scholarly journals Bioinformatics analysis for the role of CALR in human cancers

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261254
Author(s):  
Yijun Li ◽  
Xiaoxu Liu ◽  
Heyan Chen ◽  
Peiling Xie ◽  
Rulan Ma ◽  
...  

Cancer is one of the most important public health problems in the world. The curative effect of traditional surgery, radiotherapy and chemotherapy is limited and has inevitable side effects. As a potential target for tumor therapy, few studies have comprehensively analyzed the role of CALR in cancers. Therefore, by using GeneCards, UALCAN, GEPIA, Kaplan-Meier Plotter, COSMIC, Regulome Explorer, String, GeneMANIA and TIMER databases, we collected and analyzed relevant data to conduct in-depth bioinformatics research on the CALR expression in Pan-cancer to assess the possibility of CALR as a potential therapeutic target and survival biomarker. We studied the CALR expression in normal human tissues and various tumors of different stages, and found that CALR expression was associated with relapse free survival (RFS). We verified the expression of CALR in breast cancer cell lines by vitro experiments. Mutations of CALR were widely present in tumors. CALR interacted with different genes and various proteins. In tumors, a variety of immune cells are closely related to CALR. In conclusion, CALR can be used as a biomarker for predicting prognosis and a potential target for tumor molecular and immunotherapy.

2020 ◽  
pp. 1-15
Author(s):  
Heyan Chen ◽  
Kunlong Li ◽  
Yijun Li ◽  
Peilin Xie ◽  
Jianjun He ◽  
...  

BACKGROUND: Cancer will become the leading cause of death worldwide in the 21st century, meanwhile, immunotherapy is the most popular cancer treatment methods in recent years. COPI Coat Complex Subunit Beta 1 (COPB1) relates to human innate immunity. However, the role of COPB1 in pan-cancer remains unclear. OBJECTIVE: The purpose of this study was to explore the relationship between COPB1 mRNA expression and tumor infiltrating lymphocytes and immune examination sites in pan-cancer. METHODS: Data from multiple online databases were collected. The BioGPS, UALCAN Database, COSMIC, cBioPortal, Cancer Regulome tools, Kaplan-Meier Plotter and TIMER website were utilized to perform the analysis. RESULTS: Upregulation of COPB1 has been widely observed in tumors tissues compared with normal tissues. Although COPB1 has poor prognosis in pan-cancer, COPB1 high expression was beneficial to the survival of ESCA patients. Unlike ESCA, COPB1 expression in STAD was positively correlated with tumor infiltrating lymphocytes, including B cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells. Finally, we also found that the expression of COPB1 in STAD was positively correlated with PD-L1 and CTLA4. CONCLUSIONS: COPB1 may be a prognostic biomarker for pan-carcinoma, and also provide an immune anti-tumor strategy for STAD based on the expression of COPB1.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yanpeng Ding ◽  
Nuomin Liu ◽  
Mengge Chen ◽  
Yulian Xu ◽  
Sha Fang ◽  
...  

Abstract Background BLCA is a common cancer worldwide, and it is both aggressive and fatal. Immunotherapy (ICT) has achieved an excellent curative effect in BLCA; however, only some BLCA patients can benefit from ICT. MT1L is a pseudogene, and a previous study suggested that MT1L can be used as an indicator of prognosis in colorectal cancer. However, the role of MT1L in BLCA has not yet been determined. Methods Data were collected from TCGA, and logistic regression, Kaplan-Meier plotter, and multivariate Cox analysis were performed to demonstrate the correlation between the pseudogene MT1L and the prognosis of BLCA. To identify the association of MT1L with tumor-infiltrating immune cells, TIMER and TISIDB were utilized. Additionally, GSEA was performed to elucidate the potential biological function. Results The expression of MT1L was decreased in BLCA. Additionally, MT1L was positively correlated with immune cells, such as Tregs (ρ = 0.708) and MDSCs (ρ = 0.664). We also confirmed that MT1L is related to typical markers of immune cells, such as PD-1 and CTLA-4. In addition, a high MT1L expression level was associated with the advanced T and N and high grade in BLCA. Increased expression of MT1L was significantly associated with shorter OS times of BLCA patients (p < 0.05). Multivariate Cox analysis revealed that MT1L expression could be an independent prognostic factor in BLCA. Conclusion Collectively, our findings demonstrated that the pseudogene MT1L regulates the immune microenvironment, correlates with poor survival, and is an independent prognostic biomarker in BLCA.


