scholarly journals In-Silico Multi-Omics Analysis of the Functional Significance of Calmodulin 1 in Multiple Cancers

2022 ◽  
Vol 12 ◽  
Author(s):  
Maolin Yao ◽  
Lanyi Fu ◽  
Xuedong Liu ◽  
Dong Zheng

Aberrant activation of calmodulin 1 (CALM1) has been reported in human cancers. However, comprehensive understanding of the role of CALM1 in most cancer types has remained unclear. We systematically analyzed the expression landscape, DNA methylation, gene alteration, immune infiltration, clinical relevance, and molecular pathway of CALM1 in multiple cancers using various online tools, including The Cancer Genome Atlas, cBioPortal and the Human Protein Atlas databases. Kaplan–Meier and receiver operating characteristic (ROC) curves were plotted to explore the prognostic and diagnostic potential of CALM1 expression. Multivariate analyses were used to evaluate whether the CALM1 expression could be an independent risk factor. A nomogram predicting the overall survival (OS) of patients was developed, evaluated, and compared with the traditional Tumor-Node-Metastasis (TNM) model using decision curve analysis. R language was employed as the main tool for analysis and visualization. Results revealed CALM1 to be highly expressed in most cancers, its expression being regulated by DNA methylation in multiple cancers. CALM1 had a low mutation frequency (within 3%) and was associated with immune infiltration. We observed a substantial positive correlation between CALM1 expression and macrophage and neutrophil infiltration levels in multiple cancers. Different mutational forms of CALM1 hampered immune cell infiltration. Additionally, CALM1 expression had high diagnostic and prognostic potential. Multivariate analyses revealed CALM1 expression to be an independent risk factor for OS. Therefore, our newly developed nomogram had a higher clinical value than the TNM model. The concordance index, calibration curve, and time-dependent ROC curves of the nomogram exhibited excellent performance in terms of predicting the survival rate of patients. Moreover, elevated CALM1 expression contributes to the activation of cancer-related pathways, such as the WNT and MAPK pathways. Overall, our findings improved our understanding of the function of CALM1 in human cancers.

2016 ◽  
Vol 65 (07) ◽  
pp. 528-534 ◽  
Author(s):  
Yuping Li ◽  
Gening Jiang ◽  
Chang Chen ◽  
Xuefei Hu

Objectives Whether pneumonectomy is needed for the treatment of destroyed lungs is still controversial and unresolved in the clinic. Pneumonectomy is destructive and is associated with a significant incidence of postoperative complications. The purpose of this study is to analyze the operative techniques, postoperative morbidity, mortality, and long-term outcomes of patients with destroyed lungs who underwent pneumonectomy. Patients and Methods We retrospectively analyzed 137 patients with destroyed lungs who underwent pneumonectomy. The data were queried for the details of operative technique, development of perioperative complications, mortality, and long-term survival. Univariate and multivariate analyses were performed to investigate the risk factors of pneumonectomy among the patients. Results A total of 77 male and 60 female patients were reviewed. The youngest patient was 18 years, and the oldest was 75 years, with a mean age of 40.1 years. Postoperative complications were observed in 25 patients (18.2%). The rate of bronchopleural fistula (BPF) was 5.1% (7/137). Two perioperative deaths (1.5%) were noted. Univariate and multivariate analyses indicated the blood loss (hazard ratio [HR], 5.32; 95% confidence interval [CI], 1.27–18.50; p = 0.021) was the independent risk factor of postoperative complications, and the type of the disease (HR, 4.50; 95% CI, 1.19–9.69; p = 0.034) was the independent risk factor of the BPF, for the patients with destroyed lung after pneumonectomy. Conclusion Pneumonectomy for destroyed lung is a high risk for postoperative complications. Our findings suggested that pneumonectomy in destroyed lung was satisfactory with strict surgical indications, adequate preoperative preparation, and careful operative technique, and the long-term outcomes can be especially satisfactory. Pneumonectomy for destroyed lung is still a treatment option.


2019 ◽  
Vol 8 (8) ◽  
pp. 1115 ◽  
Author(s):  
Hsu Wu ◽  
Jhe-Cyuan Guo ◽  
Shih-Hung Yang ◽  
Yu-Wen Tien ◽  
Sung-Hsin Kuo

