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 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.

scholarly journals Clinicopathological Characteristics and Prognostic Factors in Axial Chondroblastomas: A Retrospective Analysis of 61 Cases and Comparison with Extra-Axial Chondroblastomas

2022 ◽  
Author(s):  
Bo-Wen Zheng ◽  
Bo-Yv Zheng ◽  
Hua-Qing Niu ◽  
Xiao-Bin Wang ◽  
Guo-Hua Lv ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Clinicopathological Characteristics ◽  
Motor Dysfunction ◽  
Surrounding Tissue ◽  
Wide Resection ◽  
Tissue Specimens

Abstract Background The clinical characteristics and prognostic factors of axial chondroblastoma (ACB) are still poorly understood. Purpose To characterize clinicopathological characteristics in a large ACB cohort and investigate their correlation with survival. We also sought to compare these results with extra-axial CB (EACB). Methods Our institution's local database was retrospectively reviewed and included a total of 132 CB patients, including 61 ACB patients and 71 EACB patients. Immunohistochemistry was used to assess the expression levels of Vimentin (Vim), S100, and cytokeratin (CK) on tumor cells in 132 tissue specimens. Results Overall, ACB and EACB had similar characteristics, except for older age and tumor size, as well as higher Vim expression, incidence of surrounding tissue invasion and postoperative sensory or motor dysfunction. Whereas wide resection and absence of invasion of surrounding tissues were consistently associated with favorable survival in the ACB and EACB cohorts in univariate analysis, most parameters showed differential prognostic significance between the 2 groups. Significant prognostic factors for local recurrence-free survival in multivariate analysis included the type of resection and chicken-wire calcification in the ACB cohort. Multivariate analysis of overall survival demonstrated that the type of resection was a significant predictor in the ACB cohort, whereas the type of resection and postoperative sensory or motor dysfunction were predictive of overall survival in the EACB group. Conclusion These data suggest that there may be distinct biological behaviors between ACB and EACB and may provide useful information to better understand the prognostic characteristics of patients with ACB and to improve outcome prediction in patients with ACB.

Prognostic factors in duodenal adenocarcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15797-e15797
Author(s):  
Brandon M Huffman ◽  
Zhaohui Jin ◽  
Cristobal T. Sanhueza ◽  
Mindy L. Hartgers ◽  
Benny Johnson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Lymph Node ◽  
Tumor Invasion ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Clinical Staging ◽  
Lymph Node Status ◽  
Duodenal Adenocarcinoma

e15797 Background: Duodenal adenocarcinoma is a rare tumor representing approximately 0.3% of all gastrointestinal tract cancers. Prognostic factors in relation to survival outcomes for these patients are sporadically reported in the medical literature. We aimed to evaluate outcomes of patients with duodenal adenocarcinoma who underwent pancreaticojejunostomy treated at Mayo Clinic Rochester from January 1, 2006 to December 31, 2016. Methods: Clinicopathological data of 52 duodenal cancer patients were collected. JMP software was used for statistical analysis. Kaplan-Meier method and log-rank tests were used for survival analysis, and multivariate cox proportional hazards model was used to evaluate the prognostic effect of pertinent clinical variables. All tests were two sided and a P value of < 0.05 was considered significant. Results: The median age at diagnosis was 65.9 years (range 39-81). The median overall survival was 51 months (95% CI 31.3-105.4) and the median progression free survival was 30.4 months with median follow up of 73.4 months. There were 3, 9, 21, and 19 patients with stage I, II, III, and IV disease, respectively. Depth of tumor invasion (p = 0.0156) and lymph node metastasis (p = 0.0441) were associated with overall survival on multivariate analysis. Advanced clinical staging influenced overall survival in univariate analysis, but lost prognostic significance in multivariate analysis. Age, gender, surgical technique, presence of metastases, tumor size, number of lymph nodes removed, location of duodenal segment involvement, and adjuvant treatment had no significant impact on overall survival. Laparoscopic approach did not influence survival but was associated with less hospital days (p = 0.0437). Conclusions: Depth of tumor invasion and lymph node status were associated with improved overall survival in patients with duodenal adenocarcinoma. Laparoscopic procedure decreased the hospital stay without affecting outcomes.

