Association of Kras mutation with tumor deposit status and overall survival of colorectal cancer

AbstractBackgroundThe recent staging manual upstages Node-negative tumor-deposit positive colorectal cancer (CRC) from N0 to N1c category, while the development of tumor-deposit presence is poorly understood. Meanwhile, Kras mutation is associated with progression of CRC, but its link to tumor-deposit status is unclear.MethodThis retrospective cohort study included the patients with incidental CRC diagnosed during 2010-2014 in the National Cancer Database and recorded statuses of Kras and tumor deposit. We conducted multivariable logistic regression and Cox regression analyses to investigate the factors associated with tumor-deposit status and overall-survival, respectively.ResultsA total of 48,200 CRC patients with Kras status were included in the study (25,407 [52.7%] men, 25,648[46.8%] <65 years old, 18 381 [38.1%] with Kras mutation). Adjusted for microsatellite instability, age, pathologic stage and tumor grade, Kras mutation (versus wild-type) was associated with tumor-deposit presence (n=15,229, odds ratio=1.11, 95% CI 1.02 to 1.20). Kras mutation was also independently linked to a worse overall survival of CRC patients regardless of tumor-deposit status (n=8,110, adjusted Hazard ratio=1.40, 95% CI 1.09 to 1.79 for CRC with tumor deposits, and n=2,618, adjusted HR=1.63, 95% CI 1.16 to 2.28 for CRC without), but a better survival in CRC with no known/applicable tumor-deposit status (n=457, adjusted Hazard ratio =0.32, 95% CI 0.11 to 0.95).ConclusionKras mutation is independently associated with tumor-deposit presence, and a worse overall survival of CRC with or without tumor-deposit. Therefore, it may play a role in the development of tumor deposits and serve as a target for CRC treatment.

Download Full-text

Association of KRAS mutation with tumor deposit status and overall survival of colorectal cancer

Cancer Causes & Control ◽

10.1007/s10552-020-01313-0 ◽

2020 ◽

Vol 31 (7) ◽

pp. 683-689 ◽

Cited By ~ 1

Author(s):

Meifang Zhang ◽

Wenwei Hu ◽

Kun Hu ◽

Yong Lin ◽

Zhaohui Feng ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Kras Mutation ◽

Tumor Deposit

Download Full-text

Development and Validation of a Unique Gignature of Cancer Stemness-related Genes for Predicting the Overall survival of Colorectal Cancer Patients

10.21203/rs.3.rs-125323/v1 ◽

2020 ◽

Author(s):

Ran Wei ◽

Jichuan Quan ◽

Shuofeng Li ◽

Zhao Lu ◽

Xu Guan ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Cox Regression ◽

The Cancer Genome Atlas ◽

Cancer Stemness ◽

Poor Overall Survival ◽

Tissue Samples ◽

Cox Regression Analysis ◽

Rna Methylation ◽

M6a Rna Methylation

Abstract Background: Cancer stem cells (CSCs), which are characterized by self-renewal and plasticity, are highly correlated with tumor metastasis and drug resistance. To fully understand the role of CSCs in colorectal cancer (CRC), we evaluated the stemness traits and prognostic value of stemness-related genes in CRC.Methods: In this study, the data from 616 CRC patients from The Cancer Genome Atlas (TCGA) were assessed and subtyped based on the mRNA expression-based stemness index (mRNAsi). The correlations of cancer stemness with the immune microenvironment, tumor mutational burden (TMB) and N6-methyladenosine (m6A) RNA methylation regulators were analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to identify the crucial stemness-related genes and modules. Furthermore, a prognostic expression signature was constructed using Lasso-penalized Cox regression analysis. The signature was validated via multiplex immunofluorescence staining of tissue samples in an independent cohort of 48 CRC patients.Results: This study suggests that high mRNAsi scores are associated with poor overall survival in stage Ⅳ CRC patients. Moreover, the levels of TMB and m6A RNA methylation regulators were positively correlated with mRNAsi scores, and low mRNAsi scores were characterized by increased immune activity in CRC. The analysis identified 2 key modules and 34 key genes as prognosis-related candidate biomarkers. Finally, a 3-gene prognostic signature (PARPBP, KNSTRN and KIF2C) was explored together with specific clinical features to construct a nomogram, which was successfully validated in an external cohort. Conclusions: There is a unique correlation between CSCs and the prognosis of CRC patients, and the novel biomarkers related to cell stemness could accurately predict the clinical outcomes of these patients.

