Prognostic significance of p53 expression in malignant bone tumors: a meta-analysis

Osteosarcoma and Ewing’s sarcoma are the two most common primary malignant bone tumors, and findings of prognostic factors are important for clinicians to decide treatment options. High p53 expression has been implicated in tumor development and progression, but studies investigating the prognostic role of p53 overexpression in malignant bone tumors report conflicting findings. We performed a meta-analysis to assess the relationship between p53 overexpression and the survival of malignant bone tumors. A meta-analysis of 13 studies with a total of 703 patients was carried out to evaluate the association between p53 overexpression and overall survival (OS) and disease-free survival (DFS) in patients with malignant bone tumors. The pooled hazard ratio (HR) with its 95 % confidence interval (CI) was used as the effect size estimate. There was no between-study heterogeneity in both OS studies (I ²?=?0.0 %) and DFS studies (I ²?=?0.0 %). Overall, high p53 expression predicted both poor OS (HR 2.13, 95 % CI 1.81–2.52, P?<?0.001) and poor DFS (HR 2.06, 95 % CI 1.58–2.69, P?<?0.001) in patients with malignant bone tumors. Subgroup analyses by tumor types suggested that p53 expression predicted poor OS in both osteosarcoma patients (HR 2.15, 95 % CI 1.78–2.60, I ²?=?15.2 %, P?<?0.001) and Ewing’s sarcoma patients (HR 2.09, 95 % CI 1.47–2.97, I ²?=?0.0 %, P?<?0.001). Besides, p53 expression also predicted poor DFS in both osteosarcoma patients (HR 2.38, 95 % CI 1.60–3.52, I ²?=?0.0 %, P?<?0.001) and Ewing’s sarcoma patients (HR 1.83, 95 % CI 1.28–2.63, I ²?=?0.0 %, P?=?0.001). Egger’s test also did not suggest evidence for publication bias in both OS studies (P?=?0.615) and DFS studies (P?=?0.258). High p53 expression indicates a poorer prognosis for patients with osteosarcoma and Ewing’s sarcoma.     

BCL6 is a negative prognostic factor and exhibits pro-oncogenic activity in ovarian cancer

Background: Dysregulation of BCL6 plays critical oncogenic roles and facilitates tumorigenesis in various malignancies. However, whether the aberrant expression of BCL6 in ovarian carcinoma is associated with malignancy, metastasis or prognosis remains unknown. Our study aimed to investigate the expression of BCL6 in ovarian carcinoma and its possible correlation with clinicopathological features as well as patient survival to reveal its biological effects in ovarian tumor progression. Methods: Immunochemistry analysis was performed in 105 cases of ovarian carcinoma covering the histological types of serous, endometrioid and clear cell. Spearman analysis was used to calculate the correlation between pathological parameters and the expression of BCL6. Kaplan–Meier method and Cox proportional hazards analysis were used to analyze the disease-specific survival (DSS) and disease-free survival (DFS). We also assessed whether overexpression and knockdown of BCL6 influence in vitro cell proliferation, cell cycle progression, as well as tumor cell invasion and migration. Results: The expression of BCL6 was higher in all three major kinds of ovarian cancer in comparison with paratumorous epithelium. BCL6 expression was tightly correlated with FIGO staging, lymph node metastasis and recurrence. Higher expression of BCL6 led to a significantly poorer DSS and DFS and multivariate analysis revealed that BCL6 was an independent risk factor of DSS and DFS. Enforced overexpression of BCL6 in ovarian tumor cells stimulated proliferation by inducing G₁–S transition, and promoted tumor cell invasion and migration. Conversely, RNA interference–mediated silencing BCL6 expression inhibited proliferation by altered cell cycle progression and reduced the ability of the cells to migrate, and invade the extracellular matrix in culture. Conclusions: Our study suggests that the inappropriate activation of BCL6 predicts poor prognosis and promotes tumor progression in ovarian carcinoma. Targeting BCL6 could be a novel therapeutic choice for treating ovarian carcinoma patients.     

