An Oxidative Stress Index-Based Score for Prognostic Prediction in Colorectal Cancer Patients Undergoing Surgery

Oxidative stress plays an important role in the development of colorectal cancer (CRC). This study is aimed at developing and validating a novel scoring system, based on oxidative stress indexes, for prognostic prediction in CRC patients. A retrospective analysis of 1422 CRC patients who underwent surgical resection between January 2013 and December 2017 was performed. These patients were randomly assigned to the training set ( n = 1022 ) or the validation set ( n = 400 ). Cox regression model was used to analyze the laboratory parameters. The CRC-Integrated Oxidative Stress Score (CIOSS) was developed from albumin (ALB), direct bilirubin (DBIL), and blood urea nitrogen (BUN), which were significantly associated with survival in CRC patients. Furthermore, a survival nomogram was generated by combining the CIOSS with other beneficial clinical characteristics. The CIOSS generated was as follows: 0.074 × albumin (g/L), − 0.094 × bilirubin (μmol/L), and - 0.099 × blood urea nitrogen (mmol/L), based on the multivariable Cox regression analysis. Using 50% (0.1025) and 85% (0.481) of CIOSS as cutoff values, three prognostically distinct groups were formed. Patients with high CIOSS experienced worse overall survival (OS) ( hazard ratio HR = 4.33 ; 95% confidence interval [CI], 2.80-6.68; P < 0.001 ) and worse disease-free survival (DFS) ( HR = 3.02 ; 95% CI, 1.96-4.64; P < 0.001 ) compared to those with low CIOSS. This predictive nomogram had good calibration and discrimination. ROC analyses showed that the CIOSS possessed excellent performance ( AUC = 0.818 ) in predicting DFS. The AUC of the OS nomogram based on CIOSS, TNM stage, T stage, and chemotherapy was 0.812, while that of the DFS nomogram based on CIOSS, T stage, and TNM stage was 0.855. Decision curve analysis showed that these two prediction models were clinically useful. CIOSS is a CRC-specific prognostic index based on the combination of available oxidative stress indexes. High CIOSS is a powerful indicator of poor prognosis. The CIOSS also showed better predictive performance compared to TNM stage in CRC patients.

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

Biomarkers in Medicine ◽

10.2217/bmm-2020-0141 ◽

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.

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Combination of CDX2 expression and T stage improves prognostic prediction of colorectal cancer

Journal of International Medical Research ◽

10.1177/0300060518819620 ◽

2019 ◽

Vol 47 (5) ◽

pp. 1829-1842 ◽

Cited By ~ 2

Author(s):

Weimin Xu ◽

Yilian Zhu ◽

Wei Shen ◽

Wenjun Ding ◽

Tingyu Wu ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Disease Free Survival ◽

Hazard Ratio ◽

Free Survival ◽

T Stage ◽

Cdx2 Expression ◽

Prognostic Prediction ◽

Disease Free

Objective Prognostic prediction of colorectal cancer (CRC) remains challenging because of its heterogeneity. Aberrant expression of caudal-type homeobox transcription factor 2 (CDX2) is strongly correlated with the prognosis of CRC. Methods Tissue samples of patients with CRC who underwent surgery in Xinhua Hospital (Shanghai, China) from January 2010 to January 2013 were collected. CDX2 expression was semiquantitatively evaluated via immunohistochemistry. Results In total, 138 patients were enrolled in this study from a prospectively maintained institutional cancer database. The median follow-up duration was 57.5 months (interquartile range, 17.0–71.0 months). In the Cox proportional hazards model, low CDX2 expression combined with stage T4 CRC was significantly the worst prognostic factor for disease-free survival (hazard ratio = 7.020, 95% confidence interval = 3.922–12.564) and overall survival (hazard ratio = 5.176, 95% CI = 3.237–10.091). In the Kaplan–Meier survival analysis, patients with low CDX2 expression and stage T4 CRC showed significantly worse disease-free survival and overall survival than those with low CDX2 expression alone. Conclusion CDX2 expression combined with the T stage was more accurate for predicting the prognosis of CRC. Determining the prognosis of CRC using more than one variable is valuable in developing appropriate treatment and follow-up strategies.

