CDKN2A or CDKN2B homozygous deletion with high-immune infiltration as a favorable prognostic factor for lung adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20543-e20543
Author(s):  
Benxu Tan ◽  
Yonghong Chen ◽  
Lei Xia ◽  
Xian Yu ◽  
Yusheng Huang ◽  
...  

e20543 Background: CDKN2A and CDKN2B both acted as tumor suppressor genes by regulating the cell cycle, which in humans were located at chromosome 9, band p21.3. The frequencies of homozygous deletion (HomDel) in CDKN2A and CDKN2B in lung adenocarcinoma (LUAD) were 12.5% and 12.1%, respectively. However, the genomic, immunogenomic features and impact on the prognosis of LUAD patients with CDKN2A/B HomDel were still unclear. Methods: The cohort of this study was from The Cancer Genome Atlas (TCGA). A total of 508 LUAD patients, including 99 CDKN2A/B HomDel (homdel) and 509 CDKN2A/B wild (wild). This study explored the difference of genomic and immunogenomic landscape between homdel and wild by analysis of whole-exome sequencing (WES) and RNA sequencing data. Results: The most frequently mutated genes were TP53, TTN, MUC16, and CSMD3. Their frequencies in homdel and wild are 46% and 48%, 43% and 46%, 35% and 41%, 33% and 38%, respectively. There was no significant difference of tumor mutational burden (TMB) between homdel and wild (median TMB, 133 in homdel vs 177 in wild; Wilcoxon test, p = 0.11), and clinical characteristics including age, gender, smoking history, and tumor stage were not significantly different between homdel and wild. Homdel had a shorter overall survival (OS) than wild (Log-rank test, p = 0.04, Hazard Ratio: 0.7, 95% CI: 0.49-1.02), but there was no significant difference in progression-free survival (PFS) (Log-rank test, p = 0.05, Hazard Ratio: 0.73, 95% CI: 0.51-1.04). We used single sample gene set enrichment analysis (ssGSEA) to calculate the enrichment score (ES) of 25 immune-related pathways such as antigen presentation and T cell-mediated immunity, and then used the consensus clustering algorithm (ConsensusClusterPlus) to cluster homdel and wild respectively, and both clustered into low and high immune infiltration groups. For the high immune infiltration and low immune infiltration in homdel and wild, high immune infiltration had a longer OS (Log-rank test, p = 0.009, Hazard Ratio: 2.19, 95% CI: 1.22-3.94) and PFS (Log-rank test, p = 0.044, Hazard Ratio: 1.8, 95% CI: 1.01-3.2) than low immune infiltration in homdel. However, there was no significant heterogeneity between high and immune infiltration in terms of PFS (Log-rank test, p = 0.28, Hazard Ratio: 1.21, 95% CI: 0.87-1.68) and OS (Log-rank test, p = 0.96, Hazard Ratio: 1.01, 95% CI: 0.71-1.44) in the wild group, the wild group had longer OS than homdel group with low immune infiltration (Log-rank test, p = 0.003, Hazard Ratio: 0.5, 95% CI: 0.29-0.88), while had the same OS with homdel with high immune infiltration, irrespective of immune infiltration. And so was PFS (Log-rank test, p = 0.005, Hazard Ratio: 0.48, 95% CI: 0.27-0.82). Conclusions: CDKN2A/B homdel was an unfavorable prognostic factor for LUAD, but which with high immune infiltration might improve patient survival time.

2020 ◽  
Author(s):  
Na Li ◽  
Xiaoling Chen ◽  
Chang Liu ◽  
Yong Feng ◽  
Xiaoqiang Sun ◽  
...  