Background: Pancreatic cancer is a catastrophic disease with high recurrence and death rates, even in early stages. Early detection and early treatment improve survival in many cancer types but have not yet been clearly documented to do so in pancreatic cancer. In this study, we assessed the benefit on survival resulting from different patterns of surveillance in daily practice after curative surgery of early pancreatic cancer. Methods: Patients with pancreatic ductal adenocarcinoma who had received curative surgery between January 2000 and December 2013 at our institute were retrospectively reviewed. Patients were classified into one of four groups, based on surveillance strategy: the symptom group, the imaging group, the marker group (carbohydrate antigen 19-9 and/or carcinoembryonic antigen), and the intense group (both imaging and tumor marker assessment). Overall survival (OS), relapse-free survival (RFS), and post-recurrence overall survival (PROS) were evaluated. Results: One hundred and eighty-one patients with documented recurrence or metastasis were included in our analysis. The median OS for patients in the symptom group, imaging group, marker group, and intense group were 21.4 months, 13.9 months, 20.5 months, and 16.5 months, respectively (p = 0.670). Surveillance with imaging, tumor markers, or both was not an independent risk factor for OS in univariate and multivariate analyses. There was no significant difference in median RFS (symptom group, 11.7 months; imaging group, 6.3 months; marker group, 9.3 months; intense group, 6.9 months; p = 0.259) or median PROS (symptom group, 6.9 months; imaging group, 7.5 months; marker group, 5.0 months; intense group, 7.8 months; p = 0.953) between the four groups. Multivariate analyses identified poor Eastern Cooperative Oncology Group Performance Status (ECOG PS) (≥1), primary tumor site (tail), and tumor grade (poor differentiation) were poor prognostic factors for OS. Conclusions: Surveillance with regular imaging, tumor marker, or both was not an independent risk factor for OS of pancreatic cancer patients who undergo curative tumor resection.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 707-707
Author(s):  
Maria E Figueroa ◽  
Sanne Lugthart ◽  
Yushan Li ◽  
Claudia Erpelinck-Verschueren ◽  
Xutao Deng ◽  
...  

Abstract Abstract 707 Epigenetic deregulation of genes through aberrant DNA methylation has been widely reported in cancer. We hypothesized that in AML this aberrant DNA methylation does not occur randomly, but rather occurs in specific and distinct patterns. Therefore, large-scale genome-wide analysis of the DNA methylome could help explain and define the complexity underlying leukemia biology and reveal the existence of epigenetically defined variants of AML. Using the HELP microarray assay, which measures DNA methylation at 50,000 CpG sites annotated to ∼14,000 promoters, we obtained DNA methylation profiles for 344 AML patients seen at Erasmus University Medical Center. Median follow-up based on survivors was 18.2 months (7-215); median age: 48 years (15-77). Unsupervised analysis (hierarchical clustering, correlation distance with Ward's clustering method) demonstrated that based on their methylation profiles AML patients distributed into 16 cohorts. 11 of these groups were also defined by the presence of specific molecular lesions: inv(16) [cluster 1], t(8;21) [cluster 3], t(15;17) [cluster 6], CEBPA-mutant [clusters 4 and 9], CEBPA-silenced [cluster 10] NPM1-mutant [clusters 12, 13, 14 and 16] and 11q23 abnormalities [cluster 11]. Enrichment for cases harboring a specific molecular lesion within a given cluster was determined using Fisher's exact test (p<0.01). Additionally, 5 new AML subtypes were defined based on epigenetic profiling alone and had no other clinical or molecular feature in common. Kaplan-Meier survival analysis revealed a significant difference in overall survival (OS) between these novel AML subtypes: 2-year OS±SE; 58.8%±8.4% and 45.2%±8.9% for clusters 5 and 7, respectively, vs. 23.6%±5.7%, 26.4%±9.2% and 33.3%±13.6%, for clusters 2, 8 and 15, respectively (log rank test, p=0.04). After adjustment for age, cytogenetic risk, NPM1 and FLT3-ITD status in a multivariate Cox proportional hazards regression model including all the clusters with ≥ 10 patients, 4 of these 5 novel clusters presented a statistically significant increased hazard ratio compared to the favorable risk inv(16) cluster. In contrast, the clinical outcomes of patients in cluster 5 were not significantly different from favorable risk patients with inv(16). In order to identify the genes affected by aberrant DNA methylation for each cluster, we performed a supervised analysis comparing each of the 16 clusters to normal CD34+ bone marrow progenitors (n=8) using ANOVA followed by Dunnet post hoc test, and selected genes with adjusted p values <0.05 and a methylation change >30%. The DNA methylation signatures of each cluster featured involvement of distinct gene networks and DNA regulatory elements, and displayed distinct degrees of hyper or hypomethylation with respect to normal CD34+ bone marrow cells. Of note, in spite of the variation in methylation across the 16 clusters, we identified a set of 45 genes that were almost universally aberrantly methylated (in >70% cases and present in at least 10/16 cluster signatures). This common epigenetic signature included the tumor suppressor PDZD2, the nuclear import proteins IPO8 and TNPO3, PIAS2, a regulator of MAP kinase signaling, CDK8, and CSDA, a regulator of CSF2. Gene expression profiling of the same patients indicated that at least 50% of these genes were also aberrantly silenced compared to normal CD34+ cells. Finally, we randomly divided the 344-patient cohort into a training group of 200 patients, a test group (n=95) and an independent validation group (n=49), and using the Supervised Principal Components algorithm identified a 15-gene methylation classifier that was predictive of OS (p<0.009) and event free survival (p<0.013). Furthermore, after adjustment for age, cytogenetic risk, NPM1, FLT3 and CEBPA status in a multivariate analysis, this classifier remained an independent risk factor for OS (Hazard ratio 1.29, 95% CI: 1.11-1.49; p<0.001). In summary, we have i) demonstrated that unique and distinct DNA methylation patterns characterize distinct forms of AML; ii) identified novel, epigenetically defined subgroups of AML with distinct clinical behavior; iii) revealed the presence of a consistently aberrantly methylated signature across AML subtypes, with confirmed silencing of the genes involved; and iv) report a 15-gene methylation classifier predictive of OS, and confirmed as an independent risk factor when adjusted for known AML covariates. Disclosures: No relevant conflicts of interest to declare.