2020 ◽  
Author(s):  
Fei Luo ◽  
Jiaxi Han ◽  
Yatong Chen ◽  
Kuo Yang ◽  
Zhihua Zhang ◽  
...  

Aims: To determine the role of lamin B1 (LMNB1) in the progression and metastasis of primary prostate cancer (PC). Patients & methods: Two PC cohorts were used to investigate the clinical relationship between LMNB1 expression and tumor progression and metastasis. Results: The qRT-PCR results revealed that LMNB1 expression was markedly increased in patients with aggressive features and was associated with worse prognosis. Logistic regression analyses indicated that LMNB1 expression is an independent risk factor for distant metastasis. Kaplan–Meier analysis showed that increased LMNB1 levels were related to poor disease-free survival in the primary PC cohort. Conclusion: This study reveals that upregulation of LMNB1 is associated with cancer metastasis and poor survival outcomes in primary PC patients.


2021 ◽  
Vol 11 ◽  
Author(s):  
Min Wu ◽  
Pan Zhang ◽  
Penghui Wang ◽  
Zhen Fang ◽  
Yaqin Zhu

ObjectiveThis study aims to identify the potential value of flap endonuclease 1 (FEN1) as a diagnostic and prognostic marker for breast cancer (BC).MethodsELISA was used to measure serum FEN1 levels and ECLIA for CA153 and CEA levels. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value. Oncomine and UALCAN databases were used to analyze the differences in FEN1 mRNA and protein expressions. Kaplan-Meier Plotter database was then used to assess the prognostic value.ResultsBioinformatics analysis showed that the FEN1 mRNA and protein levels were significantly higher in BC tissues than in normal tissues. FEN1 was detected in culture medium of BC cell lines and serum FEN1 concentrations were significantly increased in BC patients than in cancer-free individuals. Besides, FEN1 exhibited higher diagnostic accuracy (AUC values&gt;0.800) than CA153 and CEA for distinguishing BC patients, especially early BC, from the healthy and benign groups, or individually. Additionally, serum FEN1 levels were significantly associated with the stage (P=0.001) and lymph invasion (P=0.016), and serum FEN1 levels were increased with the development of BC. Furthermore, serum FEN1 levels were significantly decreased in post-operative patients than in pre-operative patients (P=0.016). Based on the Kaplan-Meier Plotter database, the survival analysis indicated that FEN1 overexpression was associated with poor prognoses for overall survival (OS), relapse-free survival (RFS), and distant metastasis-free survival (DMFS) in BC patients.ConclusionFEN1 might be a novel diagnostic and prognostic marker for BC.


2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Xinyu Liu ◽  
Ying Liu ◽  
Qiangshan Wang ◽  
Siqi Song ◽  
Lingjun Feng ◽  
...  