Download Full-text

Do Children With Constipation Have Increased Risk of Asthma? Real-World Data From a Nationwide Population-Based Cohort Study

Frontiers in Pediatrics ◽

10.3389/fped.2021.714406 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yen-Chu Huang ◽

Meng-Che Wu ◽

Yu-Hsun Wang ◽

James Cheng-Chung Wei

Keyword(s):

Cohort Study ◽

Cox Regression ◽

Population Based ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Research Database ◽

Real World Data ◽

Childhood Disorders ◽

Cox Regression Analysis ◽

Increased Risk

Background: Asthma is one of the most burdensome childhood disorders. Growing evidence disclose intestinal dysbiosis may contribute to asthma via the gut-lung axis. Constipation can lead to alteration of the gut microbiota. The clinical impact of constipation on asthma has not been researched. Therefore, we aim to assess whether pediatric constipation influence the risk of developing asthma by a nationwide population-based cohort study.Methods: We analyzed 10,363 constipated patients and 10,363 individuals without constipation between 1999 and 2013 from Taiwan's National Health Insurance Research Database. Analysis of propensity score was utilized to match age, sex, comorbidities, and medications at a ratio of 1:1. In addition, multiple Cox regression analysis was performed to evaluate the adjusted hazard ratio of asthma. Furthermore, sensitivity tests and a stratified analysis were performed.Results: After adjustment for age, sex, comorbidities, and medications, constipated patients had a 2.36-fold greater risk of asthma compared to those without constipation [adjusted hazard ratio (aHR): 2.36, 95% C.I. 2.04–2.73, p < 0.001]. Furthermore, the severity of constipation is associated with an increased risk of asthma; the adjusted hazard ratio was 2.25, 2.85, and 3.44 within < 3, 3–12, and ≥12 times of laxatives prescription within 1 year, respectively (p < 0.001).Conclusion: Constipation was correlated with a significantly increased risk of asthma. Pediatricians should be aware of the possibility of asthma in constipated patients. Further research is warranted to investigate the possible pathological mechanisms of this association.

Download Full-text

IMPACT OF KRAS MUTATIONS IN CLINICAL FEATURES IN COLORECTAL CANCER

ABCD Arquivos Brasileiros de Cirurgia Digestiva (São Paulo) ◽

10.1590/0102-672020200003e1524 ◽

2020 ◽

Vol 33 (3) ◽

Author(s):

Renato Morato ZANATTO ◽

Gianni SANTOS ◽

Júnea Caris OLIVEIRA ◽

Eduardo Marcucci PRACUCHO ◽

Adauto José Ferreira NUNES ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Kras Mutation ◽

Direct Sequencing ◽

Colorectal Carcinogenesis ◽

Kras Mutations ◽

Primary Tumor Site ◽

Exon 2 ◽

Metastatic Site ◽

Colorectal Cancer Patients

ABSTRACT Background: KRAS mutations are important events in colorectal carcinogenesis, as well as negative predictors of response to EGFR inhibitors treatment. Aim: To investigate the association of clinical-pathological features with KRAS mutations in colorectal cancer patients treated. Methods: Data from 69 patients with colorectal cancer either metastatic at diagnosis or later, were retrospectively analyzed. The direct sequencing and pyrosequencing techniques were related to KRAS exon 2. The mutation diagnosis and its type were determined. Results: KRAS mutation was identified in 43.4% of patients. The most common was c.35G>T (p.G12V), c.35G>A (p.G12D) and c.38G>A (p.G13D). No correlation was found between KRAS mutation and age (p=0.646) or gender (p=0.815). However, mutated group had higher CEA levels at admission (p=0.048) and codon 13 mutation was associated with involvement of more than one metastatic site in disease progression (p=0.029). Although there was no association between primary tumor site and mutation diagnosis (p=0.568), primary colon was associated with worse overall survival (p=0.009). Conclusion: The KRAS mutation was identified in almost half of patients. Mutated KRAS group had higher levels of CEA at admission and the mutation at codon 13 was associated with involvement of more than one metastatic site in the course of the disease. Colon disease was associated with the worst overall survival.

Download Full-text

A grading system for predicting the prognosis of gastric cancer with liver metastasis

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyab140 ◽

2021 ◽

Author(s):

Soshi Hori ◽

Michitaka Honda ◽

Hiroshi Kobayashi ◽

Hidetaka Kawamura ◽

Koichi Takiguchi ◽

...

Keyword(s):

Colorectal Cancer ◽

Gastric Cancer ◽

Overall Survival ◽

Liver Metastasis ◽

Confidence Interval ◽

Liver Metastases ◽

Hazard Ratio ◽

Maximum Diameter ◽

Grading System ◽

Computed Tomography Images

Abstract Objective The prognosis of patients with liver metastases from gastric cancer is determined using tumor size and number of metastases; this is similar to the factors used for the prediction of liver metastases from colorectal cancer. The relationship between the degree of liver metastasis from gastric cancer and prognosis with reference to the classification of liver metastasis from colorectal cancer was investigated. Methods This was a multi-institutional historical cohort study. Among patients with stage IV gastric cancer, who visited the cancer hospitals in Fukushima Prefecture, Japan, between 2008 and 2015, those with simultaneous liver metastasis were included. Abdominal pretreatment computed tomography images were reviewed and classified into H1 (four or less liver metastases with a maximum diameter of ≤5 cm); H2 (other than H1 and H3) or H3 (five or more liver metastases with a maximum diameter of ≥5 cm). The hazard ratio for overall survival according to the H grade (H1, H2 and H3) was calculated using the Cox proportional hazards model. Results A total of 412 patients were analyzed. Patients with H1, H2 and H3 grades were 118, 162 and 141, respectively, and their median survival time was 10.2, 5.7 and 3.1 months, respectively (log-rank P < 0.001). The adjusted hazard ratio for overall survival was H1: H2: H3 = reference: 1.39 (95% confidence interval: 1.04–1.85): 1.69 (95% confidence interval: 1.27–2.27). Conclusions The grading system proposed in this study was a simple and easy-to-use prognosis prediction index for patients with liver metastasis from gastric cancer.

