scholarly journals Clinicopathological Features Combined With Immune Infiltration Could Well Distinguish Outcomes in Stage II and Stage III Colorectal Cancer: A Retrospective Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiazi Ren ◽  
Linfeng Xu ◽  
Siyu Zhou ◽  
Jian Ouyang ◽  
Weiqiang You ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Good Accuracy ◽  
Disease Free Survival ◽  
Risk Groups ◽  
Clinicopathological Characteristics ◽  
Stage Ii ◽  
Prognostic Models ◽  
Risk Scores ◽  
Pn Stage ◽  
Multidimensional Models

BackgroundThe Immunoscore predicts prognosis in patients with colorectal cancer (CRC). However, a few studies have incorporated the Immunoscore into the construction of comprehensive prognostic models in CRC, especially stage II CRC. We aimed to construct and validate multidimensional models integrating clinicopathological characteristics and the Immunoscore to predict the prognosis of patients with stage II–III CRC.MethodsPatients (n = 254) diagnosed with stage II–III CRC from 2009 to 2016 were used to generate Cox models for predicting disease-free survival (DFS) and overall survival (OS). The variables included basic clinical indicators, blood inflammatory markers, preoperative tumor biomarkers, mismatch repair status, and the Immunoscore (CD3+ and CD8+ T-cell densities). Univariate and multivariate Cox proportional regressions were used to construct the prognostic models for DFS and OS. We validated the predictive accuracy and ability of the prognostic models in our cohort of 254 patients.ResultsWe constructed two predictive prognostic models with C-index values of 0.6941 for DFS and 0.7138 for OS in patients with stage II–III CRC. The Immunoscore was the most informative predictor of DFS (11.92%), followed by pN stage, carcinoembryonic antigen (CEA), and vascular infiltration. For OS, the Immunoscore was the most informative predictor (8.59%), followed by pN stage, age, CA125, and CEA. Based on the prognostic models, nomograms were developed to predict the 3- and 5-year DFS and OS rates. Patients were divided into three risk groups (low, intermediate, and high) according to the risk scores obtained from the nomogram, and significant differences were observed in the recurrence and survival of the different risk groups (p < 0.0001). Calibration curve and time-dependent receiver operating characteristic (ROC) analysis showed good accuracy of our models. Furthermore, the decision curve analysis indicated that our nomograms had better net benefit than pathological TNM (pTNM) stage within a wide threshold probability. Especially, we developed a website based on our prognostic models to predict the risks of recurrence and death of patients with stage II–III CRC.ConclusionsMultidimensional models including the clinicopathological characteristics and the Immunoscore were constructed and validated, with good accuracy and convenience, to evaluate the risks of recurrence and death of stage II–III CRC patients.

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 HER2 and BRAF mutation in colorectal cancer patients: a retrospective study in Eastern China

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8602 ◽  
Author(s):  
Xiangyan Zhang ◽  
Jie Wu ◽  
Lili Wang ◽  
Han Zhao ◽  
Hong Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Eastern China ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Molecular Classification ◽  
Clinicopathological Characteristics ◽  
Stage I ◽  
Chinese Patients ◽  
Poor Differentiation ◽  
Colorectal Cancer Patients

Objective To investigate the frequency and prognostic role of the human epidermal growth factor receptor 2 gene (HER2) and BRAF V600E gene mutation in Chinese patients with colorectal cancer (CRC). Methods Clinicopathological and survival information from 480 patients with stage I–III CRC were reviewed and recorded. HER2 amplification was analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), BRAF V600E mutation was tested by IHC and Sanger sequencing. The relationship between HER2 and BRAF V600E mutation status and clinicopathological characteristics and outcomes were determined. Results The amplification of HER2 and BRAF V600E mutation were identified in 27 of 480 (5.63%) and 19 of 480 (3.96%) CRC patients, respectively. HER2 amplification significantly correlated with greater bowel wall invasion (P = 0.041) and more advanced TNM stage (I vs. II vs. III; 0 vs 5.78% vs. 7.41%, P = 0.013). Patients suffering from tumors with poor differentiation had a higher incidence rate of BRAF V600E mutation than those with moderate/well differentiation (7.77% vs 2.92%, P = 0.04). HER2 amplification was an independent prognostic factor for worse disease-free survival (DFS) (HR = 2.53, 95% CI: 1.21–5.30, P = 0.014). Conclusion The prevalence of HER2 amplification and BRAF V600E mutation in stage I–III CRC patients in Chinese was 6% and 4%, respectively, and HER2 amplification appeared to be associated with a worse DFS. More comprehensive molecular classification and survival analysis are needed to validate our findings.

