scholarly journals High Expression of MMP-9 in Primary Tumors and High Preoperative MPO in Serum Predict Improved Prognosis in Colorectal Cancer with Operable Liver Metastases

Oncology ◽  
2020 ◽  
pp. 1-17
Author(s):  
Reetta Peltonen ◽  
Jaana Hagström ◽  
Taina Tervahartiala ◽  
Timo Sorsa ◽  
Caj Haglund ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Tumor Tissue ◽  
Prognostic Significance ◽  
Colorectal Tumor ◽  
High Expression ◽  
Enzyme Linked Immunosorbent Assay ◽  
Primary Tumors ◽  
Cox Regression Analysis ◽  
Postoperative Serum

<b><i>Introduction:</i></b> The liver metastases of colorectal cancer (CRC) can be surgically treated in selected cases, with continuously improving results. Matrix metalloproteinases (MMPs) contribute to cancer invasion by degrading the extracellular matrix, and elevated levels of MMP-2, MMP-8, and MMP-9 have been detected in several malignancies. Myeloperoxidase (MPO) is a mediator of tissue damage that can oxidatively activate latent MMPs. We evaluated the prognostic value of MMP-2, MMP-8, and MMP-9 in tissue samples of primary tumors and liver metastases and the pre- and postoperative serum levels of MMP-8, MMP-9, and MPO in CRC patients undergoing liver resection. <b><i>Methods:</i></b> Tissue and serum samples were obtained from 111 patients who had primary colorectal tumors and their liver metastases surgically treated at the Helsinki University Hospital between 1988 and 2007. Tissue expression of MMP-2, MMP-8, and MMP-9 in primary tumors and liver metastases was evaluated by immunohistochemistry. Pre- and postoperative serum concentrations of MMP-8, MMP-9, and MPO were determined using a time-resolved immunofluorometric assay or commercially available enzyme-linked immunosorbent assay kits. Clinical data were retrieved from patient records and the Central Statistical Office of Finland. Associations with disease-free survival (DFS) and overall survival (OS) were estimated using Cox regression analysis and the Kaplan-Meier method. <b><i>Results:</i></b> High expression of MMP-9 in colorectal tumor tissue was associated with better DFS (<i>p</i> = 0.010), and high preoperative MPO in serum with improved DFS and OS (<i>p</i> &#x3c; 0.001 and <i>p</i> = 0.014, respectively). The prognostic significance varied according to gender, age, and the synchronicity of liver metastases. <b><i>Conclusion:</i></b> Low preoperative MPO in serum might identify patients at high risk of recurrence and death after resection of colorectal liver metastases. Elevated preoperative MPO and high expression of MMP-9 in colorectal tumor tissue indicate an improved prognosis. The use of these biomarkers should be adjusted according to clinical characteristics.

scholarly journals Discordance of KRAS Mutational Status between Primary Tumors and Liver Metastases in Colorectal Cancer: Impact on Long-Term Survival Following Radical Resection

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2148
Author(s):  
Francesco Ardito ◽  
Francesco Razionale ◽  
Lisa Salvatore ◽  
Tonia Cenci ◽  
Maria Vellone ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Primary Tumor ◽  
Kras Mutation ◽  
Colorectal Tumor ◽  
Term Survival ◽  
Primary Tumors ◽  
Mutation Status ◽  
Primary Colorectal Tumor ◽  
Kras Mutation Status

If KRAS mutation status of primary colorectal tumor is representative of corresponding colorectal liver metastases (CRLM) mutational pattern, is controversial. Several studies have reported different rates of KRAS discordance, ranging from 4 to 32%. Aim of this study is to assess the incidence of discordance and its impact on overall survival (OS) in a homogenous group of patients. KRAS mutation status was evaluated in 107 patients resected for both primary colorectal tumor and corresponding CRLM at the same institution, between 2007 and 2018. Discordance rate was 15.9%. Its incidence varied according to the time interval between the two mutation analyses (p = 0.025; Pearson correlation = 0.2) and it was significantly higher during the first 6 months from the time of primary tumor evaluation. On multivariable analysis, type of discordance (wild-type in primary tumor, mutation in CRLM) was the strongest predictor of poor OS (p < 0.001). At multivariable logistic regression analysis, the number of CRLM >3 was an independent risk factor for the risk of KRAS discordance associated with the worst prognosis (OR = 4.600; p = 0.047). Results of our study suggested that, in the era of precision medicine, possibility of KRAS discordance should be taken into account within multidisciplinary management of patients with metastatic colorectal cancer.