The minichromosome maintenance (MCM) protein family plays a key role in eukaryotic DNA replication and has been confirmed to be associated with the occurrence and progression of many tumors. However, the expression levels, functions, and prognostic values of MCMs in breast cancer (BC) have not been clearly and systematically explained. In this article, we studied the transcriptional levels of MCMs in BC based on the Oncomine database. Kaplan-Meier plotter was used to analyze prognostic value of MCMs in human BC patients. Furthermore, we constructed a MCM coexpression gene network and performed functional annotation analysis through DAVID to reveal the functions of MCMs and coexpressed genes. The data showed that the expression of MCM2–8 and MCM10 but not MCM1 and MCM9 was upregulated in BC. Kaplan-Meier plotter analysis revealed that high transcriptional levels of MCM2, MCM4–7, and MCM10 were significantly related to low relapse-free survival (RFS) in BC patients. In contrast, high levels of MCM1 and MCM9 predicted high RFS for BC patients. This study suggests that MCM2, MCM4–7, and MCM10 possess great potential to be valuable prognostic biomarkers for BC and that MCM1 and MCM9 may serve as potential treatment targets for BC patients.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12548-e12548
Author(s):  
Xianghou Xia ◽  
Wenjuan Yin ◽  
Jiefei Mao ◽  
Jiejie Hu ◽  
Dehong Zou ◽  
...  

e12548 Background: Pyroptosis is a type of inflammatory cell death mediated by gasdermins. Pyroptosis is critical for macrophage against pathogen infection. Recently growing evidences show that pyroptosis may affect development and progression of many cancers. We aim to explore the expression and related function of pyroptosis executioner Gasdermin D (GSDMD) in breast cancer. Methods: We investigated the expression level of GSDMD using TNM plotter and Breast Cancer landscape proteome with TCGA, GTEx and TARGET databases, and the prognostic value of GSDMD in invasive breast cancer using Kaplan-Meier plotter with TCGA, GEO and EGA databases. The treatment response prediction values of GSDMD in invasive breast were calculated using ROC-plotter with GEO database. Further validation of the prognostic value and chemotherapy response prediction value of GSDMD were carried out with immunohistochemical staining on tissues from 165 cases of breast cancer patients receiving neoadjuvant chemotherapy in our cancer center. Results: TNM plotter and breast cancer landscape proteome portal analysis shows that overall expression level of GSDMD in invasive breast cancer tissue is 1.67 folds higher than it is in breast normal tissues ( p=1.05*e-06). Expression of GSDMD in LuminalB subtype (p=0.019) and Her2 subtype(p=0.04) is significantly higher than it is in TNBC subtype. Calculations with Kaplan-Meier plotter show expression of GSDMD is negatively correlated with overall survival(OS), HR=0.61(0.4−0.95) p=0.027 and relapse free survival (RFS), HR =0.65(0.58−0.63), p=8.7*e-14 and distant metastasis free survival (DMFS) HR =0.75(0.61−0.91), p=0.0038 in breast cancer patients. ROC-plotter calculations show high GSDMD expression is a powerful endocrine therapy (AUC=0.731 p=6*e-09 ) and chemotherapy response (AUC=0.64 p=8*e-05 ) predictor based on 5-year RFS in overall breast cancer patients. Our IHC staining analysis shows consistent prognostic and chemotherapy prediction value of GSDMD expression in TNBC patients. Conclusions: In conclusion, our findings suggest that high expression of GSDMD is positively correlated with prognosis and therapeutic response in breast cancer. GSDMD is a promising prognostic marker and therapeutic response predictor in invasive breast cancer.


Pteridines ◽  
2019 ◽  
Vol 30 (1) ◽  
pp. 158-164
Author(s):  
Qingyuan Su ◽  
Qingyuan Lv ◽  
Ruijin Wu

