scholarly journals Lepidic component identifies a subgroup of lung adenocarcinoma with a distinctive prognosis: a multicenter propensity-matched analysis

2020 ◽  
Vol 12 ◽  
pp. 175883592098284
Author(s):  
Erjia Zhu ◽  
Chenyang Dai ◽  
Huikang Xie ◽  
Hang Su ◽  
Xuefei Hu ◽  
...  

Background: Our aim was to investigate the prognostic impact of the lepidic component on T stage in patients with lung adenocarcinoma (LUAD). Methods: A retrospective data set including 863 cases of LUAD with lepidic component and 856 cases without lepidic component was used to identify matched lepidic-positive and lepidic-negative cohorts ( n = 376 patients per group) using a propensity-score matching. Primary outcome variables included recurrence-free survival (RFS) and overall survival (OS). Prognostic factors were assessed by Cox regression analysis and Kaplan–Meier estimates. Results: Multivariate analysis revealed that lepidic component presence was an independent prognostic factor for prolonged RFS ( p < 0.001) and OS ( p < 0.001). Furthermore, lepidic ratio (LR) >25% or ⩽25% were confirmed to be independent prolonged survival predictors. No survival differences were observed between patients with LUAD with LR >25% or ⩽25% (RFS p = 0.333; OS p = 0.078). The 5-year OS rates of patients with LUAD with a lepidic component were 90% regardless of the T stage, and these survival rates were significantly better than those of patients with LUAD without a lepidic component in the corresponding T stage. Multivariate analysis confirmed that T stage was associated with survival only in patients with LUAD without a lepidic component. Conclusions: Lepidic component presence identifies a LUAD subgroup with an excellent prognosis independent of the LR, pathological T classification. Considering the lepidic component presence may improve prognostic predictions for patients with LUAD.

Vascular ◽  
2012 ◽  
Vol 20 (4) ◽  
pp. 198-202 ◽  
Author(s):  
Bahare Fazeli ◽  
Hassan Ravari ◽  
Reza Assadi

The aim of this study was first to describe the natural history of Buerger's disease (BD) and then to discuss a clinical approach to this disease based on multivariate analysis. One hundred eight patients who corresponded with Shionoya's criteria were selected from 2000 to 2007 for this study. Major amputation was considered the ultimate adverse event. Survival analyses were performed by Kaplan–Meier curves. Independent variables including gender, duration of smoking, number of cigarettes smoked per day, minor amputation events and type of treatments, were determined by multivariate Cox regression analysis. The recorded data demonstrated that BD may present in four forms, including relapsing-remitting (75%), secondary progressive (4.6%), primary progressive (14.2%) and benign BD (6.2%). Most of the amputations occurred due to relapses within the six years after diagnosis of BD. In multivariate analysis, duration of smoking of more than 20 years had a significant relationship with further major amputation among patients with BD. Smoking cessation programs with experienced psychotherapists are strongly recommended for those areas in which Buerger's disease is common. Patients who have smoked for more than 20 years should be encouraged to quit smoking, but should also be recommended for more advanced treatment for limb salvage.


2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Jianye Tan ◽  
Haofeng Liang ◽  
Bingsheng Yang ◽  
Shuang Zhu ◽  
Guofeng Wu ◽  
...  

Osteosarcoma (OS) often occurs in children and often undergoes metastasis, resulting in lower survival rates. Information on the complexity and pathogenic mechanism of OS is limited, and thus, the development of treatments involving alternative molecular and genetic targets is hampered. We categorized transcriptome data into metastasis and nonmetastasis groups, and 400 differential RNAs (230 messenger RNAs (mRNAs) and 170 long noncoding RNAs (lncRNAs)) were obtained by the edgeR package. Prognostic genes were identified by performing univariate Cox regression analysis and the Kaplan–Meier (KM) survival analysis. We then examined the correlation between the expression level of prognostic lncRNAs and mRNAs. Furthermore, microRNAs (miRNAs) corresponding to the coexpression of lncRNA-mRNA was predicted, which was used to construct a competitive endogenous RNA (ceRNA) regulatory network. Finally, multivariate Cox proportional risk regression analysis was used to identify hub prognostic genes. Three hub prognostic genes (ABCG8, LOXL4, and PDE1B) were identified as potential prognostic biomarkers and therapeutic targets for OS. Furthermore, transcriptions factors (TFs) (DBP, ESX1, FOS, FOXI1, MEF2C, NFE2, and OTX2) and lncRNAs (RP11-357H14.16, RP11-284N8.3, and RP11-629G13.1) that were able to affect the expression levels of genes before and after transcription were found to regulate the prognostic hub genes. In addition, we identified drugs related to the prognostic hub genes, which may have potential clinical applications. Immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR) confirmed that the expression levels of ABCG8, LOXL4, and PDE1B coincided with the results of bioinformatics analysis. Moreover, the relationship between the hub prognostic gene expression and patient prognosis was also validated. Our study elucidated the roles of three novel prognostic biomarkers in the pathogenesis of OS as well as presenting a potential clinical treatment for OS.