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.

scholarly journals Personalizing the Prediction of Colorectal Cancer Prognosis by Incorporating Comorbidities and Functional Status into Prognostic Nomograms

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1435 ◽  
Author(s):  
Daniel Boakye ◽  
Lina Jansen ◽  
Martin Schneider ◽  
Jenny Chang-Claude ◽  
Michael Hoffmeister ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Functional Status ◽  
Significant Risk ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Tumor Location ◽  
Cancer Prognosis ◽  
Prognostic Models ◽  
Cox Models ◽  
Validation Set

Despite consistent evidence that comorbidities and functional status (FS) are strong prognostic factors for colorectal cancer (CRC) patients, these important characteristics are not considered in prognostic nomograms. We assessed to what extent incorporating these characteristics into prognostic models enhances prediction of CRC prognosis. CRC patients diagnosed in 2003–2014 who were recruited into a population-based study in Germany and followed over a median time of 4.7 years were randomized into training (n = 1608) and validation sets (n = 1071). In the training set, Cox models with predefined variables (age, sex, stage, tumor location, comorbidity scores, and FS) were used to construct nomograms for relevant survival outcomes. The performance of the nomograms, compared to models without comorbidity and FS, was evaluated in the validation set using concordance index (C-index). The C-indexes of the nomograms for overall and disease-free survival in the validation set were 0.768 and 0.737, which were substantially higher than those of models including tumor stage only (0.707 and 0.701) or models including stage, age, sex, and tumor location (0.749 and 0.718). The nomograms enabled significant risk stratification within all stages including stage IV. Our study suggests that incorporating comorbidities and FS into prognostic nomograms could substantially enhance prediction of CRC prognosis.

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.

Effect of preoperative hepatic and regional arterial chemotherapy on metachronous liver metastasis after curative colorectal cancer resection: A prospective, multicenter, randomized controlled trial.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 511-511
Author(s):  
Jianmin Xu ◽  
Jianguo Xia ◽  
Yan Gu ◽  
Jianjiang Lin ◽  
Kefeng Ding ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Adjuvant Therapy ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Stage Iii ◽  
Metachronous Liver Metastasis ◽  
Colorectal Cancer Resection ◽  
Multicenter Randomized Controlled Trial ◽  
Metastasis Rate

511 Background: To evaluate the addition of preoperative hepatic and regional arterial chemotherapy (PHRAC) on prognosis for stage II and III colorectal cancer in a multicenter setting. Methods: Patients with clinical stage II or stage III colorectal cancer (CRC) were randomly assigned to receive PHRAC plus adjuvant therapy (PHRAC arm) or adjuvant therapy alone (control arm). The primary end point was disease free survival (DFS). Second end points were incidence of metachronous liver metastasis, overall survival (OS) and safety. Results: A total of 688 patients from 5 centers of China were randomly assigned to each arm. Five-year DFS were 75% for PHRAC arm and 61% for control arm (HR 0.60; 95% CI, 0.45 to 0.80; p<0.001). Five-year liver-metastasis rate was 8% and 18% in PHRAC arm and control arm, respectively (HR 0.39; 95% CI, 0.24 to 0.64; p<0.001). Five-year OS was 81% in PHRAC arm and 72% in control arm (HR 0.59; 95% CI, 0.42 to 0.84; p=0.003). There were no significant differences in morbidity or mortality between two arms. The results of eligible patients were barely changed. Subgroup analysis shows differences of DFS, liver-metastasis rate and OS were significant in stage III patients, but not in stage II patients. Conclusions: Additional PHRAC could reduce the incidence of metachronous liver metastasis and improve DFS and OS in patients with stage III CRC, without compromising patient safety. Clinical trial information: NCT00643877.

