scholarly journals Core Circadian Clock Proteins as Biomarkers of Progression in Colorectal Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 967
Author(s):  
María I. Aroca-Siendones ◽  
Sara Moreno-SanJuan ◽  
Jose D. Puentes-Pardo ◽  
Michela Verbeni ◽  
Javier Arnedo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Prognostic Significance ◽  
Developed Countries ◽  
Disease Diagnosis ◽  
Independent Prognostic Factor ◽  
High Expression ◽  
Incidence And Mortality ◽  
Circadian Clock Proteins ◽  
Low Expression

Colorectal cancer (CRC) is one of the most common tumours in developed countries. Although its incidence and mortality rates have decreased, its prognosis has not changed, and a high percentage of patients with CRC develop relapse (metachronous metastasis, MM, or local recurrence, LR) during their disease. The identification of these patients is very important for their correct management, but the lack of prognostic markers makes it difficult. Given the connection between circadian disruption and cancer development and progression, we aimed to analyse the prognostic significance of core circadian proteins in CRC. We measured the expression of PER1-3, CRY1-2, BMAL1 and NR1D2 in a cohort of CRC patients by immunohistochemistry (IHC) and analysed their prognostic potential in this disease. A low expression of PER2 and BMAL1 was significantly associated with metastasis at the moment of disease diagnosis, whereas a high expression of CRY1 appeared as an independent prognostic factor of MM development. A high expression of NR1D2 appeared as an independent prognostic factor of LR development after disease diagnosis. Moreover, patients with a low expression of BMAL1 and a high expression of CRY1 showed lower OS and DFS at five years. Although these markers need to be validated in larger and different ethnic cohorts, the simplicity of IHC makes these proteins candidates for personalizing CRC treatment.

scholarly journals Construction of an RNA Binding Protein-based Model for Prognosis Prediction of Colorectal Cancer

2020 ◽  
Author(s):  
Ting li ◽  
Wenjia Hui ◽  
Halina Halike ◽  
Feng Gao
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Risk Score ◽  
Rna Binding ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Gene Signature ◽  
Independent Prognostic Factor ◽  
Time Dependent ◽  
Incidence And Mortality

Abstract Background: Colorectalcancer (CRC) is a prevalent gastrointestinal tumor with high incidence and mortality. Dysregulation of RNA binding proteins (RBPs) has been found in a variety of cancers and is related to oncogenesis and progression. This study aimed to develop and validate new biomarkers related to CRC prognosis by a series of bioinformatics analysis.Methods: We mined the gene expression data of 510 CRC samples from The Cancer Genome Atlas (TCGA) database, differentially expressed genes were screened and prognosis-related genes were identified. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out. A prognosis-related gene signature was constructed by univariate and multivariate Cox analysis. Kaplan–Meier curves and time-dependent receiver operating characteristic (ROC) curves were utilized to evaluate the signature,The test set was used to validate the RBPs risk score model.Survival analysis was carried out to determine the independent prognostic significance of the signature. A nomogram combined with the gene signature was constructed.Results: A total of 224 aberrantly expressed RBPs were obtained, comprising 78 downregulated and 146 upregulatedRBPs. 13 RBPs with p < 0.005 were revealed in univariateCox regression analysis of train group, then stepwise multivariate Cox regression was applied for constituting an eight- RBP (BRCA1, TERT, TDRD7, PPARGC1A, LUZP4, CELF4, ZC3H12C, PNLDC1) signature prognostic biomarkers. Further analysis demonstrated that high risk score for patients was significantly related to poor overall survival according to the model. The area under the time-dependent receiver operator characteristic curve of the prognostic model was 0.730 at 5 years. The signature-based risk score was an independent prognostic factor in CRC patients. We also established a nomogram based on eight RBPs and internal validation in the train set, which displayed a favorable discriminating ability for Colorectal cancer.Conclusions: The established eight-RBP signature may serve as a novel independent prognostic factor that could be an important tool to predict the prognostic outcome of CRC patients. However, the specific biological mechanism needs further verification.

scholarly journals Chemokine (C-X-C motif) ligand 1 is associated with tumor progression and poor prognosis in patients with colorectal cancer

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Changhua Zhuo ◽  
Xianyi Wu ◽  
Jing Li ◽  
Dan Hu ◽  
Jinliang Jian ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Cancer Progression ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Independent Prognostic Factor ◽  
In Vitro Assays ◽  
Tumor Diameter ◽  
Cxcl1 Expression

