Blood cholesterol-to-lymphocyte ratio as a novel prognostic marker to predict postoperative overall survival in patients with colorectal cancer

Abstract Background Lipid disequilibrium and systemic inflammation are reported to correlate with tumorigenesis and development of colorectal cancer (CRC). We construct the novel biomarker cholesterol-to-lymphocyte ratio (CLR) to reflect the synergistic effect of cholesterol metabolism and inflammation on CRC outcomes. This study aims to investigate the clinical significance of CLR and establish a prognostic model for CRC. Methods Our study retrospectively enrolled 223 CRC patients who underwent curative surgical resection. The Kaplan-Meier method was employed to estimate the overall survival (OS) rates, and the association between serological biomarkers and survival was assessed with a log-rank test. Cox proportional hazard regression was applied in the univariate and multivariate analyses to identify independent prognostic factors, which were then used to develop a predictive nomogram model for OS in CRC. The nomogram was evaluated by the C-index, receiver operator characteristic curve (ROC) analysis, and calibration plot. All cases were grouped into three stratifications according to the total risk points calculated from the nomogram, and the difference in OS between them was assessed with the Kaplan-Meier method. Results At the end of the study, death occurred in 47 (21%) cases. Patients with low CLR (< 3.23) had significantly prolonged survival (P < 0.001). Multivariate analyses revealed that N stage (P < 0.001), harvested lymph nodes (P = 0.021), and CLR (P = 0.005) were independent prognostic factors for OS and a prognostic nomogram was established based on these variables. The nomogram showed good calibration and predictive performance with a superior C-index than TNM stage (0.755 (0.719–0.791) vs. 0.663 (0.629–0.697), P = 0.001). Patients of different risk stratifications based on the total score of nomogram showed distinct survival (P < 0.001). Conclusions The nomogram based on CLR and other clinical features can be used as a potentially convenient and reliable tool in predicting survival in patients with CRC.

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Outcomes of Surgical and Nonsurgical Treatment for Colorectal Cancer in Nonagenarian Patients

The American Surgeon ◽

10.1177/0003134821995060 ◽

2021 ◽

pp. 000313482199506

Author(s):

Youngbae Jeon ◽

Kyoung-Won Han ◽

Won-Suk Lee ◽

Jeong-Heum Baek

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Surgical Treatment ◽

Postoperative Complications ◽

Postoperative Mortality ◽

Nonsurgical Treatment ◽

Perioperative Outcomes ◽

Rank Test ◽

Kaplan Meier ◽

Number Of Patients

Purpose This study is aimed to evaluate the clinical outcomes of surgical treatment for nonagenarian patients with colorectal cancer. Methods This retrospective single-center study included patients diagnosed with colorectal cancer at the age of ≥90 years between 2004 and 2018. Patient demographics were compared between the operation and nonoperation groups (NOG). Perioperative outcomes, histopathological outcomes, and postoperative complications were evaluated. Overall survival was analyzed using Kaplan-Meier methods and log-rank test. Results A total of 31 patients were included (16 men and 15 women), and the median age was 91 (range: 90‐96) years. The number of patients who underwent surgery and who received nonoperative management was 20 and 11, respectively. No statistical differences in baseline demographics were observed between both groups. None of these patients were treated with perioperative chemotherapy or radiotherapy. Surgery comprised 18 (90.0%) colectomies and 2 (10.0%) transanal excisions. Short-term (≤30 days) and long-term (31‐90 days) postoperative complications occurred in 7 (35.0%) and 4 (20.0%) patients, respectively. No complications needed reoperation, such as anastomosis leakage or bleeding. No postoperative mortality occurred within 30 days: 90-day postoperative mortality occurred in two patients (10.0%), respectively. The median overall survival of the operation group was 31.6 (95% confidence interval: 26.7‐36.5) and that of NOG was 12.5 months (95% CI: 2.4‐22.6) ( P = 0.012). Conclusion Surgical treatment can be considered in carefully selected nonagenarian patients with colorectal cancer in terms of acceptable postoperative morbidity, with better overall survival than the nonsurgical treatment.