Tumor-Infiltrating FOXP3+ T Regulatory Cells Show Strong Prognostic Significance in Colorectal Cancer

2009 ◽  
Vol 27 (2) ◽  
pp. 186-192 ◽  
Author(s):  
Paul Salama ◽  
Michael Phillips ◽  
Fabienne Grieu ◽  
Melinda Morris ◽  
Nik Zeps ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colonic Mucosa ◽  
Tumor Tissue ◽  
Early Stage ◽  
Prognostic Significance ◽  
High Density ◽  
Prognostic Indicators ◽  
Normal Colonic Mucosa ◽  
Solid Cancer ◽  
Histopathologic Features

Purpose To determine the prognostic significance of FOXP3+ lymphocyte (Treg) density in colorectal cancer compared with conventional histopathologic features and with CD8+ and CD45RO+ lymphocyte densities. Patients and Methods Tissue microarrays and immunohistochemistry were used to assess the densities of CD8+, CD45RO+, and FOXP3+ lymphocytes in tumor tissue and normal colonic mucosa from 967 stage II and stage III colorectal cancers. These were evaluated for associations with histopathologic features and patient survival. Results FOXP3+ Treg density was higher in tumor tissue compared with normal colonic mucosa, whereas CD8+ and CD45RO+ cell densities were lower. FOXP3+ Tregs were not associated with any histopathologic features, with the exception of tumor stage. Multivariate analysis showed that stage, vascular invasion, and FOXP3+ Treg density in normal and tumor tissue were independent prognostic indicators, but not CD8+ and CD45RO+. High FOXP3+ Treg density in normal mucosa was associated with worse prognosis (hazard ratio [HR] = 1.51; 95% CI, 1.07 to 2.13; P = .019). In contrast, a high density of FOXP3+ Tregs in tumor tissue was associated with improved survival (HR = 0.54; 95% CI, 0.38 to 0.77; P = .001). Conclusion FOXP3+ Treg density in normal and tumor tissue had stronger prognostic significance in colorectal cancer compared with CD8+ and CD45RO+ lymphocytes. The finding of improved survival associated with a high density of tumor-infiltrating FOXP3+ Tregs in colorectal cancer contrasts with several other solid cancer types. The inclusion of FOXP3+ Treg density may help to improve the prognostication of early-stage colorectal cancer.

scholarly journals Prognostic Significance and Gene Co-Expression Network of PLAU and PLAUR in Gliomas

2022 ◽  
Vol 11 ◽  
Author(s):  
Junhong Li ◽  
Huanhuan Fan ◽  
Xingwang Zhou ◽  
Yufan Xiang ◽  
Yanhui Liu
Keyword(s):  
Cox Regression ◽  
Prognostic Significance ◽  
High Expression ◽  
Lower Grade ◽  
Tumor Type ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Online Databases ◽  
Type Plasminogen Activator ◽  
Primary Glioma

The urokinase-type plasminogen activator(PLAU) and its receptor PLAUR participate in a series of cell physiological activities on the extracellular surface. Abnormal expression of PLAU and PLAUR is associated with tumorigenesis. This study aims to evaluate the prognostic value of PLAU/PLAUR transcription expression in glioma and to explore how they affect the generation and progression of glioma. In this study, online databases are applied, such as Oncomine, GEPIA, CGGA, cBioPortal, and LinkedOmics. Overexpression of PLAU/PLAUR was found to be significantly associated with clinical variables including age, tumor type, WHO grade, histology, IDH-1 mutation, and 1p19q status. PLAU and PLAUR had a high correlation in transcriptional expression levels. High expression of PLAU and PLAUR predicted a poor prognosis in primary glioma and recurrent glioma patients, especially in lower grade gliomas. Cox regression analysis indicated that high expression of PLAU and PLAUR were independent prognostic factors for shorter overall survival in glioma patients. In gene co-expression network analysis PLAU and PLAUR and their co-expression genes were found to be involved in inflammatory activities and tumor-related signaling pathways. In conclusion, PLAU and PLAUR could be promising prognostic biomarkers and potential therapeutic targets of glioma patients.

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.