Abstract Objective: To further explore folate receptor 1 (FOLR1) gene expression in ovarian cancer and its association with patients’ prognosis by deep mining the Oncomine and Kaplan-Meier plotter databases. Methods: FOLR1 mRNA expression data of ovarian cancer were retrieved from the Oncomine database and further analyzed by comparing tumor to healthy tissue. The prognostic value of FOLR1 in ovarian cancer was analyzed by Kaplan-Meier Plotter, an online survival analysis database. Results A total of 439 studies were included in the Oncomine database in multiple types of cancers. Of the 439 studies, there were 54 with statistical differences for the expression of FOLR1, 19 with increased expression of FOLR1 and 35 with decreased expression comparing ovarian cancer to normal ovary tissue. After searching the Oncomine database, six datasets were discovered comparing the mRNA expression in ovarian tumor to healthy tissue. FOLR1 mRNA expression in ovarian tumor was significantly higher than that of normal ovarian tissue (all p<0.05). The Kaplan-Meier Plotter database analyzed the correlation between FOLR1 expression and ovarian cancer patient’s prognosis. A significant difference of progression-free survival between FOLR1 high and low expressing groups was found in ovarian cancer patients (HR=1.14, 95%CI: 1.00-1.29, p=0.043). However, the overall survival was not statistically different between high and low FOLR1 expressing patients (HR=0.95, 95%CI: 0.84-1.09, p=0.48). Conclusion FOLR1 mRNA was found to be highly expressed in ovarian tumor compared to normal ovarian tissue. Elevated FOLR1 mRNA expression was associated with the poor progression-free survival.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15532-e15532
Author(s):  
Ramon Andrade De Mello ◽  
Dania Sofia Marques ◽  
Joana Savva-Bordalo ◽  
Monica Gomes ◽  
Joana Assis ◽  
...  

e15532 Background: Interleukine (IL) 10 –592C/A and IL8 –251T/A polymorphisms previous showed an important role in cell proliferation, cell migration and angiogenesis. Therefore, we conduct a study in order to assess the role of those genetic polymorphisms as prognostic biomarkers in epithelial ovary cancer (EOC). Methods: Design: Retrospective study from 1996 to 2010. Setting: Histological confirmed EOC patients treated at our institution. Laboratory: Genotyping of IL10–592 C/A and IL8 -251T/A were performed by PCR-RFLP. DNA samples were obtained from patients’ peripheral blood. Statistical analysis: Logistic regression were used to calculate odds ratio (OR) and 95% confidential interval (95% CI). Overall survival (OS) and progression-free-survival (PFS) were performed using Kaplan-Meier analysis. Statistical significance was considered for p < 0.05. Results: It was recruited 156 participants. Median age was 53 (16 – 80) years-old. Genotype frequency distribution for IL8-251 were T/T (50%), T/A (50%) and for IL10–592, C/C (53.8%), C/A (39.7%), A/A (6.4%). These follow genotypes were associated with lymph node, pelvic and peritoneal relapse: IL10–592C/A (OR 0.229, 95% CI: 0.055 – 0.943, p = 0.041) and IL8–251T/A (OR 6.667, 95% CI: 1.359 – 32.701, p = 0.019). In overall, IL8–251T/A genotype had higher OS than IL8-251T/T genotype: 115 versus 95 months, p = 0.010. In clear cell tumors (CCT), IL8–251T/A genotype had less OS than IL8-251T/T genotype: 92 versus 107 months, p = 0.004. To IL10–592 genotypes, OS were 104 (A/A), 107 (C/A), 103 (C/C) months, p = 0.637, and PFS were 9 (A/A), 14 (C/A), 20 (C/C) months, p = 0.057. However, in CCT, PFS for IL10–592 genotypes were 4 (A/A), 56.73 (C/A), 20 (C/C) months, p = 0.023. Conclusions: Our results suggest that IL8–251T/A polymorphism could represent a prognostic biomarker in overall EOC. IL10–592C/A polymorphisms are associated with relapse and PFS mainly in CCT. Nevertheless, furthers prospective studies are warranted in order to assess its role in pharmacogenomics framework.


2020 ◽  
Vol 28 (1) ◽  
pp. 29-38
Author(s):  
Orsolya Mártha ◽  
Daniel Balan ◽  
Daniel Porav-Hodade ◽  
Emőke Drágus ◽  
Mihai Dorin Vartolomei ◽  
...  