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Identification of lnc RNAs Related to Prognosis of Patients With Colorectal Cancer

Technology in Cancer Research & Treatment ◽

10.1177/1533033820962120 ◽

2020 ◽

Vol 19 ◽

pp. 153303382096212

Author(s):

Yuqi Sun ◽

Peng Peng ◽

Lanlan He ◽

Xueren Gao

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Cox Regression ◽

The Cancer Genome Atlas ◽

High Expression ◽

Cox Regression Analysis ◽

Cancer Genome Atlas ◽

Score Model ◽

Prognostic Prediction

The purpose of this study was to identify long noncoding RNAs (lncRNAs) related to prognosis of patients with colorectal cancer (CRC) and develop a prognostic prediction model for CRC. Transcriptome data and survival information of CRC patients were downloaded from The Cancer Genome Atlas. The differentially expressed lncRNAs (DElncRNAs) between CRC and normal colorectal tissues were identified by the edgeR package. The association of DElncRNAs expression with prognosis of CRC patients was analyzed by the survival package. A nomogram predicting 3- and 5- year overall survival of CRC patients was drawn by the rms package. A total of 1046 DElncRNAs were identified, including 271 down-regulated and 775 up-regulated lncRNAs in CRC. Multivariate Cox regression analysis showed 10 lncRNAs related to the prognosis of CRC patients. Thereinto high expression of AC004009.1, LHX1-DT, ELFN1-AS1, AL136307.1, AC087379.2, RBAKDN and AC078820.1 was associated with poorer prognosis of CRC patients. High expression of LINC01055, AL590483.1 and AC008514.1 was associated with better prognosis of CRC patients. Furthermore, the risk score model developed based on the 10 lncRNAs could effectively predict overall survival of CRC patients. In conclusion, 10 prognostic biomarkers for CRC were identified, which would be helpful to understand the role of lncRNAs in CRC progression.

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Serum Concentration of Genistein, Luteolin and Colorectal Cancer Prognosis

Nutrients ◽

10.3390/nu11030600 ◽

2019 ◽

Vol 11 (3) ◽

pp. 600 ◽

Cited By ~ 1

Author(s):

Ruijingfang Jiang ◽

Gernot Poschet ◽

Robert Owen ◽

Muhabbet Celik ◽

Lina Jansen ◽

...

Keyword(s):

Colorectal Cancer ◽

Adjuvant Chemotherapy ◽

Serum Concentration ◽

Cox Regression ◽

Disease Free Survival ◽

Ultra Performance Liquid Chromatography ◽

Population Based ◽

Potential Interaction ◽

Cancer Prognosis ◽

Cox Regression Analysis

Although flavonoid phytoestrogens have been suggested to be associated with reduced risk of colorectal cancer (CRC), their influence on CRC prognosis remains uncertain. A population-based cohort of 2051 patients diagnosed with stage I–III CRC in southwest Germany in 2003–2010 were followed for five years. Post-diagnostic serum concentration of genistein and luteolin were measured using Ultra-Performance Liquid Chromatography with mass spectrometry. Multivariable Cox regression analysis was conducted to calculate the Hazard Ratios (HRs) and 95% confidence interval (CI) for the association between flavonoids concentration and overall morality, CRC-specific mortality, CRC recurrence, and disease-free survival (DFS). Median (interquartile range) serum concentration of genistein and luteolin was 11.90 ng/µL (10.08–14.13) and 7.20 ng/µL (6.40–8.16), respectively. Neither serum genistein nor luteolin was associated with CRC prognosis. There was no clear evidence of departure from linearity. However, the association might be differential by adjuvant chemotherapy. Associations pointed towards lower risk in patients who received chemotherapy and higher risk in those without chemotherapy for overall mortality regarding serum genistein (P-interaction = 0.02) and correspondingly for CRC recurrence (P-interaction: 0.03) and DFS (P-interaction: 0.01) with respect to luteolin. Our study provides little evidence that serum genistein and luteolin are associated with colorectal cancer prognosis. Future studies are warranted to evaluate the potential interaction with adjuvant chemotherapy.

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A prognostic index based on an eleven gene signature to predict systemic recurrences in colorectal cancer

Experimental & Molecular Medicine ◽

10.1038/s12276-019-0319-y ◽

2019 ◽

Vol 51 (10) ◽

pp. 1-12 ◽

Cited By ~ 2

Author(s):

Seon-Kyu Kim ◽

Seon-Young Kim ◽

Chan Wook Kim ◽

Seon Ae Roh ◽

Ye Jin Ha ◽

...