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 Prognostic significance of SDF-1 in colorectal cancer depends on CD8+ T-cell density

2020 ◽  
Author(s):  
Alexandros Lalos ◽  
Ali Tülek ◽  
Nadia Tosti ◽  
Robert Mechera ◽  
Alexander Wilhelm ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
T Cells ◽  
T Cell ◽  
Cell Density ◽  
Cd8 T Cells ◽  
Prognostic Significance ◽  
Cd8 T Cell ◽  
High Expression ◽  
Prognostic Impact

Abstract Background: Since colorectal cancer (CRC) remains one of the most common malignancies, a tremendous amount of studies keep taking place in this field. Over the past 25 years, a notable part of the scientific community has focused on the association between the immune system and colorectal cancer. A variety of studies have shown that high densities of infiltrating CD8+ T cells are associated with improved disease-free and overall survival in colorectal cancer (CRC). Stromal cell-derived factor-1 (SDF-1) is a protein that regulates leukocyte trafficking and is variably expressed in several healthy and malignant tissues. There is strong evidence that SDF-1 has a negative prognostic impact on colorectal cancer (CRC). However, based on a significant correlation of SDF-1 and CD8+ T cells in a previous study (r=0.53, p<0.0001), we hypothesized that the prognostic significance of SDF-1 in CRC could depend on the immune microenvironment. Therefore, we explored the combined prognostic significance of SDF-1 expression and CD8+ T cell density in a large CRC collective. Methods: We analyzed a tissue microarray (TMA) of 613 patient specimens of primary CRCs by immunohistochemistry (IHC) for the expression of SDF-1 by tumor cells and tumor-infiltrating immune cells (TICs) and CD8+ T-cells. Besides, we analyzed the expression of SDF-1 at the RNA level in The Cancer Genome Atlas cohort (TCGA). Results: We found that the the combined high expression of SDF-1 and CD8+ T-cell infiltration shows a favorable 5-year overall survival rate (66%; 95%CI=48–79%) compared to tumors showing a high expression of CD8+ T-cells only (55%; 95%CI=45–64%; p=0.0004). High expression of SDF-1 and CD8+ T-cells infiltration was significantly associated with a favorable prognosis also in a validation group (p=0.016). Univariate and multivariate Hazard Cox regression survival analysis considering the combination of both markers revealed that the combined high expression of SDF-1 and CD8+ T cells was an independent, favorable, prognostic marker for overall survival (HR=0.34, 95%CI=0.17–0.66; p=0.002 and HR=0.45, 95%CI=0.23–0.89; p=0.021, respectively). In a spearman’s correlation analysis from the TCGA cohort, SDF-1 also correlated significantly with CD8+ T cells (r=0.28). Conclusions: SDF-1 high /CD8 high density represents an independent, favorable, prognostic condition in CRC, most likely due to an effective antigen-specific immune response.

Prognostic factors in patients who received surgery for colorectal cancer with peritoneal metastasis.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 574-574
Author(s):  
Akinobu Furutani ◽  
Tomohiro Yamaguchi ◽  
Yusuke Kinugasa ◽  
Akio Shiomi ◽  
Hiroyasu Kagawa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Survival Rate ◽  
Distant Metastasis ◽  
Peritoneal Metastasis ◽  
Primary Tumor ◽  
Postoperative Chemotherapy ◽  
R0 Resection

574 Background: Peritoneal metastasis (PM) in patients diagnosed with colon cancer is associated with a poor prognosis. We aimed to analyze prognostic factors associated with PM in patients diagnosed with colorectal cancer (CRC). Methods: We evaluated 237 patients who underwent surgery between 2002 and 2016 for CRC with PM. The extent of PM was evaluated using the Peritoneal Cancer Index (PCI). Clinicopathological variables, PCI score, surgical curability, and the administration of postoperative chemotherapy were evaluated. Overall survival was analyzed using the Kaplan-Meier method. Multivariate analysis was performed to assess the prognostic value of these variables, using the Cox regression model. Results: Our patients included 119 men and 118 women with a median age of 64 (range: 21–90) years. The primary tumor sites were the right-sided colon (n = 103), left-sided colon (n = 84), and rectum (n = 50). The median PCI score was 4 (range: 1–30). Synchronous PM was detected at the time of diagnosis of the primary tumor in 165 patients (69.6%). Distant metastases except peritoneal metastases was detected in 137 patients (57.8%). R0 resection was performed in 62 patients (19.0%). Postoperative chemotherapy was performed in 165 patients (69.6%). The median survival time in all patients was 19.4 (range: 0–30) months, and the five-year overall survival rate was 16.3%. Multivariate analysis revealed that PCI ≤ 5 (hazard ratio [HR]: 2.56, 95% confidence interval [CI]: 1.56-4.32, P < 0.01); the absence of distant metastasis, except peritoneal metastasis (HR: 1.65, CI: 1.15-2.40, P < 0.01); R0 resection (HR: 4.21, CI: 2.44-7.50, P < 0.01) affected the survival rate. Conclusions: Our results show that a low PCI, the absence of distant metastasis except peritoneal metastasis, and R0 resection are prognostic factors in patients diagnosed with PM-CRC.