Role of stratifin (14-3-3 sigma) in adenocarcinoma of gallbladder: A novel prognostic biomarker

BackgroundGallbladder cancer (GBC) is a rare and fatal biliary tract malignancy. Genetic derangements are one of many factors that determine the prognosis of GBC. In this study, the expression of the stratifin (SFN) gene encoding 14-3-3 sigma protein, which is reported to be associated with the metastatic property of cholangiocarcinoma cells, was investigated in GBC.Material and methodsFormalin-fixed paraffin-embedded cancer (n = 37) and non-cancer control tissues (n = 14) of gallbladders from patients who underwent surgical resection from January 2006 to May 2015 were retrieved. The expression of SFN normalized with that of ACTB was determined using RT-qPCR. Multivariate analysis of factors affecting disease-free survival (DFS) and overall survival (OS) including the type of SFN expression was performed.ResultThe average expression level of SFN in cancer was higher than that in control tissues (p = 0.002). The relative SFN expression in cancer tissue was classified as overexpression (n = 14) and control level expression (n = 23) according to the receiver operating characteristic (ROC) curves for discriminating early GBC recurrence or metastasis after surgery. The SFN overexpression group was associated with lower rates of distant metastasis and early tumor recurrence following resection. The univariate analysis demonstrated factors affecting DFS, including resection margin (p < 0.001), lymphovascular invasion (p = 0.040), perineural invasion (p = 0.046), and SFN expression (p < 0.001). The multivariate analysis revealed that the resection margin (p = 0.019) and SFN expression (P = 0.040) were independent prognostic factors of DFS.ConclusionTo achieve the longest survival, margin-free resection is recommended. The overexpression of SFN in GBC is associated with better prognosis, lower rates of early cancer recurrence, and distant metastasis following resection. SFN expression might be a novel prognostic biomarker in GBC treatment. Further studies to elucidate the role of SFN might unveil its clinical benefit in cancer treatment regimens.     

Detection and clinical significance of genes in primary gastrointestinal MALT lymphoma

In clinical practice, we found that some primary gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma had different prognosis. This study aimed to explore the role of IGH rearrangement, p53 and ATM gene variations in the assessment of prognosis in primary gastrointestinal MALT lymphoma. In 50 cases of primary gastrointestinal MALT lymphoma (1) IGH arrangement was found in 59.5 % of patients with primary gastrointestinal MALT lymphoma; IGH arrangement was found in 48.4 % of patients with primary gastrointestinal MALT lymphoma at stage I–II and in 90.9 % of patients at stage III–IV (χ ²?=?6.093, p?<?0.05). Average survival time in patients with IGH rearrangement was 16.39 months, being shorter than that in patients with non-IGH rearrangement (38.13 months) (t?=?3.239, p?<?0.01). (2) p53 gene deletion was found in 31.0 % of patients with primary gastrointestinal MALT lymphoma; p53 gene deletion was found in 22.6 % of patients with primary gastrointestinal MALT lymphoma at stage I–II and in 54.5 % of patients at stage III–IV (χ ²?=?3.882, p?<?0.05). Average survival time in patients with p53 gene deletion was 8.0 months, being shorter than that of patients with normal p53 gene (32.81 months) (t?=?3.609, p?<?0.01). (3) ATM gene deletion was found in 23.8 % of patients with primary gastrointestinal MALT lymphoma; ATM gene deletion was found in 16.1 % of patients with primary gastrointestinal MALT lymphoma at stage I–II and in 45.5 % of patients at stage III–IV (χ ²?=?3.849, p?<?0.05). Average survival time in patients with ATM gene deletion was 6.10 months, which is shorter than that of patients with normal ATM gene (31.71 months) (t?=?3.503, p?<?0.01). (4) IGH rearrangement, p53 and ATM gene deletion were no correlation with tumor location. (5) Average survival time in primary gastrointestinal MALT lymphoma patients of non-gene or single gene change was 33.42 months, which is longer than that of patients with multiple genes change (6.67 months) (t?=?4.013,p?<?0.01). There was a high incidence of IGH rearrangement or p53 and ATM gene deletion in patients at stage III–IV. The average survival time was shorter in these patients. Average survival time in primary gastrointestinal MALT lymphoma patients with multiple genes abnormalities was shorter than that in non-gene or single gene change patients. IGH rearrangement, p53 and ATM gene deletion may play a synergistic role in the occurrence and development of the primary gastrointestinal MALT lymphoma. Patients with multiple genes abnormalities had poor prognosis, and they should be advised early united chemotherapy.     

