scholarly journals Preoperative Serum Interleukin-6 Is a Potential Prognostic Factor for Colorectal Cancer, including Stage II Patients

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Kazuyoshi Shiga ◽  
Masayasu Hara ◽  
Takaya Nagasaki ◽  
Takafumi Sato ◽  
Hiroki Takahashi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Interleukin 6 ◽  
Prognostic Significance ◽  
Significant Risk ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Disease Stage ◽  
Healthy Controls ◽  
Preoperative Serum ◽  
The Mean

Aims. To evaluate the prognostic significance of serum interleukin-6 (IL-6) in colorectal cancer (CRC).Patients and Methods. Preoperative serum IL-6 was measured in 233 CRC patients and 13 healthy controls. Relationships between IL-6 and various clinicopathological factors were evaluated, and the overall survival (OS) and disease-free survival (DFS) rates according to IL-6 status were calculated for all patients and according to disease stage.Results. The mean IL-6 level was 6.6 pg/mL in CRC patients and 2.6 pg/mL in healthy controls. Using a cutoff of 6.3 pg/mL, obtained using receiver operating characteristic curve analysis, 57 patients had a high IL-6 level. The mean value was higher for stage II disease than for stage III disease. IL-6 status correlated with C-reactive protein (CRP) and carcinoembryonic antigen levels, obstruction, and pT4 disease. The OS differed according to the IL-6 status for all patients, whereas the DFS differed for all patients and for those with stage II disease. The Cox proportional hazards model showed that pT4 disease was an independent risk factor for recurrence in all CRC patients; IL-6, CRP, and pT4 were significant risk factors in stage II patients.Conclusions. The preoperative IL-6 level influences the risk of CRC recurrence.

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.

scholarly journals Prognostic significance of MUC2, CDX2 and SOX2 in stage II colorectal cancer patients

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sara Ribeirinho-Soares ◽  
Diana Pádua ◽  
Ana Luísa Amaral ◽  
Elvia Valentini ◽  
Daniela Azevedo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Prognostic Significance ◽  
Tumor Resection ◽  
Disease Free Survival ◽  
Predictive Biomarkers ◽  
Stage Ii ◽  
Health Concern ◽  
Rank Test ◽  
Low Expression

Abstract Background Colorectal cancer (CRC) remains a serious health concern worldwide. Despite advances in diagnosis and treatment, about 15 to 30% of stage II CRC patients subjected to tumor resection with curative intent, develop disease relapse. Moreover, the therapeutic strategy adopted after surgery is not consensual for these patients. This supports the imperative need to find new prognostic and predictive biomarkers for stage II CRC. Methods For this purpose, we used a one-hospital series of 227 stage II CRC patient samples to assess the biomarker potential of the immunohistochemical expression of MUC2 mucin and CDX2 and SOX2 transcription factors. The Kaplan-Meier method was used to generate disease-free survival curves that were compared using the log-rank test, in order to determine prognosis of cases with different expression of these proteins, different mismatch repair (MMR) status and administration or not of adjuvant chemotherapy. Results In this stage II CRC series, none of the studied biomarkers showed prognostic value for patient outcome. However low expression of MUC2, in cases with high expression of CDX2, absence of SOX2 or MMR-proficiency, conferred a significantly worst prognosis. Moreover, cases with low expression of MUC2 showed a significantly clear benefit from treatment with adjuvant chemotherapy. Conclusion In conclusion, we observe that patients with stage II CRC with low expression of MUC2 in the tumor respond better when treated with adjuvant chemotherapy. This observation supports that MUC2 is involved in resistance to fluorouracil-based adjuvant chemotherapy and might be a promising future predictive biomarker in stage II CRC patients.

Correlation of plasma TIMP-1 levels and disease-free survival in primary colorectal cancer independent of serum CEA levels

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22040-e22040
Author(s):  
H. J. Nielsen ◽  
N. Brünner ◽  
I. J. Christensen
Keyword(s):  
Colorectal Cancer ◽  
Local Recurrence ◽  
Prognostic Markers ◽  
Disease Free Survival ◽  
Distant Metastases ◽  
Disease Stage ◽  
Free Survival ◽  
Preoperative Serum ◽  
Serum Cea ◽  
Disease Free