Chemokine (C-X-C motif) ligand 1 (CXCL1) is a chemotactic cytokine known to regulate cancer progression and invasion. However, the prognostic significance of CXCL1 expression in colorectal cancer (CRC) has not been fully characterized. The present study explored the clinicopathological significance and potential role of CXCL1 in the carcinogenesis and progression of CRC. The protein expression of CXCL1 was measured immunohistochemically in tissue microarrays constructed from 276 CRC patients. CXCL1 expression levels and their associations with clinicopathological characteristics and patient survival were evaluated. The effect of CXCL1 on glycolysis was also examined. High CXCL1 expression was detected in 165 (59.8%) cases. CXCL1 expression was correlated with tumor diameter (P=0.002), T stage (P=0.044), N stage (P=0.005), M stage (P=0.001), lymphovascular invasion (P=0.010), and carcinoembryonic antigen status (P=0.019). High CXCL1 expression was validated as an independent prognostic factor for overall survival (OS) and disease-free survival (DFS) by both univariate and multivariate Cox regression analyses (both P<0.05). Experimentally, expression of CXCL1 was knocked down by stable transfected short hairpin RNA, resulting in a significantly decreased rate of glycolysis both in in vitro assays and in patients’ samples (P<0.05). Silencing the expression of CXCL1 decreased the levels of the glycolytic enzymes GLUT1, HK2, and LDHA. In conclusion, by inducing glycolysis, CXCL1 plays a crucial role in both cancer progression and metastasis in CRC patients. The CXCL1 expression level is an independent prognostic factor for both OS and DFS. Moreover, CXCL1 may serve as a new biomarker and potential therapeutic target for CRC treatment.

Identification of a new subgroup of adult acute T-lymphoblastic leukemia (T-ALL) with a very favorable outcome using low ERG and BAALC expression

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7014-7014
Author(s):  
C. D. Baldus ◽  
P. Martus ◽  
T. Burmeister ◽  
S. Schwartz ◽  
N. Goekbuget ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Favorable Outcome ◽  
High Expression ◽  
Treatment Intensification ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Low Expression

7014 Background: High expression of the oncogenic ETS transcription factor ERG is an independent adverse prognostic factor in T-ALL and acute myeloid leukemia (AML). The gene BAALC similarly shows high expression in hematopoietic progenitors, downregulation with onset of differentiation, and prognostic significance in AML. Therefore, we assessed whether combined expression of ERG and BAALC would better predict outcome in T-ALL. Methods: ERG and BAALC mRNA expression was determined by realtime RT-PCR in pretherapy bone marrow of 152 adults with newly diagnosed T-ALL treated on German ALL protocols (05/93, 06/99). Patients (pts) were designated low (n=76) or high (n=76) ERG expressers based on median ERG expression and as low (n=111) or high (n=37) BAALC grouping the lower quartiles 1–3 vs. quartile 4. HOX11 and HOX11L2 expression was determined and immunophenotyping differentiated 3 T-ALL groups (early, thymic, mature). Results: High BAALC expression correlated with immature T-ALL with a higher frequency of early T-ALL (P<0.0001), CD34 positivity (P<0.0001), co-expression of myeloid markers (CD13 and/or CD33; P=0.03), and high ERG expression (P=0.02). Pts with high BAALC had fewer complete remissions (73% vs. 89%, P=0.03) and a higher relapse rate (67% vs. 32%, P=0.01) than low BAALC pts. Excluding 33 pts that had received stem cell transplantation (SCT), high expression of ERG (P=0.002) and of BAALC (P=0.0004) was associated with inferior relapse-free survival (RFS) and overall survival (OS, ERG: P=0.004; BAALC: P=0.0001) compared to low expression of ERG and BAALC, respectively. In contrast, pts with low expression of both ERG and BAALC had the most favorable outcome (5y-RFS: low ERG/low BAALC 81% vs. high ERG and/or high BAALC 33%, P<0.0001; 5y-OS: low ERG/low BAALC 69% vs. high ERG and/or high BAALC 26%, P=0.0001). On multivariable analysis low ERG/low BAALC expression was of independent favorable prognostic significance (RFS, HR: 0.18, P=0.0003; OS, HR: 0.3, P=0.001); the only other prognostic factor was the immunophenotype. Conclusions: Low expression of both ERG and BAALC identifies T-ALL pts with a distinctly favorable long term outcome, thus detecting pts that may not benefit from further treatment intensification including SCT. No significant financial relationships to disclose.