Elevated expression of iASPP in head and neck squamous cell carcinoma and its clinical significance

iASPP is shown to be elevated in several cancers. However, the role of iASPP in head and neck squamous cell carcinoma (HNSCC) remains unknown. We have investigated iASPP expression in HNSCC tissue and cell lines and evaluated its prognostic significance in HNSCC. The expression of iASPP in 109 primary HNSCC tissue specimens was examined by immunohistochemistry and its association with clinicopathological parameters and prognosis was analyzed. Additionally, expression status of iASPP in 16 paired HNSCC tissues and 7 HNSCC cell lines was evaluated by quantitative real-time PCR (qPCR) and immunoblotting. The protein and mRNA expression of iASPP were increased in HNSCC tissues and cell lines. Immunohistochemical staining indicated iASPP was detected in both cytoplasm and nucleus. Importantly, overexpression of cytoplasmic and nuclear iASPP was significantly associated with T classification (p?=?0.002 and p?=?0.033, respectively), clinical stage (p?<?0.001 and p?=?0.004), lymph node metastasis (p?=?0.001 and p?<?0.001), and recurrence (both p?<?0.001). Survival analysis demonstrated high iASPP expression significantly correlated with shorter disease-free survival (DFS) (both p?<?0.001 for cytoplasmic and nuclear expression) and overall survival (OS) (both p?<?0.001 for cytoplasmic and nuclear expression). Multivariate analysis revealed that cytoplasmic iASPP was the only independent prognostic factor for HNSCC patients. iASPP expression is elevated in HNSCC tissues and cell lines, which suggests iASPP may contribute to the malignant progression of HNSCC, and serves as a novel prognostic marker and a potential therapeutic target in HNSCC.     

Correlation of TNFAIP8 overexpression with the proliferation,metastasis, and disease-free survival in endometrial cancer

Tumor necrosis factor alpha-induced protein 8 (TNFAIP8) is an apoptosis regulator proven to have an important function in the proliferation, invasion, metastasis, and progression of malignancies. In this study, we investigated the clinical role of TNFAIP8 overexpression in endometrial cancer (EC) and determined the relationship of TNFAIP8 with the proliferative antigen Ki-67 and metastasis-related gene matrix metallopeptidase 9 (MMP9) in 225 tumor specimens by immunohistochemistry and western blot, in order to elucidate more information on the role of TNFAIP8 protein with regard to the pathogenesis of EC. An association was observed between TNFAIP8 overexpression and clinicopathologic factors, such as advanced International Federation of Gynecology and Obstetrics stage (P?<?0.001), higher histologic grade (P?=?0.017), deep myometrial invasion (P?=?0.030), lymphovascular space invasion (P?=?0.011), lymph node metastasis (P?<?0.001), and recurrence. Furthermore, TNFAIP8 overexpression was strongly correlated with MMP9 and Ki-67 expression in the progression of ECs. Patients with high expression of TNFAIP8 (P?<?0.001 for both) and Ki-67 (P?=?0.007 and P?=?0.008) had poor overall survival and disease-free survival (DFS) rates. MMP9 overexpression did not affect survival outcomes (P?>?0.05). Multivariate Cox regression analysis revealed that TNFAIP8 (P?=?0.029) and lymph node metastasis (P?=?0.022) were independent factors of DFS in patients with EC. These findings suggested that TNFAIP8 may be used as a prognostic marker for the recurrence of EC, and its promotion of the proliferation and metastasis in EC may be due to its mediation of Ki-67 and MMP9.     

Clinicopathological factors influencing the outcomes of surgical treatment in patients with T4a hypopharyngeal cancer

Background

The purpose of this study was to determine prognostic factors influencing outcomes of surgical treatment in patients with T4a hypopharyngeal cancer.

Methods

The present study enrolled 93 patients diagnosed with T4a hypopharyngeal cancer who underwent primary surgery between January 2005 and December 2015 at six medical centers in Korea. Primary tumor sites included pyriform sinus in 71 patients, posterior pharyngeal wall in 14 patients, and postcricoid region in 8 patients. Seventy-two patients received postoperative radio(chemo)therapy.