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Factors associated with the survival of colorectal cancer in Mexico

Intestinal Research ◽

10.5217/ir.2019.09179 ◽

2020 ◽

Vol 18 (3) ◽

pp. 315-324 ◽

Cited By ~ 1

Author(s):

Carlos Quezada-Gutiérrez ◽

María Teresa Álvarez-Bañuelos ◽

Jaime Morales-Romero ◽

Clara Luz Sampieri ◽

Raúl Enrique Guzmán-García ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Factors ◽

Cox Regression ◽

Clinical Stage ◽

Public Health Problem ◽

Rank Test ◽

Cancer Center ◽

Advanced Clinical Stage ◽

Probability Of Survival ◽

Kaplan Meier

Background/Aims: Colorectal cancer (CRC) is a public health problem. In Mexico, there have been no recent studies conducted on survival in terms of this pathology or on the influence of prognostic factors. The study aims to determine the probability of survival in patients with CRC presence of low levels of schooling and a rural population, adjusted for clinical stage and type of treatment.Methods: A retrospective study was conducted in a cohort of 305 patients with CRC treated at State Cancer Center, located in Veracruz-Mexico; the follow-up period of 60 months (2012–2016). The survival probability was calculated using the Kaplan-Meier estimator and the log-rank test with 95% confidence intervals (CIs). Prognostic factors were determined using hazard ratio (HR) multivariate Cox regression analysis.Results: Overall survival was 40% at 60 months. Subjects in the age group ≥ 65 years had a low survival rate of 28% (P= 0.026) and an advanced clinical stage of 22% (P< 0.001). Of the patients with bone metastasis, none survived longer than 5 years (P= 0.008). With respect to the unfavorable prognostic factors identified in the multivariate analysis, a decreased level of schooling was associated with an HR of 7.6 (95% CI, 1.1–54.7), advanced clinical stage was associated with an HR of 2.1 (95% CI, 1.2–4.0), and the presence of metastasis had an HR of 1.8 (95% CI, 1.1–2.9).Conclusions: Poor prognostic factors include an advanced clinical stage, the presence of metastasis and a low level of schooling. These findings confirm the importance of screening for early diagnosis, diminishing the barriers to accessing treatment and prospectively monitoring the population.

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PGM5 is a promising biomarker and may predict the prognosis of colorectal cancer patients

Cancer Cell International ◽

10.1186/s12935-019-0967-y ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 7

Author(s):

Yifan Sun ◽

Haihua Long ◽

Lin Sun ◽

Xiujuan Sun ◽

Liping Pang ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Cox Regression ◽

Migration And Invasion ◽

Rank Test ◽

Poor Overall Survival ◽

Tissue Samples ◽

Invasion And Migration ◽

Kaplan Meier ◽

And Migration

Abstract Background Phosphoglucomutase (PGM), a key enzyme in the metabolism of glucose-1-phosphate and glucose-6-phosphate, has been found to be associated with proliferation, invasion, and metastasis of cancer. However, the expression and function of PGM5 in colorectal cancer (CRC) remains unknown. Methods We tested PGM5 mRNA and protein expression levels in 79 CRC tissue and their matched adjacent tissue samples by qRT-PCR and immunohistochemistry, respectively. Overall survival (OS) was estimated with the Kaplan–Meier method and compared between groups with the log-rank test. We performed multivariable Cox regression analyses to identify factors associated with CRC risk. The cell proliferation, migration and invasion abilities of CRC cells were detected by using CCK-8, Transwell migration and invasion assays, respectively. Results The PGM5 protein levels expression in CRC tissues were significantly lower than those in the adjacent tissues (t = 5.035, P < 0.001), and Kaplan–Meier analysis indicated that low PGM5 expression were significantly associated with poor overall survival (P = 0.0069). Univariate and multivariate analyses demonstrated that PGM5 was an independent risk factor for overall survival (hazard ratio = 0.3951, P = 0.014). PGM5 overexpression significantly inhibited the proliferation, invasion and migration abilities of CRC cells. On the contrary, knockdown of PGM5 promotes the invasion and migration of CRC cells. Conclusions PMG5 regulates proliferation, invasion, and migration in the CRC and decreased PGM5 is associated with poor prognosis. Therefore, PGM5 is a promising biomarker in CRC and decreased PGM5 may predict poor overall survival in patients with CRC.

