scholarly journals Protein Arginine Deiminase 2 and 4 (PAD2 & PAD4) are independent predictors of good prognosis in colorectal cancer

2020 ◽  
Author(s):  
Mohamed Gijon ◽  
Rachael L Metheringham ◽  
Samantha J Paston ◽  
Lindy G Durrant
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factors ◽  
Survival Time ◽  
Patient Survival ◽  
Prognostic Significance ◽  
Good Prognosis ◽  
Arginine Deiminase ◽  
High Expression ◽  
Post Translational Modification ◽  
Protein Arginine Deiminase

Objective: Protein arginine deiminase (PADs) are a family of enzymes that catalyse the post translational modification (PTM) of proteins. In this study the prognostic significance of PAD2 and PAD4 in colorectal cancer (CRC) was assessed. Design: PAD2 and PAD4 expression was assessed immunohistochemically in a cohort of CRC patients. Association between PAD expression with clinicopathology, protein expression and outcome was determined. Results: CRC tissues expressed variable levels of PAD2 which was mainly localised in the cytoplasm and correlated with patient survival (p=0.005); high expression increased survival time from 43.5 to 67.6 months. Expression of cytoplasmic PAD2 correlated with expression of nuclear β catenin, PAD4 and alpha-enolase. In contrast expression of nuclear PAD2 correlated with a decrease in survival (p=0.010), with high expression decreasing survival from 76.4 to 42.9 months. CRC tissues expressed variable levels of PAD4 in both the nucleus and cytoplasm. Expression of cytoplasmic PAD4 correlated with survival (p=0.001) with high expression increasing survival time from 48.1 to 71.8 months. Expression of cytoplasmic PAD4 correlated with expression of, nuclear β catenin, alpha-enolase (p≤ 0.0001, p=0.002) and the apoptotic related protein, Bcl-2. Expression of nuclear PAD4 also correlated with survival (p=0.011) with high expression of nuclear PAD4 increasing survival time from 55.4 to 74 months. Expression of nuclear PAD4 correlated with p53, alpha-enolase and Bcl-2. Multivariate analysis showed that TNM stage and cytoplasmic PAD2 and PAD4 remained independent prognostic factors in CRC. Conclusion: Both PAD2 and PAD4 are good prognostic factors in CRC.

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.

scholarly journals Colorectal Cancer and Basement Membranes: Clinicopathological Correlations

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Charalampos C. Mylonas ◽  
Andreas C. Lazaris
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factors ◽  
Patient Survival ◽  
Prognostic Significance ◽  
Tumor Stage ◽  
Basement Membranes ◽  
Therapeutic Approaches ◽  
The Third ◽  
Clinicopathological Correlations ◽  
Treatment Prognosis

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second in females. In 2008, an estimated 1.2 million people were diagnosed with and 608,700 people died of CRC. Besides diagnosis and treatment, prognosis is an important matter for cancer patients. Today, clinicopathological correlations have many applications in cancer prognostication. Examples include the prediction of the medium patient survival and the screening for patients suitable for specific therapeutic approaches. Apart from traditional prognostic factors, such as tumor stage and grade, new markers may be useful in clinical practice. Possible markers may result from the study of basement membranes (BMs). BM seems to play a role in the pathogenesis of colorectal cancer, so BM alterations may have prognostic significance as well. The purpose of this review is to briefly describe BMs and their relationship with CRC, in the aspect of clinicopathological correlations.

Analysis of RGS2 expression and prognostic significance in stage II and III colorectal cancer

2010 ◽  
Vol 30 (6) ◽  
pp. 383-390 ◽  
Author(s):  
Zheng Jiang ◽  
Zhimin Wang ◽  
Ye Xu ◽  
Beilan Wang ◽  
Wei Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mrna Expression ◽  
Survival Time ◽  
Cell Lines ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Rank Test ◽  
Clinicopathological Factors ◽  
Real Time Quantitative Pcr