scholarly journals The Prognostic Significance of CD44V6, CDH11, andβ-Catenin Expression in Patients with Osteosarcoma

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Zhouming Deng ◽  
Guangfeng Niu ◽  
Lin Cai ◽  
Renxiong Wei ◽  
Xiaolei Zhao
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Survival Analysis ◽  
Cell Adhesion ◽  
Survival Time ◽  
Cell Adhesion Molecules ◽  
Clinical Stage ◽  
Prognostic Significance ◽  
Expression Rate ◽  
The Relationship

This study aimed to examine the expression of and the relationship between CD44V6, CDH11, andβ-catenin. The expression of these cell adhesion molecules was detected in 90 osteosarcoma and 20 osteochondroma specimens using immunohistochemistry. Associations between these parameters and clinicopathological data were also examined. The expression rates of CD44V6, CDH11, andβ-catenin were 25.0% (5/20), 70.0% (14/20), and 20.0% (4/20) in osteochondroma specimens, respectively. Compared to osteochondromas, the proportions of expression of CD44V6 andβ-catenin in osteosarcoma specimens increased to 65.6% (59/90) and 60.0% (54/90), respectively. However, the expression rate of CDH11 in osteosarcomas was reduced to 40.0% (36/90). The expression of these markers was significantly associated with metastasis and overall survival (P<0.05). Survival analysis revealed that patients with increased expression of CD44V6 andβ-catenin as well as decreased expression of CDH11 were correlated with a shorter survival time. Multivariate analysis indicated that clinical stage, metastasis status, and the expression of CD44V6, CDH11, andβ-catenin were found to be associated with overall survival. Further, the expression ofβ-catenin and that of CD44V6 were positively correlated with each other. Thus, our results indicated abnormal expression of CD44V6, CDH11, andβ-catenin in osteosarcomas and osteochondromas, which may provide important indicators for further research.

NOTCH1 as a potential prognostic biomarker for anti-VEGF therapy in patients with metastatic colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11038-11038
Author(s):  
Tadeu Ferreira Paiva ◽  
Alexandre Andre Balieiro Anastacio da Costa ◽  
Flavio Augusto Ismael Pinto ◽  
Victor Hugo Fonseca Jesus ◽  
Raul A. Marques ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Lymph Node ◽  
Liver Metastasis ◽  
Lymph Node Metastasis ◽  
Metastatic Colorectal Cancer ◽  
Response Rate ◽  
High Expression ◽  
Node Metastasis

11038 Background: There are no validated biomarkers for clinical response or survival benefit in patients treated with bevacizumab (Bv) in advanced metastatic colorectal cancer (mCRC). The aim of this study was to evaluate the predictive value of putative biomarkers in mCRC. Methods: One hundred and five mCRC patients who received Bv combined with FOLFOX or FOLFIRI were retrospectively evaluated for clinical and pathological characteristics. VEGFR1, VEGFR2, VEGFR3, PlGF, DLL4 and NOTCH1 expression were assessed by immunohistochemistry on formalin-fixed, paraffin-embedded neoplastic tissue of either primary or metastatic tissue in a tissue microarray. High levels of expression were defined as less than or equal to or more than the median. Survival curves were calculated by the Kaplan-Meier method and compared by the log-rank test. For multivariate analysis the Cox proportional hazards model was used. Results: Grade 1 or 2 (p=0.01), non-mucin-producing histology (p=0.04) and presence of liver metastasis (p=0.001) were associated with a higher response rate. There was no difference between the expression of markers and the response rate. ECOG 0 or 1 (p=0.002), grade 1 or 2 (p=0.02), liver metastasis (p=0.003), no lymph node metastasis (p=0.01) no peritoneal metastasis (p=0.02) and resection of metastasis (p<0.001) were correlated with higher progression-free survival (PFS). There was also a strong correlation between ECOG 0 or 1 (p=0.001), grade 1 or 2 (p=0.006), no lymph node metastasis (p=0.004), liver metastasis (p<0.001) and resection of metastasis (p<0.0001) with better overall survival. There was a trend between high expression of NOTCH1 (p=0.06) and worst PFS.High expression of VEGFR2 (p=0.07) was slightly associated with a better overall survival, while high expression of NOTCH1 was associated with a worse overall survival (p=0.01). Using multivariate analysis, NOTCH1 proved to be an independent variable for adverse overall survival (HR 2.01, IC 1.07 – 3.77, p=0.02). Conclusions: High NOTCH1 expression assessed by immunohistochemistry is capable of predicting poor survival in advanced colorectal cancer patients treated with bevacizumab.