Results

Five-year disease-free survival (DFS) and disease-specific survival (DSS) rates were 38% and 45%, respectively. In univariate analysis, 5-year DFS was found to have significant and positive correlations with margin involvement (p?<?0.001) and extracapsular spread (p?=?0.025). Multivariate analysis confirmed that margin involvement (hazard ratio (HR): 2.81; 95% confidence interval (CI): 1.49-5.30; p?=?0.001) and extracapsular spread (HR: 2.08; 95% CI: 1.08-3.99; p?=?0.028) were significant factors associated with 5-year DFS. In univariate analysis, cervical lymph node metastasis (p?=?0.048), lymphovascular invasion (p?=?0.041), extracapsular spread (p?=?0.015), and esophageal invasion (p?=?0.033) were significant factors associated with 5-year DSS. In multivariate analysis, extracapsular spread (HR: 2.98; 95% CI: 1.39-6.42; p?=?0.005) and esophageal invasion (HR: 2.87; 95% CI: 1.38-5.98; p?=?0.005) remained significant factors associated with 5-year DSS.

Conclusion

Margin involvement and extracapsular spread are factors influencing recurrence while extracapsular spread and esophageal invasion are factors affecting survival in patients with T4a hypopharyngeal cancer treated by primary surgery.

     

Rsf-1 overexpression serves as a prognostic marker in human hepatocellular carcinoma

Rsf-1 (HBXAP) was recently reported to be overexpressed in various cancers and associated with the malignant behavior of cancer cells. However, the expression of Rsf-1 and its clinical significance in human hepatocellular carcinoma (HCC) have not been reported. In the present study, we analyzed the expression pattern of Rsf-1 in human HCC tissues and found that Rsf-1 was overexpressed in 41.1 % of HCC specimens. There was a significant association between Rsf-1 overexpression and tumor stage (p?=?0.0322), AFP (p?=?0.0184), and tumor relapse (p?=?0.0112). Furthermore, Rsf-1 overexpression correlated with poor overall survival in HCC patients (p?p?=?0.0079). Small interfering RNA (siRNA) knockdown in SK-Hep-1 cells with high endogenous Rsf-1 expression inhibited cell proliferation and colony formation, with downregulation of cyclin E protein. In conclusion, Rsf-1 is overexpressed in HCCs and serves as a novel tumor marker. Rsf-1 contributes to hepatocellular carcinoma cell growth through regulation of cell cycle proteins.     

The expression of glutamine-metabolism-related proteins in breast phyllodes tumors

The aim of this study was to investigate the expression of glutamine-metabolism-related proteins according to the histologic grade of phyllodes tumors (PTs) and to assess its clinical implication. We generated tissue microarrays of 224 PTs and performed immunohistochemical staining and western blot analysis of glutamine-metabolism-related molecules, including GLS1, GDH, and ASCT2. The associations between immunohistochemical results and clinicopathologic parameters were evaluated. The expression of GLS1 (p?<?0.001), GDH (p?<?0.001), and ASCT2 (p?=?0.005) in stromal components significantly increased with worsening PT histological grade. GDH expression in epithelial components significantly increased in high-grade PT (p?=?0.026). In western blot, stromal expression of GLS1, GDH, and ASCT2 increased as histologic grade increased. By univariate analysis, stromal GLS1 expression (p?=?0.022) and stromal GDH expression (p?=?0.009) were independent predictors of shorter DFS. Stromal GLS1 expression (p?<?0.001) and stromal GDH expression (p?<?0.001) were independent predictors of shorter OS. This study demonstrated that the stromal expression of the glutamine-metabolism-related proteins GLS1, GDH, ASCT2 increases with worsening histological PT grade.     

Dysregulated CXCR4 expression promotes lymphoma cell survival and independently predicts disease progression in germinal center B-cell-like diffuse large B-cell lymphoma

Abnormal expression of the chemokine receptor CXCR4 plays an essential role in tumor cell dissemination and disease progression. However, the significance of CXCR4 overexpression in de novo diffuse large B cell lymphoma (DLBCL) is unknown. In 743 patients with de novo diffuse large B cell lymphoma (DLBCL) who received standard Rituximab-CHOP immunochemotherapy, we assessed the expression of CXCR4 and dissected its prognostic significance in various DLBCL subsets. Our results showed that CXCR4⁺ patients was associated with male, bulky tumor, high Ki-67 index, activated B-cell-like (ABC) subtype, and Myc, Bcl-2 or p53 overexpression. Moreover, CXCR4⁺ was an independent factor predicting poorer progression-free survival in germinal-center B-cell-like (GCB)-DLBCL, but not in ABC-DLBCL; and in patients with an IPI of ≤2, but not in those with an IPI>2. The lack of prognostic significance of CXCR4 in ABC-DLBCL was likely due to the activation of p53 tumor suppressor attenuating CXCR4 signaling. Furthermore, concurrent CXCR4⁺ and BCL2 translocation showed dismal outcomes resembling but independent of MYC/BCL2 double-hit DLBCL. Gene expression profiling suggested that alterations in the tumor microenvironment and immune responses, increased tumor proliferation and survival, and the dissemination of CXCR4⁺ tumor cells to distant organs or tissues were underlying molecular mechanisms responsible for the CXCR4⁺ associated poor prognosis.     