Tumor perivascular PDGFBR as an independent prognostic factor in metastatic colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3571-3571
Author(s):  
Maja Bradic Lindh ◽  
Artur Mezheyeuski ◽  
Bengt Glimelius ◽  
Per Pfeiffer ◽  
Elin Kure ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Alkaline Phosphatase ◽  
Prognostic Factor ◽  
Normal Tissue ◽  
Performance Status ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
Independent Prognostic Factor ◽  
Phase Iii ◽  
Double Staining

3571 Background: New vessel formation is an essential factor for tumor growth and metastasis. Tumor vessels show reduced and variable pericyte coverage. Several pericyte markers have been identified, including platelet-derived growth factor receptor beta (PDGFbR), smooth muscle α-actin (ASMA) and desmin. Variability in pericyte status and its prognostic significance remains largely uncharacterized in colorectal cancer (CRC). The aim of the present study was to perform a preliminary analysis of the variability in expression of the three pericyte markers and to investigate the potential prognostic significance of perivascular PDGFbR (PV-PDGFbR). Methods: A population-based cohort was used for double-staining, performed on 100 tumors with CD34 and above-named pericyte markers. For the rest of the study a metastatic CRC (mCRC) collection from the phase III NORDIC-VII study was used. Analyses were performed on a tissue microarray with tumor material from 328 out of the 566 patients in the intention to treat population. All tumors and corresponding normal tissue were scored by immunohistochemistry (IHC) with regard to PV-PDGFbR. 255 and 97 cases were analyzed by IHC with regard to perivascular ASMA and microvessel density (MVD), respectively. Results: Analyses of the double-staining revealed independent and variable expressions of all three pericyte markers. Analyses of the NORDIC-VII cohort revealed two prognostic groups with low and high PV-PDGFbR expression. Median OS was 14.3 mo for PV-PDGFbR-low tumors (N=22) vs. 22.9 mo for PV-PDGFbR-high (N=306) tumors (HR=1.95; 95% CI 1.20-3.16; log-rank p=0.007). Multivariate analysis, including WHO performance status, alkaline phosphatase level and BRAF mutation status confirmed PV-PDGFbR as an independent prognostic factor of OS (HR=1.75; 95% CI 1.07-2.84; p=0.025). PV-PDGFbR was not significantly linked to perivascular ASMA or MVD. PV-PDGFbR in normal tissue was not associated with survival. Conclusions: CRC display a previously un-recognized variability in pericyte characteristics. Low tumor PV-PDGFbR level is associated with worse prognosis in patients with mCRC, in a manner independent of performance status, alkaline phosphatase levels and BRAF status.

scholarly journals Prognostic significance of esterase gene expression in multiple myeloma

2021 ◽  
Author(s):  
Romika Kumari ◽  
Muntasir Mamun Majumder ◽  
Juha Lievonen ◽  
Raija Silvennoinen ◽  
Pekka Anttila ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Prognostic Markers ◽  
Prognostic Significance ◽  
Genomic Variation ◽  
High Expression ◽  
Genetic Profile ◽  
Esterase Gene ◽  
Low Expression

Abstract Background Esterase enzymes differ in substrate specificity and biological function and may display dysregulated expression in cancer. This study evaluated the biological significance of esterase expression in multiple myeloma (MM). Methods For gene expression profiling and evaluation of genomic variants in the Institute for Molecular Medicine Finland (FIMM) cohort, bone marrow aspirates were obtained from patients with newly diagnosed MM (NDMM) or relapsed/refractory MM (RRMM). CD138+ plasma cells were enriched and used for RNA sequencing and analysis, and to evaluate genomic variation. The Multiple Myeloma Research Foundation (MMRF) Relating Clinical Outcomes in MM to Personal Assessment of Genetic Profile (CoMMpass) dataset was used for validation of the findings from FIMM. Results MM patients (NDMM, n = 56; RRMM, n = 78) provided 171 bone marrow aspirates (NDMM, n = 56; RRMM, n = 115). Specific esterases exhibited relatively high or low expression in MM, and expression of specific esterases (UCHL5, SIAE, ESD, PAFAH1B3, PNPLA4 and PON1) was significantly altered on progression from NDMM to RRMM. High expression of OVCA2, PAFAH1B3, SIAE and USP4, and low expression of PCED1B, were identified as poor prognostic markers (P < 0.05). The MMRF CoMMpass dataset provided validation that higher expression of PAFAH1B3 and SIAE, and lower expression of PCED1B, were associated with poor prognosis. Conclusions Esterase gene expression levels change as patients progress from NDMM to RRMM. High expression of OVCA2, PAFAH1B3, USP4 and SIAE, and low expression of PCED1B, are poor prognostic markers in MM, suggesting a role for these esterases in myeloma biology.

