73, = 0.023) and 34% (HR, 1.34; 95% CI, 1.07-1.68, P=0.010)improvement in CLBR compared to those with an AMH below 7.85pmol/l and 7.85-32.12pmol/l, respectively.ConclusionDespite the higher number of oocytes retrieved in PCOS patients, the reproductive window is not extended for PCOS patients compared with tubal factor infertility patients. Age, AMH and the number of oocytes retrieved play crucial roles in the CLBRs of patients of advanced age (≥35 years).


Author(s):  
Mira Lanki ◽  
Hanna Seppänen ◽  
Harri Mustonen ◽  
Aino Salmiheimo ◽  
Ulf-Håkan Stenman ◽  
...  

Abstract Background For prognostic evaluation of pancreatic ductal adenocarcinoma (PDAC), the only well-established serum marker is carbohydrate antigen CA19-9. To improve the accuracy of survival prediction, we tested the efficacy of inflammatory serum markers. Methods A preoperative serum panel comprising 48 cytokines plus high-sensitivity CRP (hs-CRP) was analyzed in 173 stage I–III PDAC patients. Analysis of the effect of serum markers on survival utilized the Cox regression model, with the most promising cytokines chosen with the aid of the lasso method. We formed a reference model comprising age, gender, tumor stage, adjuvant chemotherapy status, and CA19-9 level. Our prognostic study model incorporated these data plus hs-CRP and the cytokines. We constructed time-dependent ROC curves and calculated an integrated time-averaged area under the curve (iAUC) for both models from 1 to 10 years after surgery. Results Hs-CRP and the cytokines CTACK, MIF, IL-1β, IL-3, GRO-α, M-CSF, and SCF, were our choices for the prognostic study model, in which the iAUC was 0.837 (95% CI 0.796–0.902), compared to the reference model’s 0.759 (95% CI 0.691–0.836, NS). These models divided the patients into two groups based on the maximum value of Youden’s index at 7.5 years. In our study model, 60th percentile survival times were 4.5 (95% CI 3.7–NA) years (predicted high-survival group, n = 34) and 1.3 (95% CI 1.0–1.7) years (predicted low-survival group, n = 128), log rank p < 0.001. By the reference model, the 60th percentile survival times were 2.8 (95% CI 2.1–4.4) years (predicted high-survival group, n = 44) and 1.3 (95% CI 1.0–1.7) years (predicted low-survival group, n = 118), log rank p < 0.001. Conclusion Hs-CRP and the seven cytokines added to the reference model including CA19-9 are potential prognostic factors for improved survival prediction for PDAC patients.


2022 ◽  
Author(s):  
Iyad Sultan ◽  
Abdelghani Tbakhi ◽  
Osama Abuatta ◽  
Sawsan Mubarak ◽  
Osama Alsmadi ◽  
...  

BACKGROUND: We aimed to assess the efficacy of 3 COVID-19 vaccines in a population of health care workers at a tertiary cancer center in Amman, Jordan. METHODS: We evaluated the records of 2855 employees who were fully vaccinated with 1 of 3 different vaccines and those of 140 employees who were not vaccinated. We measured the number of SARS-CoV-2 infections that occurred at least 14 days after the second vaccine dose. RESULTS The 100-day cumulative incidence of PCR-confirmed SARS-CoV-2 infections was 19.3% +/- 3.3% for unvaccinated employees and 1.7% +/- 0.27% for fully vaccinated employees. The 100-day cumulative infection rates were 0.7% +/- 0.22% in BNT162b2 vaccine recipients (n = 1714), 3.6% +/- 0.77% in BBIBP-CorV recipients (n = 680), and 2.3% +/- 0.73% in ChAdOx1 recipients (n = 456). We used Cox regression analyses to compare the risks of SARS-CoV-2 infection among the different vaccine recipient groups and found a significantly higher infection risk in BBIBP-CorV (hazard ratio [HR] = 2.9 +/- 0.31) and ChAdOx1 recipients (HR = 3.0 +/- 0.41) compared to BNT162b2 recipients (P = .00039 and .0074, respectively). Vaccinated employees who had no previously confirmed SARS-CoV-2 infections were at a markedly higher risk for breakthrough infections than those who experienced prior infections (HR = 5.7 +/- 0.73, P = .0178). CONCLUSIONS: Our study offers a real-world example of differential vaccine efficacy among a high-risk population during a national outbreak. We also show the important synergism between a previous SARS-CoV-2 infection and vaccination.