Keyword(s):

Colorectal Cancer ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Biological Diversity ◽

Cox Regression ◽

Prognostic Index ◽

Gene Signature ◽

Rt Pcr ◽

Transcriptomic Profiling ◽

Cox Regression Analysis

Abstract Approximately half of colorectal cancer (CRC) patients experience disease recurrence and metastasis, and these individuals frequently fail to respond to treatment due to their clinical and biological diversity. Here, we aimed to identify a prognostic signature consisting of a small gene group for precisely predicting CRC heterogeneity. We performed transcriptomic profiling using RNA-seq data generated from the primary tissue samples of 130 CRC patients. A prognostic index (PI) based on recurrence-associated genes was developed and validated in two larger independent CRC patient cohorts (n = 795). The association between the PI and prognosis of CRC patients was evaluated using Kaplan–Meier plots, log-rank tests, a Cox regression analysis and a RT-PCR analysis. Transcriptomic profiling in 130 CRC patients identified two distinct subtypes associated with systemic recurrence. Pathway enrichment and RT-PCR analyses revealed an eleven gene signature incorporated into the PI system, which was a significant prognostic indicator of CRC. Multivariate and subset analyses showed that PI was an independent risk factor (HR = 1.812, 95% CI = 1.342–2.448, P < 0.001) with predictive value to identify low-risk stage II patients who responded the worst to adjuvant chemotherapy. Finally, a comparative analysis with previously reported Consensus Molecular Subgroup (CMS), high-risk patients classified by the PI revealed a distinct molecular property similar to CMS4, associated with a poor prognosis. This novel PI predictor based on an eleven gene signature likely represents a surrogate diagnostic tool for identifying high-risk CRC patients and for predicting the worst responding patients for adjuvant chemotherapy.

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Enhancing the Landscape of Colorectal Cancer Using Targeted Deep Sequencing

10.20944/preprints202009.0483.v1 ◽

2020 ◽

Author(s):

Chul Seung Lee ◽

In Hye Song ◽

Ahwon Lee ◽

Jun Kang ◽

Yoon Suk Lee ◽

...

Keyword(s):

Colorectal Cancer ◽

Poor Prognosis ◽

Cox Regression ◽

Disease Free Survival ◽

Tumor Stage ◽

Underlying Disease ◽

Clinicopathological Characteristics ◽

Oncologic Outcomes ◽

Cox Regression Analysis ◽

Targeted Next Generation Sequencing

Targeted next-generation sequencing (NGS) technology detects specific mutations that can provide treatment opportunities for colorectal cancer (CRC) patients. We included 145 CRC patients who underwent surgery. We analyzed the mutation frequencies of common actionable genes and their association with clinicopathological characteristics and oncologic outcomes using targeted NGS. Approximately 97.9% (142) of patients showed somatic mutations. Frequent mutations were observed in TP53 (70%), KRAS (49%), and APC (47%). TP53 mutations were significantly linked to higher overall stage (p=0.038) and lower disease-free survival (DFS) (p=0.039). ATM mutation was significantly associated with higher tumor stage (p=0.012) and shorter overall survival (OS) (p=0.041). Stage 3 and 4 patients with ATM mutations (p=0.023) had shorter OS, and FBXW7 mutation was significantly associated with shorter DFS (p=0.002). In multivariate Cox regression analysis, ATM mutation was an independent biomarker for poor prognosis of OS (p=0.022). TP53 and FBXW7 mutations are independent biomarkers for poor prognosis of DFS (p=0.042 and 0.030, respectively). A comprehensive analysis of the molecular markers for CRC can provide insights into the mechanisms underlying disease progression and help optimize a personalized therapy.

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A Prognostic Model Based on the Immune-Related lncRNAs in Colorectal Cancer

Frontiers in Genetics ◽

10.3389/fgene.2021.658736 ◽

2021 ◽

Vol 12 ◽

Author(s):

Fengxia Qin ◽

Houxi Xu ◽

Guoli Wei ◽

Yi Ji ◽

Jialin Yu ◽

...

Keyword(s):