Clinical significance of Ki-67 and p53 expression in curatively resected non-small cell lung cancer

The aim of this study is to explore the association of Ki-67 and p53 expression with prognosis in non-small cell lung cancer (NSCLC) patients who underwent curative resection. We retrospectively identified 116 consecutive patients with stages I–III NSCLC who underwent curative resection at a single center from January 2007 to December 2012. Ki-67 and p53 expression was assessed by immunohistochemistry. Data on clinicopathologic features and survival were collected retrospectively. Ki-67 expression in 109 samples and p53 expression in 115 patients were analyzed. According to the results, 108 patients (99 %) showed at least some expression of Ki-67. The median Ki-67 expression level was 30 %. Positive p53 expression was observed in 91 (79 %) patients. Higher Ki-67 expression (>40 %) was significantly more frequent in male (26 vs. 4 % in female, p?=?0.002), ever-smoker (31 vs. 10 % in never-smoker, p?=?0.024), and non-adenocarcinoma (30 vs. 11 % of adenocarcinoma, p?=?0.012) patients. In univariable analysis, median disease-free survival (DFS) was shorter with higher Ki-67 expression (16.1 vs. 61.9 months in those with lower Ki-67 expression, p?=?0.005), and p53 expression did not show an association with DFS. Among 42 patients with stage I NSCLC who did not receive adjuvant chemotherapy, DFS was significantly worse in patients with higher Ki-67 expression (2-year DFS rate 57 vs. 88 %, p?=?0.018). In a Cox regression model, higher Ki-67 expression (>40 %) was a significant independent prognostic factor associated with poorer DFS (HR 2.9, 95 % CI 1.3–6.2) along with TNM stage and age. Higher Ki-67 expression (>40 %) showed an independent association with shorter DFS in NSCLC patients who underwent curative resection.     

Lipoprotein Receptor Associated Protein (LRPAP1) Insertion/Deletion Polymorphism: Association with Gallbladder Cancer Susceptibility

Background

Low-density lipoprotein receptor-related protein associated protein (LRPAP1) insertion/deletion polymorphism influences cholesterol homeostasis and may confer risk for gallstone disease and gallbladder carcinoma (GBC) incidence usually parallels with the prevalence of cholelithiosis.

Aim

We aimed to examine the role of LRPAP1 polymorphism in susceptibility to GBC.

Methods

Present case control study included 129 proven GBC patients, 183 gallstone patients, and 208 healthy controls. Genotyping was done by polymerase chain reaction–restriction fragment length polymorphism method.

Results

The D allele of LRPAP1 was significantly higher in GBC patients as compared to gallstone patients (p?=?0.013; OR?=?1.6, 95% CI?=?1.1–2.4). However, II genotype and I allele was associated with reduced risk of GBC as compared to gallstone patients (p?=?0.002; OR?=?0.1, 95% CI?=?0.1–0.6; p?=?0.013; OR?=?0.6, 95% CI?=?0.4–0.8) The increased risk due to D allele was limited to female GBC patients (p?=?0.021; OR?=?1.8, 95% CI?=?1.1–3.0). However, reduced risk due to II genotype and I allele was observed which was also confined to female GBC patients (p?=?0.005; OR?=?0.1, 95% CI?=?0.1–0.6; p?=?0.021; OR?=?0.5, 95% CI?=?0.3–0.8). On comparing GBC patients having gallstone with gallstone patients, high risk was observed in the GBC patients having gallstone due to the presence of D allele (p?=?0.032; OR?=?1.7, 95% CI?=?1.0–2.8). However, low risk was observed because of I allele in GBC patients with gallstone in comparison to gallstone patients (p?=?0.032, OR?=?0.6, 95% CI?=?0.4–0.9).

Conclusion

It appears that ‘D’ allele may modulate the susceptibility of GBC, and the risk is independent to genetic risk of gallstone.     