2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Dandan Guo ◽  
Huifang Wang ◽  
Jun Liu ◽  
Hang Liu ◽  
Ming Zhang ◽  
...  

Abstract Background We aimed to develop and validate a nomogram model for predicting CKD after orthotopic liver transplantation (OLT). Methods The retrospective data of 399 patients who underwent transplantation and were followed in our centre were collected. They were randomly assigned to the training set (n = 293) and validation set (n = 106). Multivariable Cox regression analysis was performed in the training set to identify predictors of CKD. According to the Cox regression analysis results, a nomogram model was developed and validated. The renal function of recipients was monitored, and the long-term survival prognosis was assessed. Results The incidence of CKD at 5 years after OLT was 25.6%. Cox regression analysis identified several predictors of post-OLT CKD, including recipient age at surgery (HR 1.036, 95% CI 1.006-1.068; p = 0.018), female sex (HR 2.867, 95% CI 1.709-4.810; p < 0.001), preoperative hypertension (HR 1.670, 95% CI 0.962-2.898; p = 0.068), preoperative eGFR (HR 0.996, 95% CI 0.991-1.001; p = 0.143), uric acid at 3 months (HR 1.002, 95% CI 1.001-1.004; p = 0.028), haemoglobin at 3 months (HR 0.970, 95% CI 0.956-0.983; p < 0.001), and average concentration of cyclosporine A at 3 months (HR 1.002, 95% CI 1.001-1.003; p < 0.001). According to these parameters, a nomogram model for predicting CKD after OLT was constructed and validated. The C-indices were 0.75 and 0.80 in the training and validation sets. The calibration curve of the nomogram showed that the CKD probabilities predicted by the nomogram agreed with the observed probabilities at 1, 3, and 5 years after OLT (p > 0.05). Renal function declined slowly year by year, and there were significant differences between patients divided by these predictors. Kaplan-Meier survival analysis showed that the survival prognosis of recipients decreased significantly with the progression of renal function. Conclusions With excellent predictive abilities, the nomogram may be a simple and reliable tool to identify patients at high risk for CKD and poor long-term prognosis after OLT.


2022 ◽  
Vol 2022 ◽  
pp. 1-10
Author(s):  
Tengfei Zhang ◽  
Yaxuan Wang ◽  
Yiming Dong ◽  
Lei Liu ◽  
Yikai Han ◽  
...  

Prostate cancer is still a significant global health burden in the coming decade. Novel biomarkers for detection and prognosis are needed to improve the survival of distant and advanced stage prostate cancer patients. The tumor microenvironment is an important driving factor for tumor biological functions. To investigate RNA prognostic biomarkers for prostate cancer in the tumor microenvironment, we obtained relevant data from The Cancer Genome Atlas (TCGA) database. We used the bioinformatics tools Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) algorithm and weighted coexpression network analysis (WGCNA) to construct tumor microenvironment stromal-immune score-based competitive endogenous RNA (ceRNA) networks. Then, the Cox regression model was performed to screen RNAs associated with prostate cancer survival. The differentially expressed gene profile in tumor stroma was significantly enriched in microenvironment functions, like immune response, cancer-related pathways, and cell adhesion-related pathways. Based on these differentially expressed genes, we constructed three ceRNA networks with 152 RNAs associated with the prostate cancer tumor microenvironment. Cox regression analysis screened 31 RNAs as the potential prognostic biomarkers for prostate cancer. The most interesting 8 prognostic biomarkers for prostate cancer included lncRNA LINC01082, miRNA hsa-miR-133a-3p, and genes TTLL12, PTGDS, GAS6, CYP27A1, PKP3, and ZG16B. In this systematic study for ceRNA networks in the tumor environment, we screened out potential biomarkers to predict prognosis for prostate cancer. Our findings might apply a valuable tool to improve prostate cancer clinical management and the new target for mechanism study and therapy.


Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 432
Author(s):  
Joohyun Woo ◽  
Hyungju Kwon

Multifocality increases the risk of recurrence in patients with papillary thyroid carcinoma (PTC); however, it is unclear whether multifocality justifies more extensive or aggressive surgical treatment. Here, we evaluated the effect of the operative extent on the recurrence-free survival (RFS) of patients with multifocal PTC. Between 2010 and 2019, 718 patients with unilateral multifocal PTC were enrolled; 115 patients (16.0%) underwent ipsilateral thyroid lobectomy, and 606 patients (84.0%) underwent total thyroidectomy. With a mean follow up of 5.2 years, RFS was comparable between the total thyroidectomy and lobectomy groups (p = 0.647) after adjusting for potential confounders. Multivariable Cox regression analysis also demonstrated that the operative extent was not an independent predictor of recurrence (HR 1.686, 95% CI: 0.321–8.852). Subgroup analyses further indicated that both total thyroidectomy and thyroid lobectomy resulted in comparable RFS for multifocal PTC patients with other high-risk factors, including tumor size > 1 cm (p = 0.711), lymph node metastasis (p = 0.536), and intermediate ATA risk of recurrence (p = 0.682). In conclusion, thyroid lobectomy was not associated with the risk of recurrence in patients with multifocal PTCs. Multifocality in PTC may not always require aggressive surgery.


Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 430
Author(s):  
Dirk Andreas Ridder ◽  
Lana Louisa Urbansky ◽  
Hagen Roland Witzel ◽  
Mario Schindeldecker ◽  
Arndt Weinmann ◽  
...  

Although knowledge on inflammatory signaling pathways driving cancer initiation and progression has been increasing, molecular mechanisms in hepatocarcinogenesis are still far from being completely understood. Hepatocyte-specific deletion of the MAPKKK Tak1 in mice recapitulates important steps of hepatocellular carcinoma (HCC) development, including the occurrence of cell death, steatohepatitis, dysplastic nodules, and HCCs. However, overactivation of Tak1 in mice upon deletion of its deubiquitinase Cyld also results in steatohepatitis and HCC development. To investigate Tak1 and Cyld in human HCCs, we created a tissue microarray to analyze their expression by immunohistochemistry in a large and well-characterized cohort of 871 HCCs of 561 patients. In the human liver and HCC, Tak1 is predominantly present as its isoform Tak1A and predominantly localizes to cell nuclei. Tak1 is upregulated in diethylnitrosamine-induced mouse HCCs as well as in human HCCs independent of etiology and is further induced in distant metastases. A high nuclear Tak1 expression is associated with short survival and vascular invasion. When we overexpressed Tak1A in Huh7 cells, we observed increased tumor cell migration, whereas overexpression of full-length Tak1 had no significant effect. A combined score of low Cyld and high Tak1 expression was an independent prognostic marker in a multivariate Cox regression model.


2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Yao Peng ◽  
Hui Wang ◽  
Qi Huang ◽  
Jingjing Wu ◽  
Mingjun Zhang

Abstract Background Long noncoding RNAs (lncRNAs) are important regulators of gene expression and can affect a variety of physiological processes. Recent studies have shown that immune-related lncRNAs play an important role in the tumour immune microenvironment and may have potential application value in the treatment and prognosis prediction of tumour patients. Epithelial ovarian cancer (EOC) is characterized by a high incidence and poor prognosis. However, there are few studies on immune-related lncRNAs in EOC. In this study, we focused on immune-related lncRNAs associated with survival in EOC. Methods We downloaded mRNA data for EOC patients from The Cancer Genome Atlas (TCGA) database and mRNA data for normal ovarian tissue from the Genotype-Tissue Expression (GTEx) database and identified differentially expressed genes through differential expression analysis. Immune-related lncRNAs were obtained through intersection and coexpression analysis of differential genes and immune-related genes from the Immunology Database and Analysis Portal (ImmPort). Samples in the TCGA EOC cohort were randomly divided into a training set, validation set and combination set. In the training set, Cox regression analysis and LASSO regression were performed to construct an immune-related lncRNA signature. Kaplan–Meier survival analysis, time-dependent ROC curve analysis, Cox regression analysis and principal component analysis were performed for verification in the training set, validation set and combination set. Further studies of pathways and immune cell infiltration were conducted through Gene Set Enrichment Analysis (GSEA) and the Timer data portal. Results An immune-related lncRNA signature was identified in EOC, which was composed of six immune-related lncRNAs (KRT7-AS, USP30-AS1, AC011445.1, AP005205.2, DNM3OS and AC027348.1). The signature was used to divide patients into high-risk and low-risk groups. The overall survival of the high-risk group was lower than that of the low-risk group and was verified to be robust in both the validation set and the combination set. The signature was confirmed to be an independent prognostic biomarker. Principal component analysis showed the different distribution patterns of high-risk and low-risk groups. This signature may be related to immune cell infiltration (mainly macrophages) and differential expression of immune checkpoint-related molecules (PD-1, PDL1, etc.). Conclusions We identified and established a prognostic signature of immune-related lncRNAs in EOC, which will be of great value in predicting the prognosis of clinical patients and may provide a new perspective for immunological research and individualized treatment in EOC.


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