Comorbidity and systemic inflammation are independent prognostic factors in patients with colorectal cancer: A ScotScan collaborative study.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 707-707
Author(s):  
James Hugh Park ◽  
Anniken Fuglestad ◽  
Anne Helene Kostner ◽  
Antonia K. Roseweir ◽  
Joanne Edwards ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Systemic Inflammation ◽  
Inflammatory Responses ◽  
Prognostic Score ◽  
Collaborative Study ◽  
Glasgow Prognostic Score ◽  
Clinicopathological Characteristics ◽  
Stage Ii ◽  
Royal Infirmary ◽  
Modified Glasgow Prognostic Score

707 Background: Although inextricably linked, both comorbidity and systemic inflammatory responses have been shown to determine survival in patients undergoing surgery for colorectal cancer (CRC). The present study examines the interrelationships between comorbidity (ASA grade) and systemic inflammation (modified Glasgow Prognostic Score (mGPS)) in patients from the ScotScan dataset. Methods: Clinicopathological characteristics and outcome of consecutive patients undergoing potentially curative resection of TNM I-III CRC in Glasgow Royal Infirmary (Scotland) and Sørlandet Hospital (Norway) were prospectively collected. ASA grade and mGPS (0-CRP ≤ 10mg/L, 1-CRP > 10mg/L, 2-CRP > 10mg/L and albumin < 35g/L) prior to surgery was recorded and relationship with overall survival (OS) examined. Results: 2,295 patients (Scotland: n = 1,234 , Norway: n = 1,061) were included. Patients from Norway were more likely to be older, female and have higher ASA grade (all P < 0.001), and more likely to have colon cancer (76% vs. 67%, P < 0.001). Patients from Norway were less likely to be systemically inflamed (mGPS = 0: 72% vs. 65%, P < 0.001), even after propensity score matching ( n = 736, OR 0.36 95%CI0.25-0.51, P < 0.001). ASA grade and mGPS were significantly associated; 21% of ASA 1 patients had mGPS ≥ 1 compared to 41% of ASA four patients ( P < 0.001). In the propensity-matched cohort, both increasing ASA (HR 1.98 95% CI1.57-2.49, P < 0.001) and mGPS (HR 1.20 95% CI1.02-1.41, P = 0.027) were associated with OS independent of age, N stage and adjuvant therapy use; results in the whole cohort were similar. The combination of ASA grade and mGPS was examined with respect to OS in patients with stage II-III CRC (Table 1). In patients with stage II disease, 3-year OS was stratified from 96% (ASA 1, mGPS0) to 67% (ASA 3, mGPS2) ( P < 0.001); in patients with stage II disease, 3-year OS was stratified from 84% to 44% ( P < 0.001). Conclusions: Using a large, prospectively collected dataset of patients undergoing resection of CRC in two countries, the results of the present study confirm the independent prognostic value of measures of comorbidity and systemic inflammation prior to surgery.

scholarly journals Genome-Wide Analysis Reveals Hypoxic Microenvironment Is Associated With Immunosuppression in Poor Survival of Stage II/III Colorectal Cancer Patients

2021 ◽  
Vol 8 ◽  
Author(s):  
Yu-feng Chen ◽  
Zhao-liang Yu ◽  
Min-yi Lv ◽  
Bin Zheng ◽  
Ying-xin Tan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Disease Free Survival ◽  
Enrichment Analysis ◽  
Gene Signature ◽  
Stage Ii ◽  
Free Survival ◽  
Genome Wide ◽  
Colorectal Cancer Patients ◽  
Worse Prognosis