Abstract Background: The tumor microenvironment plays a vital role in tumor biology and has recently attracted widespread attention. However, the prognostic significance of integrated immune scores in lung adenocarcinoma has not yet been identified. This study aimed to systematically estimate the association between immune scores and prognosis and develop a clinical nomogram to predict the survival of patients with lung adenocarcinoma. This study also systematically explored the underlying prognostic factors of the immune score in lung adenocarcinoma.Methods: Public datasets for lung adenocarcinoma was acquired from The Cancer Genome Atlas data portal. The immune score of each sample was calculated using the ESTIMATE algorithm. Univariate and multivariate Cox regression analyses identified several significant prognostic factors and further developed a prognostic nomogram. The C-index, calibration curve, and ROC curve were used to evaluate the predictive accuracy and discriminative ability of the resultant nomogram. Results: We found that patients with higher immune scores had a better prognosis (log rank test p = 0.0004). The nomogram that integrated the immune score could effectively stratify high-risk LUAD patients in terms of clinical response. Patients in the high-risk groups usually had a worse prognosis (log rank test p < 0.0001) and higher mortality. The mortality rate in high and low risk groups was 42.67% and 26.37%, respectively (p < 0.0001). In addition, correlation analysis showed that the immune score was significantly dependent on the mRNA expression of immunotherapy-associated biomarkers (PD-1, PD-L1, and LAG3) as well as on the presence of certain immune cell subtypes, but had no correlation with tumor mutation burden.Conclusion: The immune score is a prognostic factor in lung adenocarcinoma. The nomogram with an integrated immune score can effectively predict the survival of patients with lung adenocarcinoma. The mechanism by which the immune score estimates the prognosis of patients with lung adenocarcinoma is related to the tumor immune microenvironment.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoshiya Sugiura ◽  
Rikuo Machinami ◽  
Seiichi Matsumoto ◽  
Hiroaki Kanda ◽  
Keisuke Ae ◽  
...  

AbstractIt is controversial whether patients with myxofibrosarcomas (MFSs) have better prognoses than those with undifferentiated pleomorphic sarcomas (UPSs). No useful prognostic factors have been established to date. We therefore aimed to evaluate the prognostic value of CD34 expression status in 192 patients with MFSs and UPSs. Using the log-rank test, we showed that patients with MFSs had a significantly better overall survival than did those with UPSs when defining the former as having a > 10% myxoid component (p = 0.03), but not when defining it as having a > 50% myxoid component (p = 0.1). Under the definition of MFSs as > 10% myxoid component, the log-rank test revealed that the diagnosis of the UPS and the CD34 loss (p < 0.001) were significant adverse predictors of overall survival. As per the Cox model, the CD34 loss remained an independent prognostic factor (hazard ratio = 3.327; 95% confidence interval 1.334–8.295), while the diagnosis of the UPS was a nonsignificant confounding factor (hazard ratio = 1.084; 95% confidence interval 0.679–1.727). In conclusion, CD34 expression status is a useful prognostic factor in patients with MFS and UPS, and it should be incorporated into grading systems that are used to predict outcomes.


2021 ◽  
Author(s):  
Xilin Shen ◽  
Hongru Shen ◽  
Mengyao Feng ◽  
Dan Wu ◽  
Yichen Yang ◽  
...  

Abstract Background Brain tumor ranks the most devastating cancer type. The complex tumor immune microenvironment prevents brain tumor from therapeutic benefits. The purpose of this study was to stratify brain tumors based on their distinct immune infiltration signatures to facilitate better clinical decision making and prognosis prediction.Methods We developed a deep learning model to characterize immune infiltration from transcriptome. The developed model was applied to distill expression signatures of transcriptome of brain tumor samples. We performed molecular subtyping with the extracted expression signatures to unveil brain tumor subtypes. Computational methods including gene set enrichment analysis, Kaplan-Meier survival and multivariate Cox regression analyses were employed.Results We identified two distinctive subtypes (i.e. C1/2) of brain tumor featured by distinct immune infiltration signatures. The C1 subtype is characterized by protective immune infiltration signatures, including high infiltration of CD8+ T cells and activation of CX3CL1. The C2 subtype has an extensive infiltration of tumor-associated macrophages and microglia, and was enriched with immune suppressive, wound healing and angiogenic signatures. The C1 subtype had significantly better prognosis as compared with C2 (Log-rank test, HR: 2.5, 95% CI: 2.2 – 2.7; P = 8.2e-78). This difference remained statistically significant (multivariate Cox model, HR: 2.2, 95% CI: 1.7 – 2.9; P = 3.7e-10) by taking into account age, gender, recurrent/secondary status at sampling time, tumor grade, histology, radio-chemotherapy, IDH mutation, MGMT methylation and co-deletion of 1p and 19q. This finding was validated in 6 datasets. The C2 subtype of glioblastoma patients with IDH mutation has poor survival analogous to those without IDH mutation (Log-rank test, adjusted P = 0.8), while C1 has favorable prognosis as compared with glioblastoma of C2 subtype with IDH mutation (Log-rank test, adjusted P = 1.2e-3) or without IDH mutation (Log-rank test, adjusted P = 1.3e-6).Conclusions We identified two distinctive subtypes of brain tumor with different immune infiltration signatures and prognosis. Our finding is helpful for better understanding of brain tumor and has potential clinical utilities.