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Relationship of common variants in Krüppel-like factor 7 gene with susceptibility and prognosis of oral squamous cell carcinoma

10.21203/rs.3.rs-61631/v1 ◽

2020 ◽

Author(s):

Lili Wang ◽

Hongguang Song ◽

Shiming Yang

Keyword(s):

Overall Survival ◽

Squamous Cell Carcinoma ◽

Prognostic Factor ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Multivariate Analyses ◽

Rank Test ◽

Log Rank Test ◽

Kaplan Meier ◽

Tumor Tissues

Abstract Background The aim of this study was to assess the prognostic value of Krüppel-like factor 7 (KLF7) for patients with oral squamous cell carcinoma(OSCC). Methods The expression of KLF7 was detected by quantitative real-time polymerase chain reaction (qRT-PCR) in pairs of tumor tissues and adjacent non-tumor tissues of OSCC. Chi-square (χ2) test was applied to evaluate the association of KLF7 expression with clinicopathological characteristics of OSCC patients. Overall survival was estimated using the Kaplan-Meier method with log rank test. The cox proportional hazards model was used for univariate and multivariate analyses. Results The expression of KLF7 was remarkably increased in OSCC tissues compared with adjacent non-tumor tissues (P < 0.001). KLF7 expression was related to TNM stage (P = 0.006), tumor size (P = 0.010), smoking (P = 0.006) and drinking (P = 0.000). Kaplan-Meier analysis showed that OSCC patients with high KLF7 expression had a poorer overall survival than those with low expression (log rank test, P = 0.018). Moreover, multivariate analyses showed that KLF7 was an independent prognostic factor for OSCC (P = 0.002 HR = 2.645 95%CI: 1.426–4.906). Conclusion Decreased expression of KLF7 may be a potential unfavorable prognostic factor for patients with OSCC.

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Relationship of Common Variants in Krüppel-like Factor 7 Gene With Susceptibility and Prognosis of Oral Squamous Cell Carcinoma

10.21203/rs.3.rs-48539/v1 ◽

2020 ◽

Author(s):

Lili Wang ◽

Hongguang Song ◽

Shiming Yang

Keyword(s):

Overall Survival ◽

Squamous Cell Carcinoma ◽

Prognostic Factor ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Multivariate Analyses ◽

Rank Test ◽

Log Rank Test ◽

Kaplan Meier ◽

Tumor Tissues

Abstract Background: The aim of this study was to assess the prognostic value of Krüppel-like factor 7 (KLF7) for patients with oral squamous cell carcinoma(OSCC).Methods: The expression of KLF7 was detected by quantitative real-time polymerase chain reaction (qRT-PCR) in pairs of tumor tissues and adjacent non-tumor tissues of OSCC. Chi-square (χ2) test was applied to evaluate the association of KLF7 expression with clinicopathological characteristics of OSCC patients. Overall survival was estimated using the Kaplan-Meier method with log rank test. The cox proportional hazards model was used for univariate and multivariate analyses.Results: The expression of KLF7 was remarkably increased in OSCC tissues compared with adjacent non-tumor tissues (P<0.001). KLF7 expression was related to TNM stage (P=0.006), tumor size (P=0.010), smoking (P=0.006) and drinking (P=0.000). Kaplan-Meier analysis showed that OSCC patients with high KLF7 expression had a poorer overall survival than those with low expression (log rank test, P=0.018). Moreover, multivariate analyses showed that KLF7 was an independent prognostic factor for OSCC (P=0.002 HR=2.645 95%CI: 1.426-4.906).Conclusion: Decreased expression of KLF7 may be a potential unfavorable prognostic factor for patients with OSCC.