CIP4 Expression is Associated With The Prognosis in Colorectal Cancer

2020 ◽  
Author(s):  
Keqian Zhang ◽  
Tianqi Mao ◽  
Zhicheng He ◽  
Xiaojiao Wu ◽  
Yu Peng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Lymphatic Invasion ◽  
Chi Square ◽  
Interacting Protein ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Chi Square Test ◽  
Student’S T

Abstract Background: This study was conducted to detect the expression of Cdc42 interacting protein 4 (CIP4) in patients with colorectal cancer (CRC), and explore the role of CIP4 in prognosis of CRC patients.Methods: The expression of CIP4 mRNA was determined by quantitative real-time PCR (qRT-CPR) and compared by student’s t-test between groups. Relationships of clinical characteristics and CIP4 expression were analyzed by Chi-square test. Kaplan-Meier curves were used to estimate the overall survival of CRC patients. And Cox regression analysis was conducted to identify the prognostic biomarkers for CRC patients.Results: The qRT-PCR results showed that CRC tissues were detected with significantly high CIP4 mRNA expression compared with adjacent normal controls (P<0.0001). The overexpression of CIP4 in CRC tissues was influenced by distant metastasis (P=0.021), lymphatic invasion (P=0.012) and TNM stage (P=0.006). But, other clinical factors including age, gender, differentiation and tumor site were proved to have no obvious effects on CIP4 expression (all, P>0.05). The survival curves showed that patients with high CIP4 expression generally lived shorter than those with low CIP4 expression (P<0.001). In addition, the multivariate analysis revealed that differentiation (P=0.044, HR=1.631, 95%CI=1.013-2.626) and CIP4 expression (P=0.000, HR=5.283, 95%CI=3.138-8.893) were of great prognostic significance for CRC patients.Conclusion: Taken together, up-regulation of CIP4 in CRC tissues represented poor prognosis for patients.

scholarly journals Tumor Infiltration by OX40+ Cells Enhances the Prognostic Significance of CD16+ Cell Infiltration in Colorectal Cancer

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482090338
Author(s):  
Fabian Haak ◽  
Isabelle Obrecht ◽  
Nadia Tosti ◽  
Benjamin Weixler ◽  
Robert Mechera ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Cell ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Tumor Necrosis Factor Receptor ◽  
Tissue Microarrays ◽  
Cell Infiltration ◽  
Prognostic Impact ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Objectives: Analysis of tumor immune infiltration has been suggested to outperform tumor, node, metastasis staging in predicting clinical course of colorectal cancer (CRC). Infiltration by cells expressing OX40, a member of the tumor necrosis factor receptor family, or CD16, expressed by natural killer cells, monocytes, and dendritic cells, has been associated with favorable prognosis in patients with CRC. We hypothesized that assessment of CRC infiltration by both OX40+ and CD16+ cells might result in enhanced prognostic significance. Methods: Colorectal cancer infiltration by OX40 and CD16 expressing cells was investigated in 441 primary CRCs using tissue microarrays and specific antibodies, by immunohistochemistry. Patients’ survival was evaluated by Kaplan-Meier and log-rank tests. Multivariate Cox regression analysis, hazard ratios, and 95% confidence intervals were also used to evaluate prognostic significance of OX40+ and CD16+ cell infiltration. Results: Colorectal cancer infiltration by OX40+ and CD16+ cells was subclassified into 4 groups with high or low infiltration levels in all possible combinations. High levels of infiltration by both OX40+ and CD16+ cells were associated with lower pT stage, absence of peritumoral lymphocytic (PTL) inflammation, and a positive prognostic impact. Patients bearing tumors with high infiltration by CD16+ and OX40+ cells were also characterized by significantly longer overall survival, as compared with the other groups. These results were confirmed by analyzing an independent validation cohort. Conclusions: Combined infiltration by OX40+ and CD16+ immune cells is an independent favorable prognostic marker in CRC. The prognostic value of CD16+ immune cell infiltration is significantly improved by the combined analysis with OX40+ cell infiltration.

Prognostic significance of tumor stromal and epithelial claudin 2 in metastatic colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3597-3597
Author(s):  
Artur Mezheyeuski ◽  
Tormod Kyrre Guren ◽  
Bengt Glimelius ◽  
Per Pfeiffer ◽  
Elin Kure ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Alkaline Phosphatase ◽  
Cancer Cells ◽  
Tumor Tissue ◽  
Primary Cultures ◽  
Prognostic Significance ◽  
Tumor Stroma ◽  
Phase Iii ◽  
Rank Test ◽  
Worse Prognosis