2021 ◽  
Vol 11 ◽  
Author(s):  
Xilin Shen ◽  
Xiaoli Wang ◽  
Hongru Shen ◽  
Mengyao Feng ◽  
Dan Wu ◽  
...  

BackgroundBrain tumor ranks as the most devastating cancer type. The complex tumor immune microenvironment prevents brain tumor from receiving therapeutic benefits. The purpose of this study was to stratify brain tumors based on their distinct immune infiltration signatures to facilitate better clinical decision making and prognosis prediction.MethodsWe developed a deep learning model to characterize immune infiltration from transcriptome. The developed model was applied to distill expression signatures of transcriptome of brain tumor samples. We performed molecular subtyping with the extracted expression signatures to unveil brain tumor subtypes. Computational methods, including gene set enrichment analysis, Kaplan-Meier survival and multivariate Cox regression analyses, were employed.ResultsWe identified two distinctive subtypes (i.e. C1/2) of brain tumor featured by distinct immune infiltration signatures. The C1 subtype is characterized by protective immune infiltration signatures, including high infiltration of CD8+ T cells and activation of CX3CL1. The C2 subtype has an extensive infiltration of tumor-associated macrophages and microglia, and was enriched with immune suppressive, wound-healing, and angiogenic signatures. The C1 subtype had significantly better prognosis as compared with C2 (Log-rank test, HR: 2.5, 95% CI: 2.2 – 2.7; P = 8.2e-78). This difference remained statistically significant (multivariate Cox model, HR: 2.2, 95% CI: 1.7 – 2.9; P = 3.7e-10) by taking into account age, gender, recurrent/secondary status at sampling time, tumor grade, histology, radio-chemotherapy, IDH mutation, MGMT methylation, and co-deletion of 1p and 19q. This finding was validated in six datasets. The C2 subtype of glioblastoma patients with IDH mutation has poor survival analogous to those without IDH mutation (Log-rank test, adjusted P = 0.8), while C1 has favorable prognosis as compared with glioblastoma of C2 subtype with IDH mutation (Log-rank test, adjusted P = 1.2e-3) or without IDH mutation (Log-rank test, adjusted P = 1.3e-6).ConclusionsWe identified two distinctive subtypes of brain tumor with different immune infiltration signatures, which might be helpful as an independent prognosticator for brain tumor.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Teppei Okamoto ◽  
Daisuke Noro ◽  
Shingo Hatakeyama ◽  
Shintaro Narita ◽  
Koji Mitsuzuka ◽  
...  

Abstract Background Anemia has been a known prognostic factor in metastatic hormone-sensitive prostate cancer (mHSPC). We therefore examined the effect of anemia on the efficacy of upfront abiraterone acetate (ABI) in patients with mHSPC. Methods We retrospectively evaluated 66 mHSPC patients with high tumor burden who received upfront ABI between 2018 and 2020 (upfront ABI group). We divided these patients into two groups: the anemia-ABI group (hemoglobin < 13.0 g/dL, n = 20) and the non-anemia-ABI group (n = 46). The primary objective was to examine the impact of anemia on the progression-free survival (PFS; clinical progression or PC death before development of castration resistant PC) of patients in the upfront ABI group. Secondary objectives included an evaluation of the prognostic significance of upfront ABI and a comparison with a historical cohort (131 mHSPC patients with high tumor burden who received androgen deprivation therapy (ADT/complete androgen blockade [CAB] group) between 2014 and 2019). Results We found that the anemia-ABI group had a significantly shorter PFS than the non-anemia-ABI group. A multivariate Cox regression analysis showed that anemia was an independent prognostic factor of PFS in the upfront ABI group (hazard ratio, 4.66; P = 0.014). Patients in the non-anemia-ABI group were determined to have a significantly longer PFS than those in the non-anemia-ADT/CAB group (n = 68) (P < 0.001). However, no significant difference was observed in the PFS between patients in the anemia-ABI and the anemia-ADT/CAB groups (n = 63). Multivariate analyses showed that upfront ABI could significantly prolong the PFS of patients without anemia (hazard ratio, 0.17; P < 0.001), whereas ABI did not prolong the PFS of patients with anemia. Conclusion Pretreatment anemia was a prognostic factor among mHSPC patients who received upfront ABI. Although the upfront ABI significantly improved the PFS of mHSPC patients without anemia, its efficacy in patients with anemia might be limited.