AbstractIntroduction: The peritumoral inflammatory reaction has a substantial importance in the oncologic outcome of bladder cancer (BC). One biomarker proven to be practical and accessible is the NLR (neutrophil-to-lymphocyte ratio) for high risk non-muscle invasive bladder cancer (NMIBC). The aim of the study was to investigate the role of NLR as a prognostic biomarker for disease recurrence, progression and survival of p Ta (pathological assesment of the primary tumor) NMIBC.Material and Methods: In our retrospective study we included 54 patients with pTa NMIBC from a total of 235 patients who underwent transurethral resection of bladder tumor (TURBT) during two consecutive years: January 2007 - December 2008 [median follow-up 106 months (interquartile range-IQR 68-116)]. Criteria for inclusion were: primary tumor, low-grade, with NLR available at 2 weeks prior to TURBT. NLR was considered altered if higher than 3.Results: The median age of the patients included was 63 years (IQR 55 - 72). Most of the patients had NLR---lt---3 (37 patients). Median EORTC (European Organization of Research and Treatment of Cancer) Recurrence Score was 4 (IQR 1-6), while EORTC Progression Score was 3 (IQR 0-6), respectively. Recurrence occurred in 8 out of 54 (14.81 %) patients and progression was identified in 2 out of 54 (3.70 %) patients with muscle-invasive BC during follow-up. NLR---gt---3 was not associated with clinical and pathological factors. In multivariable Cox regression analyses NLR as a continuous variable was an independent predictive factor for recurrence. Recurrence-free survival (RFS) Kaplan-Meier analysis did not show a statistical significance between NLR groups: 82.67% vs. 64.12%, p=0.26. Kaplan-Meier analysis showed a lower Progression-free survival (PFS) in the NLR---gt---3 group: 94.12% vs. 100%, p=0.04. During follow-up (106 months) 18 patients deceased with no impact of NLR as a prognostic factor in multivariable analyses. Kaplan-Meier overall survival (OS) analysis showed a 10-year OS of 70.27% in the low NLR group compared with 58.82% in the high NLR group, p=0.45.Conclusion: In this cohort, high NLR was associated with high recurrence rate in patients with Ta NMIBC. In low-risk NMIBC NLR could represent a valid biomarker for clinical usage regarding the intensity of follow-up schedule.


2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Yingqi Qiu ◽  
Hao Wang ◽  
Peiyun Liao ◽  
Binyan Xu ◽  
Rong Hu ◽  
...  

Abstract Background Belonging to the protein arginine methyltransferase (PRMT) family, the enzyme encoded by coactivator associated arginine methyltransferase 1 (CARM1) catalyzes the methylation of protein arginine residues, especially acts on histones and other chromatin related proteins, which is essential in regulating gene expression. Beyond its well-established involvement in the regulation of transcription, recent studies have revealed a novel role of CARM1 in tumorigenesis and development, but there is still a lack of systematic understanding of CARM1 in human cancers. An integrated analysis of CARM1 in pan-cancer may contribute to further explore its prognostic value and potential immunological function in tumor therapy. Results Based on systematic analysis of data in multiple databases, we firstly verified that CARM1 is highly expressed in most tumors compared with corresponding normal tissues, and is bound up with poor prognosis in some tumors. Subsequently, relevance between CARM1 expression level and tumor immune microenvironment is analyzed from the perspectives of tumor mutation burden, microsatellite instability, mismatch repair genes, methyltransferases genes, immune checkpoint genes and immune cells infiltration, indicating a potential relationship between CARM1 expression and tumor microenvironment. A gene enrichment analysis followed shortly, which implied that the role of CARM1 in tumor pathogenesis may be related to transcriptional imbalance and viral carcinogenesis. Conclusions Our first comprehensive bioinformatics analysis provides a broad molecular perspective on the role of CARM1 in various tumors, highlights its value in clinical prognosis and potential association with tumor immune microenvironment, which may furnish an immune based antitumor strategy to provide a reference for more accurate and personalized immunotherapy in the future.


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