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Clinicopathologic Features and Prognostic Factors in Alpha-Fetoprotein-Producing Colorectal Cancer: Analysis of 78 Cases

Cellular Physiology and Biochemistry ◽

10.1159/000495824 ◽

2018 ◽

Vol 51 (5) ◽

pp. 2052-2064 ◽

Cited By ~ 2

Author(s):

Yang Feng ◽

Yaqi Li ◽

Weixing Dai ◽

Shaobo Mo ◽

Qingguo Li ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Prognostic Factors ◽

Liver Metastasis ◽

Multivariable Analysis ◽

Elevated Serum ◽

Alpha Fetoprotein ◽

Rank Test ◽

Cancer Center ◽

Clinicopathologic Characteristics

Background/Aims: Alpha-fetoprotein-producing colorectal cancer (AFPP-CRC) is quite rarely seen. This study aimed to elucidate the clinicopathologic characteristics and prognostic factors of AFPP-CRC. Methods: Among 5,051 colorectal cancer patients receiving surgery in the Fudan University Shanghai Cancer Center from 2006 to 2016, we identified 78 patients with elevated serum level of AFP (> 10 µg/L) preoperatively. A propensity score matching (PSM) analysis was performed which matched 75 AFPP-CRC patients to the same number of AFP-negative colorectal cancer (AFPN-CRC) patients. Kaplan-Meier curves were compared using the log-rank test and multivariable analysis was performed to evaluate the effect of AFP-positivity while adjusting confounding factors. 27 patients were available for immunohistochemical analysis. We conducted functional experiments to characterize the tumorigenicity of AFP. Results: Patients with AFPP-CRC had a significantly higher incidence of advanced TNM stage and liver metastasis. Overall survival was significantly different between two groups before and after PSM, and AFP-positivity was one of the strongest predictors of overall survival in the multivariable model (HR 4.11, CI 95%: 1.43-11.76, p = 0.009) after PSM. We further investigated prognostic factors affecting prognosis in AFPP-CRC and found that the presence of liver metastasis was the only independent prognostic factor (HR 4.95, CI 95%: 1.48-16.48, p = 0.009). AFP expression was significantly positively correlated with HGF and c-Met expression. Transwell invasion assay revealed significantly increased cell motility with AFP overexpression. Conclusion: AFP-positivity is a significant negative predictor of overall survival in patients with colorectal cancer, which may be mediated by HGF/c-Met signaling pathway.

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Prognostic Nomograms based on Homogeneous and Heterogeneous Associated Factors for Predicting the Overall Survival of Colorectal Cancer Patients with Distant Metastases

10.21203/rs.3.rs-600814/v1 ◽

2021 ◽

Author(s):