2012 ◽  
Vol 23 (4) ◽  
pp. 399-402 ◽  
Author(s):  
Fábio Lourenço Romano ◽  
Rodrigo Alexandre Valério ◽  
Jaciara Miranda Gomes-Silva ◽  
José Tarcísio Lima Ferreira ◽  
Gisele Faria ◽  
...  

The purpose of the present study was to evaluate in vivo the failure rate of metallic brackets bonded with two orthodontic composites. Nineteen patients with ages ranging from 10.5 to 38.7 years needing corrective orthodontic treatment were selected for study. The enamel surfaces from second premolars to second premolars were treated with Transbond Plus-Self Etching Primer (3M Unitek). Next, 380 orthodontic brackets were bonded on maxillary and mandibular teeth, as follows: 190 with Transbond XT composite (3M Unitek) (control) and 190 with Transbond Plus Color Change (3M Unitek) (experimental) in contralateral quadrants. The bonded brackets were light cured for 40 s, and initial alignment archwires were inserted. Bond failure rates were recorded over a six-month period. At the end of the evaluation, six bond failures occurred, three for each composite. Kaplan-Meyer method and log-rank test (Mantel-Cox) was used for statistical analysis, and no statistically significant difference was found between the materials (p=0.999). Both Transbond XT and Transbond Plus Color Change composites had low debonding rates over the study period.


2014 ◽  
Vol 13 (2) ◽  
pp. 140-144 ◽  
Author(s):  
Jordan D. Lane ◽  
John Mugamba ◽  
Peter Ssenyonga ◽  
Benjamin C. Warf

Object Antibiotic-impregnated shunts have yet to find widespread use in the developing world, largely due to cost. Given potential differences in the microbial spectrum, their effectiveness in preventing shunt infection for populations in low-income countries may differ and has not been demonstrated. This study is the first to compare the efficacy of a Bactiseal shunt system with a non–antibiotic-impregnated system in a developing country. Methods The Bactiseal Universal Shunt (BUS) was placed in 80 consecutive Ugandan children who required a shunt. In this retrospective cohort study, the outcome for that group was compared with the outcome for the immediately preceding 80 consecutive children in whom a Chhabra shunt had been placed. The primary end points were shunt failure, shunt infection, and death. Shunt survival was analyzed using the Kaplan-Meier method. Significance of differences between groups was tested using the log-rank test, chi-square analysis, Fisher's exact test, and t-test. Results There was no difference between groups in regard to age, sex, or etiology of hydrocephalus. Mean follow-up for cases of nonfailure was 7.6 months (median 7.8 months, interquartile range 6.5–9.5 months). There was no significant difference between groups for any end point. The BUS group had fewer infections (4 vs 11), but the difference was not significant (p = 0.086, log-rank test). Gram-positive cocci were the most common culturable pathogens in the Chhabra group, while the only positive culture in the BUS group was a gram-negative rod. Conclusions These results provide equipoise for a randomized controlled trial in the same population and this has been initiated. It is possible that the observed trends may become significant in a larger study. The more complex task will involve determining not only the efficacy, but also the cost-effectiveness of using antibiotic-impregnated shunt components in limited-resource settings.


2021 ◽  
Vol 18 (6) ◽  
pp. 9336-9356
Author(s):  
Sidan Long ◽  
◽  
Shuangshuang Ji ◽  
Kunmin Xiao ◽  
Peng Xue ◽  
...  

<abstract> <sec><title>Background</title><p>LTB4 receptor 1 (LTB4R), as the high affinity leukotriene B4 receptor, is rapidly revealing its function in malignancies. However, it is still uncertain.</p> </sec> <sec><title>Methods</title><p>We investigated the expression pattern and prognostic significance of LTB4R in pan-cancer across different databases, including ONCOMINE, PrognoScan, GEPIA, and Kaplan-Meier Plotter, in this study. Meanwhile, we explored the significance of LTB4R in tumor metastasis by HCMDB. Then functional enrichment analysis of related genes was performed using GeneMANIA and DAVID. Lastly, utilizing the TIMER datasets, we looked into the links between LTB4R expression and immune infiltration in malignancies.</p> </sec> <sec><title>Results</title><p>In general, tumor tissue displayed higher levels of LTB4R expression than normal tissue. Although LTB4R had a negative influence on pan-cancer, a high expression level of LTB4R was protective of LIHC (liver hepatocellular carcinoma) patients' survival. There was no significant difference in the distribution of LTB4R between non-metastatic and metastatic tumors. Based on Gene Set Enrichment Analysis, LTB4R was implicated in pathways involved in inflammation, immunity, metabolism, and cancer diseases. The correlation between immune cells and LTB4R was found to be distinct across cancer types. Furthermore, markers of infiltrating immune cells, such as Treg, T cell exhaustion and T helper cells, exhibited different LTB4R-related immune infiltration patterns.</p> </sec> <sec><title>Conclusion</title><p>The LTB4R is associated with immune infiltrates and can be used as a prognostic biomarker in pan-cancer.</p> </sec> </abstract>


