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

Shinya Kato ◽  
Norikatsu Miyoshi ◽  
Shiki Fujino ◽  
Soichiro Minami ◽  
Chu Matsuda ◽  

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.

Tumor Biology ◽  
2019 ◽  
Vol 41 (6) ◽  
pp. 101042831984623 ◽  
Elisabeth Odin ◽  
Arvid Sondén ◽  
Göran Carlsson ◽  
Bengt Gustavsson ◽  
Yvonne Wettergren

5-fluorouracil in combination with the folate leucovorin is the cornerstone in treatment of colorectal cancer. Transport of leucovorin into cells, and subsequent metabolic action, require expression of several genes. The aim was to analyze if tumoral expression of genes putatively involved in leucovorin transport, polyglutamation, or metabolism was associated with outcome of patients with stage III colorectal cancer treated with adjuvant chemotherapy. A total of 363 stage III colorectal cancer patients who received adjuvant bolus 5-fluorouracil + leucovorin alone, or in combination with oxaliplatin according to Nordic bolus regimes were included. Expression of 11 folate pathway genes was determined in tumors using quantitative real-time polymerase chain reaction and related to disease-free survival. The median follow-up time was 5 years. During follow-up, 114 (31%) patients suffered from recurrent disease. A high tumoral expression of the genes SLC46A1/PCFT, SLC19A1/RFC-1, ABCC3/MRP3, GGH, and MTHFD1L, which are involved in folate transport, polyglutamation, or metabolism, was associated with longer disease-free survival of the patients. Each of these genes either encodes mitochondrial enzymes or is being regulated by mitochondrial transcription factors. Expression of the SLC46A1/PCFT gene was most strongly associated with disease-free survival, regardless of treatment regimen. In conclusion, the results show that expression of folate pathway genes are associated with outcome of colorectal cancer patients treated with adjuvant 5-fluorouracil in combination with leucovorin. A prospective study needs to be conducted to determine if expression of these genes can be used to predict response to leucovorin and other folates that are now being tested in clinical studies. Moreover, there seems to be a link between folate metabolism and mitochondrial biogenesis and respiration that deserves further exploration.

2020 ◽  
Jie Li ◽  
Yuan-Yi Rui ◽  
Bo Song ◽  
Ke Zhang ◽  
Bo Yi ◽  

Abstract Background: The aim of this study was to find that if the red cell distribution width (RDW) or hemoglobin (Hb) level variations had prognostic value in stage III colorectal cancer patients treated with operation and adjuvant chemotherapy. Methods: One hundred and twenty-two patients were included in this retrospective study. All were diagnosed and re-staged as stage III colorectal cancer in Sichuan Cancer Hospital according to the AJCC Cancer Staging Manual, 8 th edition, 2018. The patients received R0 resection before adjuvant chemotherapy. The baseline information, routine blood examination data, pathological outcome and prognostic stature was retracted from the database. Receiver operating characteristic (ROC) curve analysis was utilized to determine the cut-off value, while the survival analyses were performed with Kaplan-Meier curve, the log-rank test and the Cox regression analysis. Results: The chemotherapy-associated hemoglobin change (change between the pre- and post-chemotherapy hemoglobin levels) was identified to be associated with the metastasis (P=0.030). The optimal cut-off point was calculated to be -9.5 by the ROC curve of the hemoglobin change, while the area under the curve was 0.648 (95% CI: 0.524-0.772). The results showed that patients with larger hemoglobin decrease had significantly worse disease free survival (DFS) than those with smaller decrease (P=0.020). Factors associated with DFS in uni-variate COX regression analysis were the number of harvested lymph nodes (P=0.040) and the perineural invasion (P=0.020). The peri-chemotherapy change of hemoglobin level was estimated to have significant effect on patient survival (P=0.010). Conclusions: We concluded that chemotherapy-associated Hb change (change between the pre- and post-chemotherapy) was a DFS prognostic factor for the stage III colorectal cancer patients who underwent operation and adjuvant chemotherapy.

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Yinghao Cao ◽  
Shenghe Deng ◽  
Lizhao Yan ◽  
Junnan Gu ◽  
Fuwei Mao ◽  

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.

2011 ◽  
Vol 29 (12) ◽  
pp. 1547-1555 ◽  
Hisae Iinuma ◽  
Toshiaki Watanabe ◽  
Koshi Mimori ◽  
Miki Adachi ◽  
Naoko Hayashi ◽  

Purpose Using multiple genetic markers, including cancer stem-like cells, we evaluated the clinical significance of circulating tumor cells (CTCs) as a prognostic factor for overall survival (OS) and disease-free survival (DFS) in the peripheral blood (PB) of patients with colorectal cancer (CRC) who had undergone curative surgery. Patients and Methods In a multi-institutional study, 735 patients with CRC were assigned to a retrospective training set (n = 420) or prospective validation set (n = 315). CTCs that expressed carcinoembryonic antigen (CEA), cytokeratin (CK) 19, CK20, and/or CD133 (CEA/CK/CD133) mRNA in PB were detected using real-time reverse transcription polymerase chain reaction assay. Results In the training sets, OS and DFS of patients who were positive for CEA/CK/CD133 were significantly worse than those of patients who were negative for these markers (P < .001). At each staging analysis, OS and DFS of patients with Dukes' stage B or C cancer who were positive for CEA/CK/CD133 were significantly worse than those of patients who were negative for these markers (P < .003 and P < .001 in Dukes' stage B; P < .001 in Dukes' stage C). In contrast, in patients with Dukes' stage A, no significant differences were seen between patients who were positive for these markers and those who were negative. Cox multivariate analysis demonstrated that CEA/CK/CD133 was a significant prognostic factor for OS (hazard ratio [HR], 3.84; 95% CI, 2.41 to 6.22; P < .001) and DFS (HR, 3.02; 95% CI, 1.83 to 5.00; P < .001). In particular, in patients with Dukes' stage B and C cancer, CEA/CK/CD133 demonstrated significant prognostic value. In validation sets, similar results were confirmed in patients with Dukes' stage B and C cancer. Conclusion In patients with Dukes' stage B and C CRC who require adjuvant chemotherapy, detection of CEA/CK/CD133 mRNA in PB is a useful tool for determining which patients are at high risk for recurrence and poor prognosis.