e22040 Background: Introduction of independent prognostic markers may play a significant role in future treatment of early stage colorectal cancer (CRC). CEA is still the only recommended (ASCO and EGTM) serological marker in CRC. However, Tissue Inhibitor of Metallo Proteinases-1 (TIMP-1), which is a glycoprotein that acts as an inhibitor of most of the active matrix metalloproteinases, has previously been shown to carry independent prognostic information in patients with primary CRC. The purpose of the present study was to assess the combination of preoperative serum CEA and plasma TIMP-1as prognostic markers in patients undergoing resection for primary CRC. Methods: In the present prospective study serum and plasma samples were collected before surgery from 422 patients with primary CRC stage I-III. CEA was determined in serum by a commercial assay and TIMP-1 was determined in plasma using a thoroughly validated, in-house ELISA. Time to recurrence or death of CRC was registered and the association to serum CEA and plasma TIMP-1 levels were studied in a Cox multivariate model including age, gender, disease stage and tumor location. Hazard ratios and 95% confidence intervals (HR (95%CI)) for disease free survival (DFS) were calculated. Results: An event was recorded in 186 patients, 75 had local recurrence, 103 had a distant metastases (28 of these patients had both local recurrence and distant metastases) and 36 died from their cancer without a registered recurrence. Scoring CEA and TIMP-1 as continuous variables on a logarithmic scale (base 2), both serum CEA and plasma TIMP-1 were statistically significant in a multivariable analysis with HR=1.12 (1.03–1.21) and HR=1.51 (1.12–2.04), respectively. Additional calculations of low CEA plus low TIMP-1, high CEA plus low TIMP-1, low CEA plus high TIMP-1 and high CEA plus high TIMP-1 showed that high plasma TIMP-1 levels carried prominent information of poor prognosis independent of CEA. Conclusions: Preoperative serum CEA and plasma TIMP-1 levels were independent predictors of disease free survival for patients with primary CRC. Combination of the two proteins showed that TIMP-1 was a prominent predictor of poor DFS independent of CEA. [Table: see text]

Prognostic significance of pathological biomarkers in patients with stage II-III colorectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14518-14518
Author(s):  
C. Funaioli ◽  
C. Pinto ◽  
C. Ceccarelli ◽  
F. Di Fabio ◽  
D. Cuicchi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Primary Tumor ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Stage Ii ◽  
Stage Iii ◽  
Disease Stage ◽  
Primary Tumor Site ◽  
The Impact

14518 Background: Biopathological colorectal cancer (CRC) studies have provided information on pathogenesis, but it is unclear how important biomarkers actually are in predicting prognosis. The aim of our study was to define the prognostic significance of biomarkers and a biopathological profile that could predict an increase in the disease relapse risk in stage II-III CRC patients (pts). Methods: The primary tumor of the CRC pts treated with surgery was immunohistochemically evaluated on the Ki67, p53, bcl-2, TS, EGFR, MLH1 and MSH2 expressions. All 7 markers were measured using standard immunohistochemical techniques. The biomarker evaluations were scored by just one pathologist. Results: Between March 2001 and October 2006 the primary tumor of 242 consecutive pts was investigated. Pt characteristics were: males 141(58.3%), females 101(41.7%); median age 68.5 (24–88); primary tumor site: right colon 94(38.8%), left colon 148(61.2%); stage II 102(42.1%), stage III 81(33.5%), stage IV 59(24.4%). 5-fluorouracil based adjuvant chemotherapy was performed in 121 (66.1%) pts. After a median follow up of 30 months (1–80), 34 pts (10 pts stage II, 24 pts stage III) of 183 stage II-III pts (18.6%) had a disease recurrence. In a univariate analysis of stage II-III pts, a higher expression of Ki67 (= 50% positive cells) was significantly associated with an improved DFS (p= 0.014) and overall survival (OS) (p=0.010). Expression of p53, bcl-2, TS, EGFR, MLH1 and MSH2 were not significantly associated with DFS and OS. In a multivariate analysis adjusted for the impact of the disease stage and adjuvant chemotherapy, a higher expression of Ki67 was significantly associated with diminished risk of recurrence (HR: 0.395; 95% CI: 0.183–0.855, p=0.018) and death (HR: 0.179; 95% CI: 0.046–0.696, p=0.013). The evaluation of DNA mismatch repair status (MLH1, MSH2) demonstrated that the lack of MLH1 is more frequent in non-relapsed II-III stage pts than in IV stage pts (p= 0.024). Conclusions: This analysis showed a significant correlation between higher Ki67 expression and better DFS and OS in pts with stage II-III CRC. An higher frequency of MLH1 deficiency was observed in non-relapsed pts with stage II-III than in advanced disease. No significant financial relationships to disclose.