2021 ◽  
Vol 12 ◽  
Author(s):  
Guomin Wu ◽  
Qihao Wang ◽  
Ting Zhu ◽  
Linhai Fu ◽  
Zhupeng Li ◽  
...  

This study aimed to establish a prognostic risk model for lung adenocarcinoma (LUAD). We firstly divided 535 LUAD samples in TCGA-LUAD into high-, medium-, and low-immune infiltration groups by consensus clustering analysis according to immunological competence assessment by single-sample gene set enrichment analysis (ssGSEA). Profile of long non-coding RNAs (lncRNAs) in normal samples and LUAD samples in TCGA was used for a differential expression analysis in the high- and low-immune infiltration groups. A total of 1,570 immune-related differential lncRNAs in LUAD were obtained by intersecting the above results. Afterward, univariate COX regression analysis and multivariate stepwise COX regression analysis were conducted to screen prognosis-related lncRNAs, and an eight-immune-related-lncRNA prognostic signature was finally acquired (AL365181.2, AC012213.4, DRAIC, MRGPRG-AS1, AP002478.1, AC092168.2, FAM30A, and LINC02412). Kaplan–Meier analysis and ROC analysis indicated that the eight-lncRNA-based model was accurate to predict the prognosis of LUAD patients. Simultaneously, univariate COX regression analysis and multivariate COX regression analysis were undertaken on clinical features and risk scores. It was illustrated that the risk score was a prognostic factor independent from clinical features. Moreover, immune data of LUAD in the TIMER database were analyzed. The eight-immune-related-lncRNA prognostic signature was related to the infiltration of B cells, CD4+ T cells, and dendritic cells. GSEA enrichment analysis revealed significant differences in high- and low-risk groups in pathways like pentose phosphate pathway, ubiquitin mediated proteolysis, and P53 signaling pathway. This study helps to treat LUAD patients and explore molecules related to LUAD immune infiltration to deeply understand the specific mechanism.


2010 ◽  
Vol 28 (4) ◽  
pp. E5 ◽  
Author(s):  
Isaac Yang ◽  
Michael E. Sughrue ◽  
Martin J. Rutkowski ◽  
Rajwant Kaur ◽  
Michael E. Ivan ◽  
...  

Object Craniopharyngiomas have a propensity to recur after resection, potentially causing death through their aggressive local behavior in their critical site of origin. Recent data suggest that subtotal resection (STR) followed by adjuvant radiotherapy (XRT) may be an appealing substitute for gross-total resection (GTR), providing similar rates of tumor control without the morbidity associated with aggressive resection. Here, the authors summarize the published literature regarding rates of tumor control with various treatment modalities for craniopharyngiomas. Methods The authors performed a comprehensive search of the English language literature to identify studies publishing outcome data on patients undergoing surgery for craniopharyngioma. Rates of progression-free survival (PFS) and overall survival (OS) were determined through Kaplan-Meier analysis. Results There were 442 patients who underwent tumor resection. Among these patients, GTR was achieved in 256 cases (58%), STR in 101 cases (23%), and STR+XRT in 85 cases (19%). The 2- and 5-year PFS rates for the GTR group versus the STR+XRT group were 88 versus 91%, and 67 versus 69%, respectively. The 5- and 10-year OS rates for the GTR group versus the STR+XRT group were 98 versus 99%, and 98 versus 95%, respectively. There was no significant difference in PFS (log-rank test) or OS with GTR (log-rank test). Conclusions Given the relative rarity of craniopharyngioma, this study provides estimates of outcome for a variety of treatment combinations, as not all treatments are an option for all patients with these tumors.


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