Hongmei Wang ◽

Xuefeng Shan ◽

min zhang ◽

Kun Qian ◽

Weiying Zhou

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Prognostic Factors ◽

Cox Regression ◽

Lung Metastases ◽

Distant Metastases ◽

Calibration Curves ◽

Kaplan Meier ◽

Poor Differentiation ◽

Colorectal Cancer Patients

Abstract Background: To identify the heterogeneous and homogeneous prognostic factors associated with distant metastases in colorectal cancer (CRC) patients and then construct nomograms to predict prognosis.Methods: CRC patients registered in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016 were included. Cox regression was used to analyse homogeneous and heterogeneous prognostic factors, and Kaplan-Meier analysis was used to estimate overall survival (OS). Predictive nomograms were constructed, and their performance was evaluated with C-indexes and calibration curves.Results: A total of 34933 patients with distant metastases were included. The median survival time of patients with liver metastases, lung metastases, bone metastases, and brain metastases were 12.00 months (95% CI: 11.71-12.29 months), 10.00 months (95% CI: 9.57-10.43 months), 5.00 months (95% CI: 4.47-5.53 months), and 3.00 months (95% CI: 2.31-3.70 months), respectively. Older age and no surgery were identified as homogeneous prognostic factors of the four types of metastases. Male sex, black race, unmarried status, uninsured status, primary CRC site, poor differentiation/grade, advanced N stage, T stage, high carcinoembryonic antigen (CEA) level and metastatic organ were heterogeneously associated with the prognosis of patients with distant metastases. The calibration curves and C-indexes exhibited good performance for predicting the OS of patients with distant metastases.Conclusion: CRC patients with distant metastases exhibited homogeneous and heterogeneous prognostic factors, all of which were associated with poor survival. The nomograms showed good accuracy and can be used as tools for clinicians to predict the prognosis of CRC patients with distant metastases.

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IL15RA and SMAD3 Genetic Variants Predict Overall Survival in Metastatic Colorectal Cancer Patients Treated with FOLFIRI Therapy: A New Paradigm

Cancers ◽

10.3390/cancers13071705 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1705

Author(s):

Elena De Mattia ◽

Jerry Polesel ◽

Rossana Roncato ◽

Adrien Labriet ◽

Alessia Bignucolo ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Metastatic Colorectal Cancer ◽

Cancer Patients ◽

Prognostic Score ◽

Chemotherapeutic Agents ◽

Rank Test ◽

P Value ◽

Genetic Determinants ◽

New Paradigm

A new paradigm in cancer chemotherapy derives from the interaction between chemotherapeutics, including irinotecan and 5-fluorouracil (5-FU), and the immune system. The patient’s immune response can modulate chemotherapy effectiveness, and, on the other hand, chemotherapeutic agents can foster tumor cell immunogenicity. On these grounds, the analysis of the cancer patients’ immunogenetic characteristics and their effect on survival after chemotherapy represent a new frontier. This study aims to identify genetic determinants in the immuno-related pathways predictive of overall survival (OS) after FOLFIRI (irinotecan, 5-FU, leucovorin) therapy. Two independent cohorts comprising a total of 335 patients with metastatic colorectal cancer (mCRC) homogeneously treated with first-line FOLFIRI were included in the study. The prognostic effect of 192 tagging genetic polymorphisms in 34 immune-related genes was evaluated using the bead array technology. The IL15RA rs7910212-C allele was associated with worse OS in both discovery (HR: 1.57, p = 0.0327, Bootstrap p-value = 0.0280) and replication (HR:1.71, p = 0.0411) cohorts. Conversely, SMAD3 rs7179840-C allele was associated with better OS in both discovery (HR:0.65, p = 0.0202, Bootstrap p-value = 0.0203) and replication (HR:0.61, p = 0.0216) cohorts. A genetic prognostic score was generated integrating IL15RA-rs7910212 and SMAD3-rs7179840 markers with inflammation-related prognostic polymorphisms we previously identified in the same study population (i.e., PXR [NR1I2]-rs1054190, VDR-rs7299460). The calculated genetic score successfully discriminated patients with different survival probabilities (p < 0.0001 log-rank test). These findings provide new insight on the prognostic value of genetic determinants, such as IL15RA and SMAD3 markers, and could offer a new decision tool to improve the clinical management of patients with mCRC receiving FOLFIRI.