Lymphocytic response to tumour and deficient DNA mismatch repair identify subtypes of stage II/III colorectal cancer associated with patient outcomes

Gut ◽  
2018 ◽  
Vol 68 (3) ◽  
pp. 465-474 ◽  
Author(s):  
David S Williams ◽  
Dmitri Mouradov ◽  
Robert N Jorissen ◽  
Marsali R Newman ◽  
Elham Amini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Molecular Subtype ◽  
Survival Rates ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Dna Mismatch ◽  
Independent Cohort

ObjectiveTumour-infiltrating lymphocyte (TIL) response and deficient DNA mismatch repair (dMMR) are determinants of prognosis in colorectal cancer. Although highly correlated, evidence suggests that these are independent predictors of outcome. However, the prognostic significance of combined TIL/MMR classification and how this compares to the major genomic and transcriptomic subtypes remain unclear.DesignA prospective cohort of 1265 patients with stage II/III cancer was examined for TIL/MMR status and BRAF/KRAS mutations. Consensus molecular subtype (CMS) status was determined for 142 cases. Associations with 5-year disease-free survival (DFS) were evaluated and validated in an independent cohort of 602 patients.ResultsTumours were categorised into four subtypes based on TIL and MMR status: TIL-low/proficient-MMR (pMMR) (61.3% of cases), TIL-high/pMMR (14.8%), TIL-low/dMMR (8.6%) and TIL-high/dMMR (15.2%). Compared with TIL-high/dMMR tumours with the most favourable prognosis, both TIL-low/dMMR (HR=3.53; 95% CI=1.88 to 6.64; Pmultivariate<0.001) and TIL-low/pMMR tumours (HR=2.67; 95% CI=1.47 to 4.84; Pmultivariate=0.001) showed poor DFS. Outcomes of patients with TIL-low/dMMR and TIL-low/pMMR tumours were similar. TIL-high/pMMR tumours showed intermediate survival rates. These findings were validated in an independent cohort. TIL/MMR status was a more significant predictor of prognosis than National Comprehensive Cancer Network high-risk features and was a superior predictor of prognosis compared with genomic (dMMR, pMMR/BRAFwt/KRASwt, pMMR/BRAFmut/KRASwt, pMMR/BRAFwt/KRASmut) and transcriptomic (CMS 1-4) subtypes.ConclusionTIL/MMR classification identified subtypes of stage II/III colorectal cancer associated with different outcomes. Although dMMR status is generally considered a marker of good prognosis, we found this to be dependent on the presence of TILs. Prognostication based on TIL/MMR subtypes was superior compared with histopathological, genomic and transcriptomic subtypes.

Prognostic role of aberrant mTOR activation in patients with stage II and III colorectal cancer

2020 ◽  
Vol 14 (12) ◽  
pp. 1127-1137
Author(s):  
Tong-Tong Zhang ◽  
Yi-Qing Zhu ◽  
Hong-Qing Cai ◽  
Jun-Wen Zheng ◽  
Jia-Jie Hao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Poor Prognostic Factor ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Risk Predictor

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan–Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.

scholarly journals Methylation of the NT5E Gene Is Associated with Poor Prognostic Factors in Breast Cancer

Diagnostics ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 939
Author(s):  
Young Ju Jeong ◽  
Hoon Kyu Oh ◽  
Hye Ryeon Choi ◽  
Sung Hwan Park
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Methylation Status ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Receptor Expression ◽  
Gene Methylation ◽  
Clinicopathologic Characteristics ◽  
Large Tumor ◽  
The Mean

Cluster of differentiation (CD) 73, which is encoded by the NT5E gene, regulates production of immunosuppressive adenosine and is an emerging checkpoint in cancer immunotherapy. Despite the significance of CD73 in immuno-oncology, the roles of the NT5E gene methylation in breast cancer have not been well-defined yet. Therefore, we aimed to investigate the prognostic significance of the NT5E gene methylation in breast cancer. The DNA methylation status of the NT5E gene was analyzed using pyrosequencing in breast cancer tissues. In addition, the levels of inflammatory markers and lymphocyte infiltration were evaluated. The mean methylation level of the NT5E gene was significantly higher in breast cancer than in normal breast tissues. In the analysis of relevance with clinicopathologic characteristics, the mean methylation levels of the NT5E gene were significantly higher in patients with large tumor size, high histologic grade, negative estrogen receptor expression, negative Bcl-2 expression, and premenopausal women. There was no difference in disease-free survival according to the methylation status of the NT5E gene. We found that the NT5E gene methylation was related to breast cancer development and associated with poor prognostic factors in breast cancer. Our results suggest that the NT5E gene methylation has potential as an epigenetic biomarker in breast cancer.