2020 ◽  
Wei Chen ◽  
Jun-Wen Ye ◽  
Xiao-ping Tan ◽  
Yan Zhang ◽  
Jing-Lin Liang ◽  

Abstract Objective: To observe the factors related to survival and prognosis of patients with resectable stage T4 colorectal cancer. Methods : 148 patients with resectable stage T4 colorectal cancer who underwent surgery in the first Affiliated Hospital of Sun Yat-sen University between August, 1994 and December, 2005 were retrospectively analyzed. Univariate and multivariate analyses of associations between clinicopathological variables and survival were analyzed using the Cox regression model. Results: At the end of December of 2010 or death, the 5-year and 10 years OS rates were 49.0% and 32.2% respectively, the median OS was 25 months. The disease free survival rates (DFS) at 5 and 10 years were 44.2% and 30.3% respectively. In univariate analysis, patients with postoperative pathology lymph node metastasis was associated with the prognosis of patients with OS (all P< 0.01), postoperative adjuvant therapy failed to improve OS and DFS (P>0.05). Postoperative pathology lymph node metastasis was associated with DFS too (all P< 0.01). In multivariate analysis, postoperative pathology lymph node metastasis was independent factor affected OS and DFS in colorectal cancer patients. Conclusion: Postoperative prognosis of T4 colorectal cancer patients is poor, postoperative pathology lymph node positive was an independent factor affect OS and DFS.

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 880 ◽  
Debora Basile ◽  
Lorenzo Gerratana ◽  
Angela Buonadonna ◽  
Silvio Garattini ◽  
Tiziana Perin ◽  

Background: Bruton’s tyrosine kinase (BTK) is involved in the immune response and its deficiency impairs B cell maturation. We evaluated the expression of a novel BTK isoform, p65BTK, in colorectal cancer (CRC), to identify its impact on survival. Materials and Methods: This retrospective study evaluated 87 consecutive stage III CRC patients treated at the National Cancer Institute of Aviano (1999–2017). Multiple specimens were collected and analyzed for staining intensity and percentage of tumor cells positive for p65BTK. Prognostic impact was tested by univariate Cox regression analysis. Results: After a median follow-up of 82.59 months, median disease-free survival (DFS) and overall survival (OS) were 11.67 months and 31.33 months, respectively. Interestingly, 10% of patients did not express p65BTK. For the immunohistochemistry IHC intensity 1, the best cutoff point was 1% of p65BTK positivity; for IHC intensity 2, it was 50%; and for IHC intensity 3, it was 80%. Through univariate analysis, patients with highly expressed p65BTK (IHC intensity 3 and ≥80%) were shown to have the worst prognosis in terms of DFS (HR: 6.23; p = 0.005; 95% C.I. 1.75–22.79) and OS (HR: 2.54; p = 0.025; 95% C.I. 1.12–5.76). Conclusions: p65BTK is frequently expressed in CRC and, if highly expressed, is an unfavourable prognostic factor. However, further confirmation is needed and its potential targeting needs to be studied.

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Takuya Shiraishi ◽  
Koji Ikeda ◽  
Yuichiro Tsukada ◽  
Yuji Nishizawa ◽  
Takeshi Sasaki ◽  

Abstract Background Transmembrane protein 180 (TMEM180) is a newly identified colorectal cancer (CRC)-specific molecule that is expressed very rarely in normal tissue and up-regulated under hypoxic conditions. We developed a monoclonal antibody (mAb) against TMEM180 and decided to examine the medical significance using the mAb. Methods A total of 157 patients (86 men and 71 women; median age 63.0 years) with stage III CRC who underwent curative surgery were analyzed for TMEM180 expression as a retrospective cohort design. Immunohistochemistry with anti-TMEM180 mAb was conducted on frozen sections, and the data were evaluated for any correlation with clinicopathological indices or prognosis. SW480 CRC cells were examined to investigate the relationship between the expression of TMEM180 and tumourigenesis of xenografts. Results In total, 92 cases had low TMEM expression and 65 had high TMEM180 expression. For disease-free survival, hazard ratio in high-TMEM180 cases was 1.449 (95% confidential interval = 0.802–2.619) higher than in low-TMEM180 cases, but the difference was not significant (p = 0.219). For cancer specific survival, hazard ratio in high-TMEM180 cases was 3.302 (95% confidential interval = 1.088–10.020), significantly higher than in low-TMEM180 cases (p = 0.035). In an assay examining in vitro colony-forming activity in soft agar, SW480-WT cells clearly formed colonies, but neither KD1 nor KD2 cells did. The in vivo tumour-initiating activity of SW480 cell lines was positively correlated with the level of TMEM180 expression. Conclusion These results indicate that TMEM180 is a useful marker for clinical prognosis in patients with CRC. We believe that these fundamental data warrant further basic and translational studies of TMEM180, and its mAb, for development of therapeutics against CRC.

2020 ◽  
Vol 14 (12) ◽  
pp. 1127-1137
Tong-Tong Zhang ◽  
Yi-Qing Zhu ◽  
Hong-Qing Cai ◽  
Jun-Wen Zheng ◽  
Jia-Jie Hao ◽  

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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