2017 ◽  
Vol 398 (7) ◽  
pp. 765-773 ◽  
Author(s):  
Shuo Zhao ◽  
Julia Dorn ◽  
Rudolf Napieralski ◽  
Axel Walch ◽  
Sandra Diersch ◽  
...  

Abstract In serous ovarian cancer, the clinical relevance of tumor cell-expressed plasmin(ogen) (PLG) has not yet been evaluated. Due to its proteolytic activity, plasmin supports tumorigenesis, however, angiostatin(-like) fragments, derived from PLG, can also function as potent anti-tumorigenic factors. In the present study, we assessed PLG protein expression in 103 cases of advanced high-grade serous ovarian cancer (FIGO III/IV) by immunohistochemistry (IHC). In 70/103 cases, positive staining of tumor cells was observed. In univariate Cox regression analysis, PLG staining was positively associated with prolonged overall survival (OS) [hazard ratio (HR)=0.59, p=0.026] of the patients. In multivariable analysis, PLG, together with residual tumor mass, remained a statistically significant independent prognostic marker (HR=0.49, p=0.009). In another small patient cohort (n=29), we assessed mRNA expression levels of PLG by quantitative PCR. Here, elevated PLG mRNA levels were also significantly associated with prolonged OS of patients (Kaplan-Meier analysis; p=0.001). This finding was validated by in silico analysis of a microarray data set (n=398) from The Cancer Genome Atlas (Kaplan-Meier analysis; p=0.031). In summary, these data indicate that elevated PLG expression represents a favorable prognostic biomarker in advanced (FIGO III/IV) high-grade serous ovarian cancer.


2020 ◽  
Vol 27 (1) ◽  
pp. 107327482090338
Author(s):  
Fabian Haak ◽  
Isabelle Obrecht ◽  
Nadia Tosti ◽  
Benjamin Weixler ◽  
Robert Mechera ◽  
...  

Objectives: Analysis of tumor immune infiltration has been suggested to outperform tumor, node, metastasis staging in predicting clinical course of colorectal cancer (CRC). Infiltration by cells expressing OX40, a member of the tumor necrosis factor receptor family, or CD16, expressed by natural killer cells, monocytes, and dendritic cells, has been associated with favorable prognosis in patients with CRC. We hypothesized that assessment of CRC infiltration by both OX40+ and CD16+ cells might result in enhanced prognostic significance. Methods: Colorectal cancer infiltration by OX40 and CD16 expressing cells was investigated in 441 primary CRCs using tissue microarrays and specific antibodies, by immunohistochemistry. Patients’ survival was evaluated by Kaplan-Meier and log-rank tests. Multivariate Cox regression analysis, hazard ratios, and 95% confidence intervals were also used to evaluate prognostic significance of OX40+ and CD16+ cell infiltration. Results: Colorectal cancer infiltration by OX40+ and CD16+ cells was subclassified into 4 groups with high or low infiltration levels in all possible combinations. High levels of infiltration by both OX40+ and CD16+ cells were associated with lower pT stage, absence of peritumoral lymphocytic (PTL) inflammation, and a positive prognostic impact. Patients bearing tumors with high infiltration by CD16+ and OX40+ cells were also characterized by significantly longer overall survival, as compared with the other groups. These results were confirmed by analyzing an independent validation cohort. Conclusions: Combined infiltration by OX40+ and CD16+ immune cells is an independent favorable prognostic marker in CRC. The prognostic value of CD16+ immune cell infiltration is significantly improved by the combined analysis with OX40+ cell infiltration.