Colorectal Cancer ◽

Risk Score ◽

Cox Regression ◽

Prognostic Index ◽

The Cancer Genome Atlas ◽

Differentially Expressed ◽

Prognostic Indicators ◽

Cox Regression Analysis ◽

Model Based ◽

Cancer Tissues

BackgroundColorectal cancer (CRC) is one of the most common malignant tumors with a poor prognosis. At present, the pathogenesis is not completely clear. Therefore, finding reliable prognostic indicators for CRC is of important clinical significance. In this study, bioinformatics methods were used to screen the prognostic immune-related lncRNAs of CRC, and a prognostic risk scoring model based on immune-related lncRNAs signatures were constructed to provide a basis for prognostic evaluation and immunotherapy of CRC patients.MethodsThe clinical information and RNA-seq data of CRC patients were obtained from The Cancer Genome Atlas (TCGA) database. The information of immune-related lncRNA was downloaded from the immunology database and analysis portal. The differentially expressed immune-related lncRNAs (IRLs) were screened by the edgeR package of R software. The prognostic value of IRLs was studied. Based on Cox regression analysis, a prognostic index (IRLPI) based on IRLs was established, and the relationship between the risk score and the clinicopathological characteristics of CRC was analyzed to determine the effectiveness of the risk score model as an independent prognostic factor.ResultsA total of 240 differentially expressed IRLs were identified between normal colorectal cancer tissues and normal colorectal cancer tissues, in which 8 were significantly associated with the survival of CRC patients (P < 0.05), including LINC00461, LINC01055, ELFN1-AS1, LMO7-AS1, CYP4A22-AS1, AC079612.1, LINC01351, and MIR31HG. And most of the lncRNAs related to survival were risk factors for the prognosis of CRC. The index established based on the 7 survival-related IRLs found to be highly accurate in monitoring CRC prognosis. Besides, IRLPI was significantly correlated with a variety of pathological factors and immune cell infiltration.ConclusionEight immune-related lncRNAs closely related to the prognosis of CRC patients were identified from the TCGA database. At the same time, an independent IRLPI was constructed, which may be helpful for clinicians to assess the prognosis of patients with CRC and to formulate individualized treatment plans.

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The Combination of Inflammation and Nutrition Factors Reinforces the Prognostic Prediction for Stage III Colorectal Cancer Patients After Curative Resection

10.21203/rs.3.rs-1226522/v1 ◽

2022 ◽

Author(s):

Shinya Kato ◽

Norikatsu Miyoshi ◽

Shiki Fujino ◽

Soichiro Minami ◽

Chu Matsuda ◽

...

Keyword(s):

Colorectal Cancer ◽

Cox Regression ◽

Prognostic Score ◽

Disease Free Survival ◽

Albumin Level ◽

Stage Iii ◽

Curative Surgery ◽

Validation Set ◽

Prognostic Prediction ◽

Colorectal Cancer Patients

Abstract Purpose Inflammation and nutritional status are known to be associated with the prognosis of several malignancies. Herein, we attempted to develop inflammation–nutrition scores and predict the prognosis of stage III colorectal cancer (CRC). Methods This retrospective study included 262 patients with stage III CRC who underwent curative surgery and were divided into two groups: a training set (TS) of 162 patients and a validation set (VS) of 100 patients. In the TS, clinicopathological factors were tested using a Cox regression model, and the Kansai prognostic score (KPS) was assessed by 1 point each for <3.5 g/dL albumin level, >450 monocyte counts, and <1.65 × 105 platelet counts, which were associated with disease-free survival (DFS). Using KPS, DFS and overall survival (OS) were validated in VS. Results The C-indices of KPS to predict DFS and OS in TS were 0.707 and 0.772. It was validated in VS that the C-indices of KPS to predict DFS and OS were 0.618 and 0.708, respectively. A high KPS was a significant predictor of DFS and OS. Conclusion KPS serves as a new model for the prognosis of patients with stage III CRC.

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Exploration of the Key Proteins in the Normal-Adenoma-Carcinoma Sequence of Colorectal Cancer Evolution Using In-Depth Quantitative Proteomics

Journal of Oncology ◽

10.1155/2021/5570058 ◽

2021 ◽

Vol 2021 ◽

pp. 1-19

Author(s):

Yin Zhang ◽

Chun-Yuan Li ◽

Wei Ge ◽

Yi Xiao

Keyword(s):