scholarly journals Expression Patterns of Microenvironmental Factors and Tenascin-C at the Invasive Front of Stage II And III Colorectal Cancer: Novel Tumor Prognostic Markers

2021 ◽  
Author(s):  
Mai Hashimoto ◽  
Noriyuki Uesugi ◽  
Mitsumasa Osaka ◽  
Naoki Yanagawa ◽  
Koki Otsuka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Prognostic Markers ◽  
Multivariate Analyses ◽  
Expression Patterns ◽  
Stage Ii ◽  
High Expression ◽  
Disease Stage ◽  
Neoplastic Progression ◽  
Tenascin C

Abstract Background. Biological markers expressed in cancer cells and the surrounding cancer-associated fibroblasts (CAF) can be used for prediction of patient prognosis in colorectal cancer (CRC). Here, we used immunohistochemical techniques to evaluate cancer cells’ expression of specific biomarkers that are closely associated with neoplastic progression. Patients and Methods. Immunohistochemical markers included Ki-67, p53, β-catenin, MMP7, E-cadherin and HIF1-α. We also characterized microenvironmental markers expressed by CAF, including expression of α-smooth muscle actin, CD10, podoplanin, fibroblast specific protein 1, platelet derived growth factor β, fibroblast association protein, tenascin-C (TNC), ZEB1 and TWIST1. The study population consisted of 286 CRC patients with stage II and III disease. Stage II and III CRC were divided into a first and a second cohort (for validation). The CRCs were stratified using cluster analysis. To identify the utility of prognostic markers in stage II and III CRC, univariate and multivariate analyses were performed in both cohorts. Results. Stage II and III CRCs were stratified into 3 subgroups. Specific subgroups were significantly correlated to disease-free survival using univariate and multivariate analyses in the first cohort. High expression of TNC was identified as a single prognostic marker in both cohorts by univariate and multivariate analyses. Conclusions. We suggest that the presence of a specific subgroup defined by multiple markers can be used for prediction of CRC outcome in stages II and III. In addition, we showed that high expression of TNC was correlated with a poorer prognosis in stages II and III of CRC.

Prognostic significance of DNA ploidy in patients with stage II colorectal cancer

2001 ◽  
Vol 13 (1) ◽  
pp. 53-56
Author(s):  
Hong-yi Wang ◽  
Shan Jin ◽  
Zhong-qi Xue ◽  
Jin Gu ◽  
You-yong Lu
Keyword(s):  
Colorectal Cancer ◽  
Dna Ploidy ◽  
Prognostic Significance ◽  
Stage Ii ◽  
Stage Ii Colorectal Cancer

What is the Optimal Number of Lymph Nodes to be Dissected in Colorectal Cancer Surgery?

2005 ◽  
Vol 91 (2) ◽  
pp. 168-172 ◽  
Author(s):  
Mahmut Gumus ◽  
Perran Fulden Yumuk ◽  
Gul Atalay ◽  
Mehmet Aliustaoglu ◽  
Beyza Macunluoglu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Regional Lymph Node ◽  
Disease Free Survival ◽  
Optimal Number ◽  
Stage Ii ◽  
Term Outcome ◽  
Colorectal Cancer Surgery ◽  
Long Term Outcome ◽  
Surgical Specimen ◽  
Free Survival

Background Regional lymph node (LN) involvement in colorectal cancer (CRC) identifies the stage and the subset of patients who would benefit from adjuvant chemotherapy. We performed a retrospective analysis to determine if the number of recovered LNs was associated with long-term outcome in patients operated on for stage II and III CRC. Patients and methods Hospital records of 179 patients with CRC followed in our unit from 1997 to April 2003 were reviewed. Results On average 11.68 ± 7.3 LNs were sampled per surgical specimen. Sampling of at least nine LNs appeared to be the minimum number required for accurately predicting LN involvement ( P = 0.002). Three-year rates of disease-free survival (DFS), local recurrence-free survival (LRFS) and overall survival (OS) were lower in patients with fewer than nine LNs sampled ( P = 0.032, P = 0.006 and P = 0.04, respectively). However, this had no impact on the three-year distant metastasis-free survival rate (DMFS) ( P = 0.472). In stage II disease, patients with nine or more LNs dissected had significantly higher three year DFS and LRFS rates than the subgroup with fewer than nine LNs dissected ( P = 0.024 and P = 0.015, respectively), but this did not have any effect on DMFS or OS ( P = 0.406 and P = 0.353, respectively). Conclusion Current protocols provide adjuvant treatment in stage III patients; the problem is to correctly determine stage by recovering as many LNs as possible.

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