Background: Hypoxia is associated with a poorer clinical outcome and resistance to chemotherapy in solid tumors; identifying hypoxic-related colorectal cancer (CRC) and revealing its mechanism are important. The aim of this study was to assess hypoxia signature for predicting prognosis and analyze relevant mechanism.Methods: Patients without chemotherapy were selected for the identification of hypoxia-related genes (HRGs). A total of six independent datasets that included 1,877 CRC patients were divided into a training cohort and two validation cohorts. Functional annotation and analysis were performed to reveal relevant mechanism.Results: A 12-gene signature was derived, which was prognostic for stage II/III CRC patients in two validation cohorts [TCGA, n = 509, hazard ratio (HR) = 2.14, 95% confidence interval (CI) = 1.18 – 3.89, P = 0.01; metavalidation, n = 590, HR = 2.46, 95% CI = 1.59 – 3.81, P &lt; 0.001]. High hypoxic risk was correlated with worse prognosis in CRC patients without adjuvant chemotherapy (HR = 5.1, 95% CI = 2.51 – 10.35, P &lt; 0.001). After integration with clinical characteristics, hypoxia-related gene signature (HRGS) remained as an independent prognostic factor in multivariate analysis. Furthermore, enrichment analysis found that antitumor immune response was suppressed in the high hypoxic group.Conclusions: HRGS is a promising system for estimating disease-free survival of stage II/III CRC patients. Hypoxia tumor microenvironment may be via inhibiting immune response to promote chemoresistance in stage II/III CRC patients.

The correlation between mismatch repair status and clinicopathological characteristics in Chinese colorectal cancer patients.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 544-544 ◽  
Author(s):  
Zhi-tao Xiao ◽  
Rong-xin Zhang ◽  
Yang Zhao ◽  
Jian-Hong Peng ◽  
Pei-Rong Ding ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Mismatch Repair ◽  
Mucinous Adenocarcinoma ◽  
Clinicopathological Characteristics ◽  
Left Colon ◽  
Stage Ii ◽  
Chinese Patients ◽  
Right Colon ◽  
Significant Difference

544 Background: Our study aimed to explore the relationship between mismatch repair (MMR) status and clinicopathological characteristics in Chinese patients with colorectal cancer (CRC). Methods: A total of 2684 patients with histologically confirmed adenocarcinoma of CRC were consecutively recruited between May 2011 and May 2015 at Sun Yat-sen University cancer center. The exclusion criteria included multiple primary tumors, synchronous and metachronous CRC, and familial adenomatous polyposis. The CRC was defined as left colon with the tumor located below the splenic flexure or rectum, otherwise grouped as right colon. Correlations of MMR status and patient’s demographics, tumor characteristics and TNM staging (exclude 315 CRC patients receiving neoadjuvant therapy) were investigated. Results: We found that deficient MMR (dMMR) status was more likely detected in younger CRC patients compared to the the elderly (12.7% vs 7.5%, P < 0.001). The dMMR rate in right colon cancer was significantly higher than that in left colon cancer and rectal cancer (22.7% vs 7.2% vs 5.2%, P < 0.001).With respect to tumor differentiation, we found that the mucinous adenocarcinoma had the highest rate of dMMR(24.4%), followed by poorly differentiated adenocarcinoma(18.5%), signet-ring cell carcinoma(17.6%), well differentiated adenocarcinoma(9.5%), moderately differentiated adenocarcinoma(8.9%), and neuroendocrine carcinoma (0%) ( P < 0.001). In addition, the proportions in stage I, stage II, stage III and stage IV CRC were 9.7%, 16.5% , 8.5% and 3.9%, respectively ( P < 0.001). There was no significant difference in gender (P = 0.114). Conclusions: At the first time, our study demonstrated that dMMR status was most likely detected at younger age (less than 59 years) and stage II right colon mucinous adenocarcinoma in large volume Chinese patients, which was similar to the results in western countries.

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