The Clinical and Prognostic Significance of Protein Arginine Deiminases 2 and 4 in Colorectal Cancer

Pathobiology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Mohamed Gijon ◽  
Rachael L. Metheringham ◽  
Michael S. Toss ◽  
Samantha J. Paston ◽  
Lindy G. Durrant
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Survival Time ◽  
Patient Survival ◽  
Prognostic Significance ◽  
High Expression ◽  
Related Protein ◽  
Post Translational Modification

<b><i>Introduction:</i></b> Protein arginine deiminases (PADIs) are a family of enzymes that catalyse the post-translational modification of proteins. Association between PADI expression and clinicopathology, protein expression, and outcome was determined. <b><i>Methods:</i></b> PADI2 and PADI4 expression was assessed immunohistochemically in a cohort of colorectal cancer (CRC) patients. <b><i>Results:</i></b> CRC tissues expressed variable levels of PADI2 which was mainly localised in the cytoplasm and correlated with patient survival (<i>p</i> = 0.005); high expression increased survival time from 43.5 to 67.6 months. Expression of cytoplasmic PADI2 correlated with the expression of nuclear β catenin, PADI4, and alpha-enolase. In contrast, expression of nuclear PADI2 correlated with a decrease in survival (<i>p</i> = 0.010), with high expression decreasing survival from 76.4 to 42.9 months. CRC tissues expressed variable levels of PADI4 in both the nucleus and cytoplasm. Expression of cytoplasmic PADI4 correlated with survival (<i>p</i> = 0.001) with high expression increasing survival time from 48.1 to 71.8 months. Expression of cytoplasmic PADI4 correlated with expression of nuclear β catenin, alpha-enolase (<i>p</i> ≤ 0.0001, <i>p</i> = 0.002), and the apoptotic related protein, Bcl-2. Expression of nuclear PADI4 also correlated with survival (<i>p</i> = 0.011), with high expression of nuclear PADI4 increasing survival time from 55.4 to 74 months. Expression of nuclear PADI4 correlated with p53, alpha-enolase, and Bcl-2. Multivariate analysis showed that TNM stage, cytoplasmic PADI2, and PADI4 remained independent prognostic factors in CRC. Both PADI2 and PADI4 are good prognostic factors in CRC. <b><i>Conclusion:</i></b> High expression of cytoplasmic PADI2, PADI4, and nuclear PADI4 were associated with an increase in overall survival.

Circulating Fibrinogen to Pre-albumin Ratio for Chemotherapy Efficacy Prediction and Prognosis of Colorectal Cancer Patients

2020 ◽  
Author(s):  
Hou-Qun Ying ◽  
Fan Sun ◽  
Wei Wang ◽  
Dan Cai ◽  
Ying Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Chronic Inflammation ◽  
Clinical Outcomes ◽  
Cox Regression ◽  
Independent Prognostic Factor ◽  
Low Grade ◽  
Albumin Ratio ◽  
Response To Chemotherapy ◽  
Chemotherapy Efficacy

Abstract Background Evaluating chronic inflammation in colorectal cancer (CRC) may aid in identifying patients at the highest risk of recurrence or progression, and help inform clinical treatment decisions. Here, we report the effect of fibrinogen to pre-albumin ratio (FPR) in determining response to chemotherapy and reveal outcomes in CRC patients. Methods A total of 2917 eligible CRC patients from multiple-centers were enrolled, and the outcome of these patients was obtained by three years’ follow-up. Circulating fibrinogen, albumin, pre-albumin, CEA, CA199 and FPR were detected and calculated in these patients. Kaplan-Meier curves, Cox regression, time-dependent ROC, Harrell’s concordance index, calibration and decision curves were used to investigate the role of FPR in clinical outcome of CRC patients. Results Our results reveal significantly inferior outcomes in right- than left-sided patients with advanced CRC (stage III and IV), with preoperative FPR found to be a robust and independent prognostic factor for CRC at each stage. Moreover, prognostic nomograms, including FPR, effectively predicted clinical outcomes of the patients. Furthermore, preoperative FPR was significantly associated with chemotherapy efficacy. Specifically, low-grade (FPR < 15) and medium-grade (15 ≤ FPR < 20) FPR patients exhibited complete response to chemotherapy and attenuated chemosensitivity, respectively, whereas high-grade inflammation (FPR ≥ 20) conferred resistance to the treatment. Conclusion CRC-related inflammation affects response to chemotherapy and the resultant clinical outcomes. Circulating FPR is a simple, economically-friendly and robust independent prognostic factor for effectively predicting outcomes of CRC patients. Targeting chronic inflammation and its corresponding signaling pathway, coupled with measuring FPR, presents a novel approach for clinical management of CRC.