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 418-418
Author(s):  
Shozo Yokoyama ◽  
Junji Ieda ◽  
Naoyuki Yamamoto ◽  
Yasuyuki Mitani ◽  
Yuki Mizumoto ◽  
...  

418 Background: Hollow spheroid (HS) is a morophogenesis after budding at invasion front of colorectal cancer (CRC) tissue. HS formation of CRC cells has been shown to be induced by Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 (CEACAM1) long cytoplasmic isoform dominance condition in three-dimensional (3D) in vitro culture. The aim of the current study is to address the existence and the clinical implication of HS in colorectal cancer. Methods: Immunohistochemical analyses were conducted with CEACAM1, CEACAM1-L, to address the existence of CEACAM1 expressing HS beyond the invasion front of CRC. The risk factors for metastases and survival were calculated using univariate and multivariate analyses on clinical samples from 164 patients with CRC. To investigate the role of HS for chemoresistance to 5-fluorouracil (5-FU), the risk factors for recurrence after adjuvant chemotherapy were calculated using univariate and multivariate analyses on clinical samples from 82 patients with Stage III CRC. Results: Immunohistochemical analyses showed that CEACAM1 expressing HS existed at the invasion front of colorectal cancer tissues. A multivariate analysis showed that the HS is an independent risk factor for lymph node metastasis (p = 0.004) and distant metastasis (p = 0.002). HS was also identified to be an independent prognostic factor by a Cox proportional hazards model (p = 0.020). The Kaplan-Meier evaluation for the overall survival analysis showed that HS was significantly associated with a shorter survival (p < 0.0001). Moreover, a multivariate analysis for recurrence after adjuvant chemotherapy showed that the HS is an independent risk factor (p = 0.0079). These results suggested that HS indicates malignant and chemoresistant phenotype. Conclusions: HS was significantly correlated with CRC metastasis, poor survival and chemoresistance to 5-FU. HS beyond the invasion front of CRC can be useful for diagnosis of malignant potential, and may be novel therapeutic target.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yu Yan ◽  
Lina Qiao ◽  
Yimin Hua ◽  
Shuran Shao ◽  
Nanjun Zhang ◽  
...  

Abstract Background Intravenous immunoglobulin (IVIG) resistance prediction is one of the primary clinical issues and study hotspots in KD. This study aimed to prospectively investigate the value of albumin-bilirubin grade (ALBI) in predicting IVIG resistance in KD and to assess whether ALBI has more predictive value or accuracy than either ALB or TBil alone in predicting IVIG resistance. Methods A total of 823 patients with KD were prospectively enrolled. The clinical and laboratory data were compared between the IVIG-response group (n = 708) and the IVIG-resistance group (n = 115). Multivariate logistic regression analysis was performed to identify the independent risk factors for IVIG resistance. Receiver operating characteristic (ROC) curves analysis was applied to assess the validity of ALBI, ALB, and TBil in predicting IVIG resistance. Results ALBI was significantly higher in patients with IVIG resistance and was identified as an independent risk factor for IVIG resistance in KD. The parameter of ALBI ≥ − 2.57 (AUC: 0.705, 95 %CI: 0.672–0.736), ALB ≤ 33.0 g/L (AUC: 0.659, 95 %CI: 0.626–0.692), and TBil ≥ 16.0µmol/L (AUC: 0.626, 95 %CI: 0.592–0.659), produced a sensitivity, specificity, PPV, and NPV of 0.617, 0.657, 0.226 and 0.914; 0.374, 0.850, 0.289 and 0.893; 0.269, 0.941, 0.425 and 0.888, respectively. Conclusions A higher ALBI was an independent risk factor for IVIG resistance in KD. It yielded better predictive ability than ALB and TBil alone for initial IVIG resistance.


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