The role of RGS2 (regulator of G-protein signalling 2) has been studied in several tumours. The purpose of the present study is to investigate the correlations between clinicopathological factors and patients' survival time and RGS2 expression in stage II and III CRC (colorectal cancer) patients. Real-time quantitative PCR was performed in 36 CRC tissues with recurrence and 28 without recurrence, and in three CRC-metastasis-derived cell lines (SW620, LoVo and Colo205) and 3 primary-CRC-derived ones (SW480, Caco-2 and HCT116) to examine RGS2 mRNA expression. In addition, to provide visualized evidence for RGS2 mRNA expression, random CRC samples were also performed with RT–PCR (reverse transcription–PCR). RGS2 protein was detected by immunostaining in 118 paraffin-embedded specimens, and the correlations between clinicopathological factors and survival time and RGS2 expression were analysed. We found that RGS2 mRNA was down-regulated both in CRC tissues with recurrence and metastasis-derived cell lines, and the expression level of RGS2 was unrelated to gender, age, tumour grade, or lymphovascular or perineural invasion. However, it was positively related to disease-free survival time (P<0.05). Furthermore, low RGS2 expression indicated a poorer survival rate (P<0.05, log-rank test). Multivariate analysis also showed that weak RGS2 protein expression was an independent adverse prognosticator in CRC (P<0.05). Taken together, we suggested that down-regulation of RGS2 might play an important role in CRC metastasis and predict poor prognosis in stage II and III CRC patients.

How long have we got? The accuracy of physicians’ estimates and scenarios for survival time in 898 women with recurrent ovarian cancer (ROC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5549-5549
Author(s):  
Felicia Roncolato ◽  
Rachel O'Connell ◽  
Florence Joly ◽  
Anne Lanceley ◽  
Felix Hilpert ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Prognostic Factors ◽  
Survival Time ◽  
Cox Model ◽  
A Priori ◽  
Prognostic Significance ◽  
Recurrent Ovarian Cancer ◽  
Worst Case ◽  
Cox Models ◽  
Platinum Sensitive

5549 Background: Predicting, formulating, and communicating prognosis in women with ROC is difficult. Best-case, worst-case, and typical scenarios for survival time based on simple multiples of an individual’s expected survival time (EST) estimated by their oncologist have proven accurate and useful in a range of advanced cancers. We sought the accuracy and prognostic significance of such estimates in the GCIG Symptom Benefit Study: a multinational, prospective cohort study of women with ROC (platinum resistant and potentially platinum sensitive ROC who have had more than 2 lines of chemotherapy). Methods: Oncologists estimated EST at baseline for each woman they recruited to the GCIG Symptom Benefit Study in 11 countries. We hypothesised a priori that oncologists’ estimates of EST would be unbiased (equal proportions [approximately 50%] of women living longer versus shorter than their EST), imprecise ( < 33% living within 0.75 to 1.33 times their EST), and provide accurate scenarios for survival time (approximately 10% dying within ¼ of their EST, 10% living longer than 3 times their EST, and 50% living from half to double their EST). We also hypothesised that oncologists’ estimates of EST would be independently significant predictors of survival in a multivariable Cox model adjusting for prognostic factors established in previous studies. Results: Oncologists’ individualised estimates of EST in 898 women with ROC were unbiased (55% of women lived longer than their EST) and imprecise (23% lived within 0.75 to 1.33 times their EST). Scenarios for survival time based on oncologists’ estimates of EST were remarkably accurate: 7% of women died within ¼ of their EST, 13% lived longer than 3 times their EST, and 53% lived from half to double their EST. The median EST was 12 months (range 3-70), and median observed was 12.7 months. Oncologists’ estimates of EST were independently significant predictors of overall survival (HR 0.96, CI 0.94-0.98, p < 0.0001) in Cox models accounting for previously established prognostic factors. Conclusions: Oncologists’ estimates of EST were unbiased, imprecise, and independently significant predictors of survival time. Best-case, worst-case and typical scenarios based on simple multiples of EST were remarkably accurate, and provide a useful approach for predicting, formulating, and explaining prognosis in women with recurrent ovarian cancer. Clinical trial information: ACTRN: 12607000603415.