Colorectal Cancer ◽

Quantitative Proteomics ◽

Prognostic Value ◽

Cox Regression ◽

Epithelial Mesenchymal Transition ◽

Disease Free Survival ◽

Gene Set Enrichment Analysis ◽

Mesenchymal Transition ◽

Cox Regression Analysis ◽

Proteomic Data

Purpose. In most cases, the carcinogenesis of colorectal cancer (CRC) follows the normal-adenoma-carcinoma (N-A-C) sequence. In this study, we aimed to identify the key proteins in the N-A-C sequence. Methods. Differentially expressed proteins (DEPs) in normal, adenoma, and carcinoma tissues were identified using the Tandem Mass Tag- (TMT-) based quantitative proteomics approach. The landscape of proteomic variation in the N-A-C sequence was explored using gene set enrichment analysis (GSEA) and Proteomaps. Key proteins in the N-A-C sequence were identified, verified, and validated based on our proteomic data, external proteomic data, and external transcriptomic data in the ProteomeXchange, CPTAC, GEO, and TCGA databases. The prognostic value of the key proteins in our database was evaluated by univariate and multivariate Cox regression analysis. The effects of the key proteins on adenoma organoids and colorectal cancer cells were explored in functional studies. Results. Based on our proteomic profiles, we identified 1,294 DEPs between the carcinoma (CG) and normal (NG) groups, 919 DEPs between the adenoma group (AG) and NG, and 1,030 DEPs between the CG and AG. Ribosome- and spliceosome-related pathways were mainly enriched in the N-A process. Extracellular matrix- and epithelial-mesenchymal transition- (EMT-) related pathways were mainly enriched in the A-C process. RRP12 and SERPINH1 were identified, verified, and validated as candidate key proteins in the N-A and A-C processes, respectively. Furthermore, RRP12 and SERPINH1 knockdown impeded the viability and proliferation of adenoma organoids. SERPINH1 was validated as a risk factor for disease-free survival (DFS) based on the TCGA and our database, whereas RRP12 did not show prognostic value. SERPINH1 knockdown was accompanied by EMT-related protein variation, increased apoptosis, and reduced proliferation, invasion, and migration of CRC cells in vitro. Conclusions. RRP12 and SERPINH1 may play an important role in the N-A and A-C processes, respectively. Furthermore, SERPINH1 showed favorable prognostic value for DFS in CRC patients. We speculate that SERPINH1 might promote not only the A-C process but also the development of CRC.

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Treatment of colorectal cancer in Armenia: A retrospective hospital-based study from a developing world.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16099 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16099-e16099

Author(s):

Samvel Bardakhchyan ◽

Sergo Mkhitaryan ◽

Davit Zohrabyan ◽

Liana Safaryan ◽

Armen Avagyan ◽

...

Keyword(s):

Colorectal Cancer ◽

Adjuvant Chemotherapy ◽

Median Survival ◽

Cox Regression ◽

Survival Rates ◽

Disease Free Survival ◽

Rectum Cancer ◽

Cox Regression Analysis ◽

Stage 4 ◽

Significant Difference

e16099 Background: In Armenia colorectal cancer (CRC) is on the third place by incidence. Every year around 700 new cases are diagnosed with 60% diagnosed in 3rd and 4th stages. Methods: For this retrospective hospital-based study we have collected data from two main oncology centers in Armenia: National Oncology Center and Muratsan Hospital Complex of Yerevan state medical university. The information about patients with CRC who were treated at these two centers during 01/01/2010 - 07/01/2018 period was collected from the medical records. Results: 602 patients with CRC treated during mentioned period in these two hospitals were involved in final analysis. From them 51.8% were female. Median age at diagnosis was 58. Median follow up time was 37 months (range 3-207). 26.1% had right sided, 30.9% left sided and 43.0% rectum cancer. 8.6% of patients had stage 1, 32.9% stage 2, 38.0% stage 3, 17.6% stage 4 CRC and for 2.7% patients stage was unknown. The median survival was not reached for the entire cohort ( > 37 months). Median survival was > 66.5 months for 1st, > 48.5 months for 2nd, > 35 months for 3rd and 19 months for 4th stages. Tumor stage, grade and histology were the main independent prognostic factors by univariate and multivariate Cox regression analysis. For stage 2 CRC patients (198) we found significant difference regarding overall survival (OS) (p = 0.024) and disease free survival (DFS) (p = 0.006) for those who received adjuvant chemotherapy after surgery compared to those who didn’t receive adjuvant chemotherapy. For stage 2 and 3 rectum cancer patients, our study failed to show OS (2nd stage: p = 0.961; 3rd stage: p = 0.348) or DFS (2nd stage: p = 0.719; 3rd stage: p = 0.983) advantage for those who received radiotherapy (RT) compared with those who didn’t receive RT. In our study population 28.3% of stage 4 patients received chemotherapy combined with Bevacizumab while 70% were treated with chemotherapy only. Median OS between these two groups wasn’t significantly different (21 months in Chemo+Bevacizumab group and 18.5 months in chemo only group (p = 0.382)). 3 and 5-year survival rates were 62.9% and 51.8% for all stages combined and 79.7% and 68.5% for stages 1-2, 62.5% and 48.4% for stage 3, 24.4% and 17% for stage 4 respectively. Conclusions: As seen from our results our survival rates are inferior compared to that of developed world. The reasons for that could be compromise in surgery and RT, poor pathological assessment, unavailability of some molecular markers, poor availability of new targeted drugs and absence of national treatment guidelines.

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