2020 ◽  
Vol 86 (2) ◽  
pp. 127-133
Author(s):  
Shengxiang Chen ◽  
Wenfeng Tang ◽  
Randong Yang ◽  
Xiaoxiao Hu ◽  
Zhongrong Li

Adrenal neuroblastoma (NB) is a relatively common malignancy in children. The Surveillance, Epidemiology, and End Results database was used to present demographic data and a survival analysis with the aim of making tumor management better. The Surveillance, Epidemiology, and End Results database was used to search pediatric patients (age £16 years) with NB from 2004 to 2013. The Kaplan-Meier method was used to calculate the overall survival. And, we used Cox regression analysis to determine hazard ratios for prognostic variables. Independent prognostic factors were selected into the nomogram to predict individual's three-, five-, and seven-year overall survival. The study included a total of 1870 pediatric patients with NB in our cohort. Overall, three-, five-, and seven-year survival rates for adrenal NB were 0.777, 0.701, and 0.665, respectively, whereas the rates for nonadrenal NB were 0.891, 0.859, and 0.832, respectively. The multivariate analysis identified age >1 year, no complete resection (CR)/CR, radiation, and regional/distant metastasis as independent predictors of mortality for adrenal NB. Concordance index of the nomogram was 0.665 (95% confidence interval, 0.627–0.703). Pediatric patients with adrenal NB have significantly worse survival than those with nonadrenal NB. Adrenal NB with age <1 year, treated with surgery, no radiation, and localized tumor leads to a better survival. There was no survival difference for patients to receive CR and no CR.


2020 ◽  
Author(s):  
Yang Wang ◽  
Chengping Hu

Abstract Background: Long non-coding RNAs (lncRNAs) have been reported to play essential roles in tumorigenesis and cancers prognosis, and they can be a potential cancer prognostic markers. However, in lung adenocarcinoma(LUAD), how lncRNA signatures predict the survival of patients is poorly understood. Our study aims to explore lncRNA signatures and prognostic function in LUAD.Methods: The expression and prognosis data of lncRNAs in LUAD patients was collected from the Cancer Genome Atlas (TCGA) data. All analyses were performed using the R package (version 3.6.2). Metascape, STRING and Cytoscape were used for enrichment analysis and function prediction of the lncRNA co-expressed protein-coding genes.Results: We have collected lncRNA expression data in 466 LUAD tumors, and a six-lncRNA signature(RP11-79H23.3, RP11-309M7.1, CTD-2357A8.3, RP11-108P20.4, U47924.29, LHFPL3-AS2) has been shown to be significantly related to LUAD patients’ overall survival. According to the lncRNA signatures, the high-risk and low-risk groups were divided in LUAD patients with different survival rates. Further multivariable cox regression analysis showed that the prognostic value of this signature was independent of clinical factors. The potential functional roles and hub co-expressed protein-coding genes in the six prognostic lncRNAs are shown in the functional enrichment analysis.Conclusions: These results showed that these six lncRNAs could be independent predicted prognostic biomarkers in LUAD patients.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Kai Liu ◽  
Shen Li ◽  
Bo Song ◽  
Yu Xu

Background: Increasing evidences suggest that neutrophil-to- lymphocyte ratio (NLR) is an independent predictor of poor prognosis in patients with cardiovascular disease. However, it is not clear about the relationship between NLR and prognosis in patients with cerebral venous thrombosis (CVT). Methods: Consecutive CVT patients from November 2011, through January 2017 were retrospectively identified. Unfavorable outcome was defined as modified Rankin Scale (mRS) of 3-6. Multivariate analysis and Cox regression analysis were conducted to evaluate the predictive value of NLR for unfavorable prognosis. Results: A total of 223 CVT patients were included. Multivariate analysis suggested that elevated NLR value, as a continuous variable, was significantly associated with a high risk of poor outcome (adjusted odds ratio [OR]=1.106, 95% confidence intervals [CI] 1.012-1.207, P = 0.025) and mortality (adjusted OR = 1.118; 95% CI, 1.017-1.230; P = 0.021).Receiver operating curve (ROC) analysis showed that the area under the ROC curves for NLR was 0.753 and the optimal cut-off value was 4.8 (sensitivity 81.1%, specificity 62.4%).Multivariate Cox regression analysis demonstrated that NLR>4.8 increased the risk of mortality (adjusted hazard ratio[HR]=6.111, 95% CI 1.680-22.232, P =0.006) and multivariate analysis further showed that NLR>4.8 was a significant predictor of poor functional outcome (adjusted OR=3.607, 95% CI 1.307-9.957, P =0.013). Conclusions: Elevated NLR value is associated with the long-term poor functional outcome and mortality. Future well-designed studies and experiments are needed to confirm the relationship and explore the potential mechanisms. Table 1 Results of multivariate logistic regression analysis ofpredictors for poor clinical outcome in CVTpatients. WBC,white blood cell; ANC, absolute neutrophil count; ALC, absolute lymphocyte count; *The multivariate model is adjusted for age, sex, coma, intracerebral hemorrhage, and straight sinus and/or deep CVT Figure 1. Kaplan-Meier curves of patients stratified according to the NLR value. The Kaplan-Meier curves showed a significant difference between the NLR>4.8 and NLR≤4.8 categories.


Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 619
Author(s):  
Xiuhong Li ◽  
Zian Feng ◽  
Rui Wang ◽  
Jie Hu ◽  
Xiaodong He ◽  
...  

N6-methyladenosine (m6A) RNA modification is the most abundant modification method in mRNA, and it plays an important role in the occurrence and development of many cancers. This paper mainly discusses the role of m6A RNA methylation regulators in lung adenocarcinoma (LUAD) to identify novel prognostic biomarkers. The gene expression data of 19 m6A methylation regulators in LUAD patients and its relevant clinical parameters were extracted from The Cancer Genome Atlas (TCGA) database. We selected three significantly differentially expressed m6A regulators in LUAD to construct the risk signature, and evaluated its prognostic prediction efficiency using the receiver operating characteristic (ROC) curve. Kaplan–Meier survival analysis and Cox regression analysis were used to identify the independent prognostic significance of the risk signature. The ROC curve indicated that the area under the curve (AUC) was 0.659, which means that the risk signature had a good prediction efficiency. The results of the Kaplan–Meier survival analysis and Cox regression analysis showed that the risk score can be used as an independent prognostic factor for LUAD. In addition, we explored the differential signaling pathways and cellular processes related to m6A methylation regulators in LUAD.


2021 ◽  
Author(s):  
Yue Cai ◽  
Qinglin Li ◽  
Shanshan Guo ◽  
Yanyan Chen ◽  
Fang Wang ◽  
...  

Abstract Background Patients with severe coronavirus disease 2019 (COVID-19) who develop acute kidney injury (AKI) in the intensive care unit (ICU) have extremely high rates of mortality. This study evaluated the prognostic impact of AKI duration on in-hospital mortality in elder patients.Methods We performed a retrospective study of 126 patients with confirmed COVID-19 with severe or critical disease who treated in the ICU from February 4, 2020, to April 16, 2020. AKI was defined according to the Kidney Disease Improving Global Outcomes serum creatinine (Scr) criteria. AKI patients were divided into transient AKI and persistent AKI groups based on whether Scr level returned to baseline within 48 h post-AKI.Results In total, 107 patients were included in the final analysis. The mean age was 70 (64–78) years, and 69 (64.5%) patients were men. AKI occurred in 48 (44.9%) during their ICU stay. Of these, 11 (22.9%) had transient AKI, 37 (77.9%) had persistent AKI. In-hospital mortality was 18.6% (n =11) for patients without AKI, 72.7% (n=8) for patients with transient AKI, and 86.5% (n=32) for patients with persistent AKI (P<0.001). Kaplan–Meier curve analysis revealed that patients with both transient AKI and persistent AKI had significantly higher death rates than those without AKI (log-rank P<0.001). Multivariate Cox regression analysis revealed that transient and persistent AKI were an important risk factor for in-hospital mortality in older patients with severe COVID-19 even after adjustment for variables (hazard ratio [HR]=2.582; 95% CI: 1.025–6.505; P=0.044; and HR=6.974; 95% CI: 3.334–14.588; P<0.001).Conclusions AKI duration is a useful parameter to predict of worse clinical outcomes in elder patients with COVID-19 in the ICU. Among AKI patients, those persistent AKI have a lower in-hospital survival rate than those transient AKI, emphasizing the importance of identifying an appropriate treatment window for early intervention.


Author(s):  
Junjun Sun ◽  
Yili Ping ◽  
Jingjuan Huang ◽  
Bingjie Zeng ◽  
Ping Ji ◽  
...  

Aberrant regulation of m6A mRNA modification can lead to changes in gene expression, thus contributing to tumorigenesis in several types of solid tumors. In this study, by integrating analyses of m6A methylation and mRNA expression, we identified 84 m6A-regulated mRNAs in lung adenocarcinoma (LUAD). Although the m6A methylation levels of total RNA in LUAD patient tumor tissue were reduced, the majority (75.2%) of m6A-regulated mRNAs were hypermethylated. The m6A-hypermethylated mRNAs were mainly enriched in terms related to transcription factor activity. We established a 10-m6A-regulated-mRNA signature score system through least absolute shrinkage and selection operator Cox regression analysis, with its predictive value validated by Kaplan–Meier curve and time-dependent receiver operating characteristic curves. RFXAP and KHDRBS2 from the signature also exhibited an independent prognostic value. The co-expression and interaction network analyses demonstrated the strong correlation between m6A regulators and the genes in the signature, further supporting the results of the m6A methylation modification patterns. These findings highlight the potential utility of integrating multi-omics data (m6A methylation level and mRNA expression) to accurately obtain potential prognostic biomarkers, which may provide important insights into developing novel and effective therapies for LUAD.


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