Low expression of CysLT1R and high expression of CysLT2R mediate good prognosis in colorectal cancer

2010 ◽  
Vol 46 (4) ◽  
pp. 826-835 ◽  
Author(s):  
Cecilia Magnusson ◽  
Maryna Mezhybovska ◽  
Ester Lörinc ◽  
Eva Fernebro ◽  
Mef Nilbert ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Good Prognosis ◽  
High Expression ◽  
Low Expression

scholarly journals Expression and prognostic significance of MT1 isoforms in clear cell renal cell carcinoma

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 280
Author(s):  
Xiaohua Niu ◽  
Ling Deng ◽  
Chaoming Tang ◽  
Dexiang Zhuo
Keyword(s):  
Mrna Expression ◽  
Survival Time ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Cancer ◽  
Tumor Biology ◽  
Prognostic Significance ◽  
High Expression ◽  
Expression Levels ◽  
Mrna Expression Levels

Metallothioneins (MTs), a family of low-weight cysteine-rich proteins, play key roles in tumor biology, such as proliferation, differentiation, apoptosis, and drug resistance. Clinical studies have demonstrated that deregulation of MTs in various types of solid cancers. However, a comprehensive overview of MT1 isoforms expression and clinical relevance in clear cell renal cell cancer (ccRCC) is lacking. The present study explored mRNA expression levels and prognostic values of MT1 isoforms in ccRCC tissues using The Cancer Genome Atlas (TCGA), Gene Expression Profiling and Interactive Analysis (GEPIA) and Oncomine database. The study observed that mRNA expression levels of six members of MT1 isoforms decreased in renal cancer tumor tissues compared with normal tissues. We further found that high-expression of MT1G, MT1H, MT1F and MT1X was related with poor overall survival time in ccRCC patients and high-expression of MT1G, MT1F and MT1X were inversely associated with disease-free survival time in ccRCC patients. Based on the correlation analysis, MT1G was identified to be co-expressed with MT1H and MT1F in ccRCC tissues. These findings suggested that MT1 isoforms mRNA may serve as diagnostic and prognostic markers for ccRCC.

scholarly journals High expression of PD-L1 Predicts Worse Overall Survival in the Cavitary Lung Adenocarcinoma

2020 ◽  
Author(s):  
Jiangyong Liu ◽  
Mingming Gu ◽  
Yang Xue ◽  
Yong Ren ◽  
Wencai Huang
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Prognostic Significance ◽  
Tumor Infiltrating Lymphocytes ◽  
Good Prognosis ◽  
High Expression ◽  
Quantitative Immunofluorescence ◽  
L1 Protein ◽  
Infiltrating Lymphocytes

Abstract Objective Solitary cavitary lung cancer is one of the rare types of lung cancer. Generally, the relationship between cavitary lung adenocarcinoma and immunotherapy remains unknown. We aimed to assess programmed cell death ligand-1(PD-L1) expression and CD8-positive (CD8+) tumor infiltrating lymphocytes (TILs) density, and evaluate their prognostic significance of patients with cavitary lung adenocarcinoma (LUAD). Methods 65 patients diagnosed as solitary cavitary LUAD were included in this study, 30 cases of noncavitary LUAD patients were collected as controls, and their specimens from surgery or biopsy were obtained. Expression of PD-L1 protein and CD8+ TILs were detected by traditional immunohistochemistry and multiplex quantitative immunofluorescence technology. The correlations of PD-L1 expression and clinicopathological features, including overall survival in cavitary LUAD patients was evaluated based on the follow-up data. Results Overexpression of PD-L1 protein was detected in the tumor tissues of cavitary LUAD patients compared to the noncavitary LUAD controls. PD-L1 expression level was significantly related to the lymph node (P = 0.001), TNM stage (P = 0.024), and CD8+ TIL status (rs= -0.272, P = 0.025). High PD-L1 expression predicted high mortality rate (P < 0.001), but CD8+ TIL group showed better survival in cavitary LUAD patients (P = 0.011). This phenotype with high PD-L1 expression and low CD8 + TIL predicted poorer overall survival of the patients with cavitary LUAD, compared to the other phenotypes. Moreover, CD8+ TIL was an independent good prognosis factor. Conclusion We firstly demonstrated that PD-L1 is upregulated in the cavitary LUAD patients, and high expression of PD-L1 negatively correlated with CD8 T cell infiltrating status. High PD-L1 expression and low CD8 + TIL can predict poorer overall survival of the patients with cavitary LUAD.