scholarly journals Prognostic Factors of Radiofrequency Ablation plus Systemic Chemotherapy for Unresectable Colorectal Cancer with Liver Metastasis

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Ky Thai Doan ◽  
Long Nguyễn Việt ◽  
Thinh Nguyen Tien ◽  
Binh Nguyen Canh ◽  
Hoai Ngo Thi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Radiofrequency Ablation ◽  
Liver Metastasis ◽  
Systemic Chemotherapy ◽  
Univariate Analysis ◽  
Survival Rates ◽  
Liver Lesions

Introduction. Survival outcomes in patients with unresectable colorectal cancer (CRC) liver metastasis treated by radiofrequency ablation (RFA) combined with systemic chemotherapy and correlation with potential prognostic factors were investigated. Material and Methods. A retrospective cohort study was conducted on 61 CRC patients with unresectable liver metastasis who underwent liver tumor-directed percutaneous RFA combined with conventional systemic chemotherapy between October 2013 and September 2018. Survival analyses were conducted using the Kaplan-Meier method, and the log-rank test was used to characterize differences in the median survival time and the 1-year, 3-year, and 5-year overall survival rates of subgroups to identify prognostic factors. Results. Median overall survival and progression-free survival of all patients were 32 and 14 months, respectively. The cumulative survival rates at 1-, 3-, and 5-years were 93.2%; 44.5%, and 38.2%, respectively. Univariate analysis revealed that pre-RFA serum CEA levels, Eastern Cooperative Oncology Group (ECOG) status, number of liver lesions, the size of the largest lesion, and the total lesion size were prognostic factors. However, multivariate analysis demonstrated that only the number of liver lesions and the size of the largest lesion were independent prognostic factors for survival. Conclusion. RFA plus systemic chemotherapy provides an encouraging survival outcome for patients with unresectable CRC liver metastasis. Multivariate analysis demonstrated that the number and size of liver metastatic lesions are independent prognostic factors for survival.

scholarly journals Diagnostic and prognostic value of the methylation status of secreted frizzled-related protein 2 in colorectal cancer

2011 ◽  
Vol 34 (1) ◽  
pp. 88 ◽  
Author(s):  
Dong Tang ◽  
Jun Liu ◽  
Dao-rong Wang ◽  
Hai-feng Yu ◽  
Yong-kun Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Promoter Methylation ◽  
Cox Regression ◽  
Precancerous Lesions ◽  
Methylation Status ◽  
Prognostic Significance ◽  
Related Protein ◽  
Serum Samples ◽  
Cox Regression Analysis

Purpose: The aim of this study was to investigate the diagnostic and prognostic significance of the methylation status of secreted frizzled-related protein 2 (SFRP2) in colorectal cancer (CRC). Methods: Methylation-specific PCR assay was performed to analyze SFRP2 promoter methylation in solid tissue, stool and serum samples collected from 169 CRC patients, 63 patients with advanced adenomas, 46 patients with non-adenomatous polyps and 30 normal healthy controls. Results: Methylated SFRP2 was frequently detected in CRC tissues and precancerous lesions. The sensitivity of SFRP2 methylation levels in tissue, fecal and serum DNA for the detection of CRC was similar, ranging from 66.9 to 88.2%; however, serum SFRP2 methylation levels showed a markedly higher specificity in discriminating CRCs from benign adenomas than those of SFRP2 methylation levels in tumor and fecal DNA. Moreover, serum SFRP2 methylation was significantly associated with poor differentiation grade (P=0.019), serosal/subserosal invasion (P < 0.001), lymph node metastasis status (P < 0.001) and TNM stage (P < 0.001) of CRC. CRC patients with SFRP2 hypermethylation in tumor, stool and serum samples had a significantly shorter overall survival than those negative for SFRP2 methylation (P=0.0216, 0.0219, and 0.0255, respectively). Multivariate Cox regression analysis revealed that SFRP2 promoter methylation in tumor samples was an independent prognostic factor for overall survival. Conclusion: Our data suggest that serum SFRP2 methylation status represents a promising, non-invasive marker for CRC detection and staging. Hypermethylated SFRP2 may have prognostic relevance in patients with CRC.

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