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Survival Outcomes for Induction vs Adjuvant Chemotherapy in Squamous Cell Carcinoma of the Maxillary Sinus

Otolaryngology ◽

10.1177/0194599818804777 ◽

2018 ◽

Vol 160 (4) ◽

pp. 658-663 ◽

Cited By ~ 4

Author(s):

Phoebe Kuo ◽

Sina J. Torabi ◽

Dennis Kraus ◽

Benjamin L. Judson

Keyword(s):

Overall Survival ◽

Adjuvant Chemotherapy ◽

Maxillary Sinus ◽

Induction Chemotherapy ◽

Squamous Cell ◽

Cox Regression ◽

Rank Test ◽

Controlled Clinical Trial ◽

Log Rank Test ◽

Kaplan Meier

Objective In advanced maxillary sinus cancers treated with surgery and radiotherapy, poor local control rates and the potential for organ preservation have prompted interest in the use of systemic therapy. Our objective was to present outcomes for induction compared to adjuvant chemotherapy in the maxillary sinus. Study Design Secondary database analysis. Setting National Cancer Database (NCDB). Subjects and Methods In total, 218 cases of squamous cell maxillary sinus cancer treated with surgery, radiation, and chemotherapy between 2004 and 2012 were identified from the NCDB and stratified into induction chemotherapy and adjuvant chemotherapy cohorts. Univariate Kaplan-Meier analyses were compared by log-rank test, and multivariate Cox regression was performed to evaluate overall survival when adjusting for other prognostic factors. Propensity score matching was also used for further comparison. Results Twenty-three patients received induction chemotherapy (10.6%) and 195 adjuvant chemotherapy (89.4%). The log-rank test comparing induction to adjuvant chemotherapy was not significant ( P = .076). In multivariate Cox regression when adjusting for age, sex, race, comorbidity, grade, insurance, and T/N stage, there was a significant mortality hazard ratio of 2.305 for adjuvant relative to induction chemotherapy (confidence interval, 1.076-4.937; P = .032). Conclusion Induction chemotherapy was associated with improved overall survival in comparison to adjuvant chemotherapy in a relatively small cohort of patients (in whom treatment choice cannot be characterized), suggesting that this question warrants further investigation in a controlled clinical trial before any recommendations are made.

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Prognostic value of preoperative inflammatory markers in patients with hepatocellular carcinoma underwent curative resection

10.21203/rs.3.rs-434954/v1 ◽

2021 ◽

Author(s):

Wenlong Wu ◽

Quancheng Wang ◽

Dandan Han ◽

Jianhui Li ◽

Ye Nie ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Prognostic Factors ◽

Inflammatory Markers ◽

Curative Resection ◽

Information Criterion ◽

Gamma Glutamyl Transpeptidase ◽

Roc Curve Analysis ◽

Lymphocyte Ratio ◽

Kaplan Meier ◽

Glutamyl Transpeptidase

Abstract Background: The prognosis of hepatocellular carcinoma (HCC) is not optimistic. Our study focused on present inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), gamma-glutamyl transpeptidase-to-platelet ratio (GPR), aspartate aminotransferase-to-lymphocyte ratio (ALR) and fibrinogen-to-albumin ratio (FAR), and aimed to explore their optimal combination for the prognosis of HCC after resection.Methods: 347 HCC patients with curative resection were enrolled. The optimal cutoff values of the inflammatory markers were calculated using receiver operating characteristic (ROC) curve analysis, and used to divide patients into two groups whose differences were compared by Kaplan-Meier analysis. Cox univariate and multivariate analysis were used to analyze the independent prognostic inflammatory markers. c2 test was chosen to determine the relationship between independent prognostic inflammatory markers and clinicopathological features. We created the combined scoring models and evaluated them by Cox univariate and multivariate methods. The concordance index (C-index), Akaike information criterion (AIC) and likelihood ratio were calculated to compare the models. The selected optimal inflammatory markers and their combinations were tested in different stages of HCC by Kaplan-Meier analysis.Results: ALR and GPR were independent prognostic factors for DFS; ALR, PLR, and GPR were independent prognostic factors for OS. The proposed GPR and ALR-GPR-PLR score models were independent predictors for DFS and OS, respectively.Conclusion: The preoperative GPR and ALR-GPR-PLR score models were independent predictors for DFS and OS, respectively, and performed well in stratifying patients with HCC. The higher score in the model, the worse the prognosis was.

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