scholarly journals Association between c-Met and lymphangiogenic factors in patients with colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22199-e22199
Author(s):  
Kyoungha Kim ◽  
Hanjo Kim ◽  
Min Young Lee ◽  
Tae Sung Ahn ◽  
Jina Yun ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Tumor Cells ◽  
Cancer Metastasis ◽  
Prognostic Significance ◽  
Indirect Evidence ◽  
High Expression ◽  
Lymph Node Status ◽  
Vegf Receptor

e22199 Background: Lymphangiogenesis plays an important role in cancer metastasis. Although animal models show a strong relationship between lymphangiogenesis and lymph node metastasis and survival, the clinical significance of lymphangiogenesis in colorectal cancer (CRC) remains uncertain. The goal of this study was to evaluate the association between c-Met and lymphangiogenic factors and to elucidate their prognostic significance for patients with CRC. Methods: A total of 379 tissue samples were obtained from surgically resected specimens from patients with CRC in Soonchunhyang University Cheonan Hospital between January 2002 and December 2010. The expressions of c-Met, vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, and podoplanin were examined by immunohistochemistry. The expression of each marker and clinical factors were analyzed. Results: Three hundred and one of 379 (79.4%) tissues had c-Met expression. High expression of c-Met in tumor cells was significantly associated with high expression of VEGF-C (P < .001) and VEGFR-3 (P = .001). But, there was no statistically significant association with podoplanin (P = .587) and VEGF-D (P = .096). Of the 103 evaluable patients, expression of c-Met in tumor cells was significantly associated with advanced clinical stage (P = .020), positive lymph node status (P = .038), and high expression of VEGF-C (P = .020). But, there was no statistically significant association with podoplanin (P = .518), VEGFR-3 (P = .085), VEGF-D (P = .203), and overall survival (P = .360). Conclusions: Our results provide indirect evidence for an association and possible regulatory link of c-Met with the lymphangiogenic factors. But, c-Met expression in patients with CRC are not prognostic indicator for overall survival in this retrospective study.

scholarly journals Correlation Between Tumor-Associated Macrophage and Immune Checkpoint Molecule Expression and Its Prognostic Significance in Cutaneous Melanoma

2020 ◽  
Vol 9 (8) ◽  
pp. 2500 ◽  
Author(s):  
Young Jae Kim ◽  
Chong Hyun Won ◽  
Mi Woo Lee ◽  
Jee Ho Choi ◽  
Sung Eun Chang ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Immune Checkpoint ◽  
Cutaneous Melanoma ◽  
Prognostic Significance ◽  
High Expression ◽  
Immune Checkpoint Molecules ◽  
Tumor Associated Macrophage ◽  
Cd163 Expression ◽  
Checkpoint Molecule ◽  
Cluster Of Differentiation

The association between tumor-associated macrophages (TAMs) and the expression of immune checkpoint molecules has not been well described in cutaneous melanoma. We evaluated the correlations between the expression of markers of TAMs, cluster of differentiation 163 (CD163), and immune checkpoint molecules, programmed cell death protein-1 (PD-1), and lymphocyte activating gene-3 (LAG-3). We also determined their relationships with the clinicopathological features and disease outcomes in melanoma. Diagnostic tissues collected from melanoma patients were evaluated using immunohistochemistry for CD163, PD-1, and LAG-3 expression. CD163 expression positively correlated with PD-1 and LAG-3 expression. High expression of both CD163 and PD-1 expressions was significantly associated with negative prognostic factors and worse prognosis than high expression of the single markers. High co-expression of CD163 and LAG-3 was associated with poor clinicopathological indexes of melanoma and worse survival compared to the high expression of the single markers. The expression of immune checkpoint molecules PD-1 and LAG-3 positively correlated with the M2-TAM density in melanoma tissue. Simultaneous high M2-TAM density and immune checkpoint molecules expression acted as independent poor prognostic factors in cutaneous melanoma.

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