scholarly journals Prognostic Significance of Sarcopenia in Patients with Unresectable Advanced Esophageal Cancer

2019 ◽  
Vol 8 (10) ◽  
pp. 1647 ◽  
Author(s):  
Sachiyo Onishi ◽  
Masahiro Tajika ◽  
Tsutomu Tanaka ◽  
Yutaka Hirayama ◽  
Kazuo Hara ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Japanese Patients ◽  
Independent Prognostic Factor ◽  
Cancer Center ◽  
Advanced Esophageal Cancer ◽  
Cox Regression Analysis ◽  
Group 2

The prognostic significance of sarcopenia in unresectable advanced esophageal cancer remains unclear. Our study retrospectively evaluated 176 consecutive Japanese patients with esophageal squamous cell carcinoma who had been diagnosed with unresectable advanced cancer in Aichi Cancer Center Hospital between January 2007 and December 2014. Skeletal muscle mass was calculated from abdominal computed tomography (CT) scans before treatment, and patients were divided into sarcopenic and non-sarcopenic groups. Sarcopenia was present in 101 patients (57.4%). Eighty-two patients in the sarcopenic group and 63 patients in the non-sarcopenic group died during follow-up (mean: 20.3 months). The overall survival (OS) rate was significantly lower in the sarcopenic group compared to the non-sarcopenic group (2-year OS: 9.8% vs. 23.7%, p < 0.01). Cox regression analysis revealed only pretreatment sarcopenia as an independent prognostic factor (hazard ratio (HR): 1.48, 95% confidence interval (CI): 1.04–2.10, p = 0.03). In the sarcopenic group, withdrawn cases, for whom the planned treatment was discontinued for some reason, showed a significantly lower OS rate compared to complete cases (1-year OS: 11.0% vs. 59.9%, p < 0.01). The most common reason for discontinuation was aspiration pneumonia (64.5%). Presence of sarcopenia was an independent prognostic factor for unresectable advanced esophageal cancer. Identifying the presence of sarcopenia prior to treatment may improve the prognosis.

scholarly journals Preoperative Plasma Fibrinogen and Serum Albumin Score Is an Independent Prognostic Factor for Resectable Stage II-III Gastric Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Menghui Wu ◽  
Yuchen Pan ◽  
Zhifang Jia ◽  
Yueqi Wang ◽  
Na Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Factor ◽  
Serum Albumin ◽  
Poor Prognosis ◽  
Response Rate ◽  
Prognostic Significance ◽  
Independent Prognostic Factor ◽  
The Other ◽  
Plasma Fibrinogen ◽  
Radical Gastrectomy

Background. Radical gastrectomy with D2 lymphadenectomy is recognized as the standard treatment for resectable advanced gastric cancer. Preoperative fibrinogen and albumin measurements may bring clinical benefits in terms of providing advanced notice of a poor prognosis or recurrence in patients undergoing radical resection. The aim of this study was to identify markers that are predictive of a poor prognosis prior to surgery. Methods. Eight hundred forty-two consecutive patients who underwent curative radical gastrectomy at our hospital between 2008 and 2012 were retrospectively reviewed. Based on plasma fibrinogen and serum albumin levels, preoperative fibrinogen and albumin scores (Fib-Alb scores) were investigated, and the prognostic significance was determined. Results. The patients were classified according to a Fib-Alb score of 0 (n=376), 1 (n=327), or 2 (n=139). When the correlation between the response rate and the change in the Fib-Alb score was investigated, the response rate was significantly lower in patients with an increased Fib-Alb score than in the other patients. In the survival analysis, patients in the Fib-Alb high-score group exhibited significantly worse recurrence-free survival (RFS) (P=0.030) than patients in the other groups. A multivariate analysis using clinical stage and the change in the Fib-Alb score as covariates revealed that a change in the Fib-Alb score (Fib-Alb score 1, HR: 1.31, 95% CI: 1.03-1.66, P=0.028; Fib-Alb score 2, HR: 1.61, 95% CI: 1.20-2.17, P=0.001) was a significant independent predictive factor for RFS. Conclusions. The prognosis of patients with high fibrinogen and low albumin levels is poor. The Fib-Alb score was shown to be an independent prognostic factor for postoperative recurrence in gastric cancer patients who underwent radical gastrectomy.

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