3597 Background: Tight junctions (TJ) are the most apical epithelial cell–cell adhesions. Claudin super-family trans-membrane proteins, including claudin 2 (cl2), are important components of TJs. Expression of cl2 has been reported to be elevated in colorectal cancer (CRC) and its up-regulation increases tumorigenicity of CRC cells in vitro. The aim of this study was to analyze the prognostic significance of cl2 in CRC. Methods: A tissue microarray (TMA) from the stage IV CRC patients of the phase III NORDIC-VII study was used. Cl2 IHC staining was evaluated in a semi-quantitative manner in cancer cells (cl2-C) and in the tumor stroma (cl2-S). Primary fibroblasts were established from human CRC tumor tissue and non-tumor colon tissue, and evaluated by immunoblotting. Results: Analyses of the TMA derived from the NORDIC-VII cohort revealed that cancer cell expression and tumor stroma expression of cl2 was associated with shorter OS in a Log-Rank test for trend (cl2-C, n=315, p=0.018; cl2-S, n=319, p=0.020). Expression of cl2-S, but not cl2-C was prognostic in multivariate analysis including WHO performance status, alkaline phosphatase level and BRAF mutation status (HR=1.30; 95% CI 1.08-1.56; p=0.006). When cl2-C and cl2-S expression was combined the prognostic significance was increased. The group with high cl2-C and high cl2-S (N=182), when compared with the rest of the cases (n=129), displayed a worse prognosis in terms of OS (19.1 mo vs 27.2 mo; p=0.003) in univariate analyses (HR=1.55, 95% CI 1.16-2.08, p=0.003) and in multivariate analyses (HR=1.52, 95% CI 1.13-2.05, p=0.006). Immunoblotting analysis of primary cultures of fibroblasts confirmed cl2 expression in fibroblasts from CRC tissue and from non-tumor tissue, with higher expression observed in the tumor fibroblasts. Conclusions: CRC display a previously un-reported stromal expression of cl2 of prognostic significance. High cl2-S is associated with worse prognosis in patients with metastatic CRC, in a manner independent of WHO status, alkaline phosphatase levels and BRAF status. Furthermore, high expression of cl2 in both cancer cells and the tumor stroma is also associated with poor prognosis.

scholarly journals Short-term results after minimally invasive and open liver resection for liver metastases of colorectal cancer: a single center experience

2018 ◽  
Vol 46 (6) ◽  
pp. 584-591
Author(s):  
M. G. Efanov ◽  
R. B. Alikhanov ◽  
V. V. Tsvirkun ◽  
I. V. Kazakov ◽  
P. P. Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Resection ◽  
Minimally Invasive ◽  
Liver Metastases ◽  
Surgical Margin ◽  
Colorectal Metastases ◽  
Single Center ◽  
Open Resection ◽  
Tumor Spread ◽  
Primary Tumors

Rationale: Until now, safety of minimally invasive liver resection (MILR) has not been studied sufficiently.Aim: To assess immediate results of MILR and open type resections in patients with colorectal metastases, performed in the Russian center of surgical hepatology specialized at implementation of minimally invasive techniques.Materials and мethods: This was a retrospective observational case-control study. Patients who underwent surgery for isolated liver metastases of colorectal cancer in a  single center from October 2013 to February 2018 were included into the study.Results: As per December 2017, over 500 resections have been performed in the study center, including 226 MILR. One hundred two patients underwent open resection and MILR for colorectal metastases. From 83 patients enrolled into the study, 51 (61%) had MILR, including 7 robotic MILR. The open resection and MILR groups did not differ in terms of gender, age, ASA score, primary tumors location and stage by the time of primary intervention. There were no between-group differences for factors that determine the tumor spread and influence the resection problems, i.e. the difficulty index of MILR, rate of anatomic resection, resection of complex segments, vascular involvement, size and number of metastases, multiple liver lesions and bilobar metastases. No difference was found for immediate outcomes in terms of frequency of the free surgical margin > 2 mm, rate of the Pringle maneuver implementation, duration of the procedure, blood components transfusion, severe complications (Clavien-Dindo Grade > II), and time in intensive care unit. Compared to open procedures, MILR were associated with significantly less blood loss: 583 (50–3000) mL vs. 308 (0–3300) mL (p = 0.012), respectively, and shorter duration of hospital stay: 10 (4–29) days vs. 9 (4–29) days (р < 0.001), respectively.Conclusion: In a specialized surgical hepatology center, MILR can be performed equally to complex open procedures without changes in the rates and types of complications, but with an improvement of immediate outcomes.

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