Overexpression of SPAG9 correlates with poor prognosis and tumor progression in hepatocellular carcinoma

Sperm-associated antigen 9 (SPAG9) was reported as a novel biomarker for several cancers and associated with the malignant behavior of cancer cells. However, its expression pattern and biological role in human hepatocellular carcinoma (HCC) have not been reported. In the present study, we analyzed SPAG9 expression in human HCC tissues by immunohistochemistry and found that SPAG9 overexpression is correlated with tumor stage (p?p?=?0.019), tumor size (p?=?0.034), AFP levels (p?=?0.006), and tumor relapse (p?=?0.0017). Furthermore, SPAG9 overexpression is correlated with poor overall survival (p?p?=?0.002). Transfection of SPAG9 small interfering RNA (siRNA) was performed in Bel-7402 cell line. Colony formation and MTT showed that SPAG9 siRNA knockdown inhibited HCC cell proliferation. We also found that SPAG9 depletion could increase cell apoptosis. In addition, the level of cyclin D1 and cyclin E protein expression was downregulated after siRNA treatment. In conclusion, SPAG9 is overexpressed in human HCC and serves as a prognostic marker. SPAG9 contributes to cancer cell growth through regulation of cyclin proteins.     

Association of genetic variants of xenobiotic and estrogen metabolism pathway (CYP1A1 and CYP1B1) with gallbladder cancer susceptibility

Gallbladder carcinoma is a highly aggressive cancer with female predominance. Interindividual differences in the effectiveness of the activation/detoxification of environmental carcinogens and endogenous estrogens may play a crucial role in cancer susceptibility. The present study included 410 patients with carcinoma of the gallbladder (GBC) and 230 healthy subjects. This study examined association of CYP1A1-MspI, CYP1A1-Ile462Val, and CYP1B1-Val432Leu with GBC susceptibility. CYP1A1-MspI [CC] and CYP1A1-Ile462Val [iso/val] genotypes were found to be significantly associated with GBC (p?=?0.006 and p?=?0.03, respectively), as compared to healthy controls, while CYP1B1-Val432Leu was not associated with GBC. The CYP1A1 haplotype [C-val] showed a significant association with GBC (p?=?0.006). On stratification based on gender, the CYP1A1-MspI [CC] genotype showed an increased risk of GBC in females (p?=?0.018). In case-only analysis, tobacco users with CYP1A1-MspI [CT] genotypes were at a higher risk of GBC (p?=?0.008). Subdividing the GBC patients on the basis of gallstone status, the CYP1A1 haplotype [C-val] imparted a higher risk in patients without stones when compared to controls (p?=?0.001). The results remained significant even after applying Bonferroni correction. Multivariate analysis revealed an increased risk of CYP1A1 iso/val and val/val genotypes in GBC patients having BMI >25 (p?=?0.021). The CYP1A1 polymorphisms may confer increased risk of GBC, probably due to impaired xenobiotic or hormone metabolism through a gallstone-independent pathway.     

Clinical significance of serum ADP-ribosylation and NAD glycohydrolase activity in patients with colorectal cancer

The objective of this study was to evaluate the clinical significance of serum ADP-ribosylation and NAD glycohydrolase activity in patients with colorectal cancer (CRC). A total of 108 patients with CRC who underwent curative surgery and 20 healthy volunteers were enrolled in this study. ADP-ribosylation and NAD glycohydrolase activity levels were determined. The association of ADP-ribosylation and NAD glycohydrolase with clinical and laboratory factors and their impact on overall survival (OS) and disease free survival (DFS) were shown. The preoperative ADP-ribosylation and NAD glycohydrolase activity levels were significantly higher in patients with CRC than in the control group (p?<?0.001). ADP-ribosylation and NAD glycohydrolase activity levels were correlated with tumor stage (p?=?0.05, p?=?0.001), stage of disease (p?<?0.001, p?<?0.001), serum CEA level (p?<?0.001, p?<?0.001), and site of lesion (p?<?0.001, p?<?0.001), respectively. Patients with high ADP-ribosylation had significantly unfavorable OS and DFS compared with those with lower levels (p?<?0.001, p?<?0.001), respectively. Moreover, the patients with high NAD glycohydrolase activity showed significantly worse OS and DFS rates, similar to ADP-ribosylation. Serum levels of ADP-ribosylation and NAD glycohydrolase activity correlate well with tumor stage, stage of disease, serum CEA level, and site of lesion. In conclusion, elevated levels of preoperative ADP-ribosylation and NAD glycohydrolase levels in serum are associated with poor prognosis in patients with CRC.