Download Full-text

Determinants of hospitalizations for pneumonia among Finnish drug users

SAGE Open Medicine ◽

10.1177/2050312118784311 ◽

2018 ◽

Vol 6 ◽

pp. 205031211878431 ◽

Cited By ~ 3

Author(s):

Olubunmi O Olubamwo ◽

Ifeoma N Onyeka ◽

Alex Aregbesola ◽

Kimmo Ronkainen ◽

Jari Tiihonen ◽

...

Keyword(s):

Drug Use ◽

Confidence Interval ◽

Drug Users ◽

Cox Regression ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Intravenous Drug ◽

Intravenous Drug Use ◽

Cox Models ◽

Clinical Consultation

Objective: The study examined the determinants of being hospitalized for pneumonia in a large cohort of drug users. Methods: Information of 4817 clients seeking treatment for illicit drug use was linked with the Finnish hospital discharge register to identify those who were hospitalized with main/primary diagnoses of pneumonia during 1997–2013. Cox regression models were used to examine the association between age, gender, homelessness, and route of drug administration of the primary drug at initial clinical consultation and pneumonia hospitalization. Findings were presented as adjusted hazard ratios and 95% confidence intervals. Results: There were 354 persons diagnosed with pneumonia, with a total of 522 hospitalizations at the end of 2013. The univariate Cox models revealed that being over 44 years of age, male gender, homelessness, and intravenous drug use at initial clinical consultation increased the risk of being hospitalized for pneumonia. In the fully adjusted multivariate model, being over 44 years was the strongest factor independently associated with pneumonia hospitalization (adjusted hazard ratio: 2.67, 95% confidence interval: 1.56–4.57, p < 0.001), followed by homelessness (adjusted hazard ratio: 1.75, 95% confidence interval: 1.38–2.22, p < 0.001) and intravenous drug use (adjusted hazard ratio: 1.27, 95% confidence interval: 1.01–1.59, p = 0.041). Of the 354 clients hospitalized for pneumonia, 31.9% ( n = 113) were rehospitalized within 30 days of being discharged. One-third of the reasons for the 30-day rehospitalization were pneumonia-related. Conclusion: Vaccination, measures addressing housing instability, safe injecting and good hygienic practices, and treating underlying drug use problems could help to reduce morbidity for pneumonia in this cohort.

Download Full-text

Clinicopathological and molecular differences in colorectal cancer according to location

The International Journal of Biological Markers ◽

10.1177/1724600818807164 ◽

2019 ◽

Vol 34 (1) ◽

pp. 47-53 ◽

Cited By ~ 5

Author(s):

Yu-Lun Hsu ◽

Chun-Chi Lin ◽

Jeng-Kai Jiang ◽

Hung-Hsin Lin ◽

Yuan-Tzu Lan ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Overall Survival ◽

Cox Regression ◽

Rank Test ◽

Advanced Tumor Stage ◽

Tumor Seeding ◽

Cox Regression Analysis ◽

Advanced Tumor ◽

Tumor Node Metastasis Stage

Purpose: The incidence, pathogenesis, molecular pathways, and outcomes of colorectal cancer vary depending on the location of the tumor. This study aimed to compare the difference in tumor characteristics and the outcome between right-sided colon cancer and left-sided colorectal cancer (LCRC). Materials and methods: A total of 1503 patients with colorectal cancer who underwent surgery at the Taipei Veterans General Hospital between 2000 and 2010 were enrolled in this study. Right-sided colon cancer was defined as cancers in the cecum, ascending colon, and transverse colon, while LCRC was defined as cancers in the splenic flexure colon, descending colon, sigmoid colon, and rectum. The endpoint was overall survival. The mutations were detected via polymerase chain reaction and MASS array. The prognostic value was determined using the log-rank test and the Cox regression analysis. Results: A total of 407 and 1096 cases were classified as right-sided colon cancer and LCRC, respectively. Compared to patients with LCRC, those with right-sided colon cancer had more mucinous type cancer (7.4% vs. 3.5%), poorly differentiated tumor (11.5% vs. 3.6%), and advanced tumor-node-metastasis stage. The risk for peritoneal tumor seeding was higher in the right-sided colon cancer group (12.8% vs. 5.7%). Overall survival was better in LCRC than in right-sided colon cancer ( P=0.036). Conclusions: In our study, right-sided colon cancer had a more advanced tumor stage, a higher risk of peritoneal metastasis, and a poorer outcome than LCRC. Moreover, right-sided colon cancer had more gene mutations in BRAF, KRAS, SMAD4, TGF-β, PIK3CA, PTEN, AKT1, and high microsatellite instability.

Download Full-text

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.

Download Full-text

Prognostic roles of microRNA 143 and microRNA 145 in colorectal cancer: A meta-analysis

The International Journal of Biological Markers ◽

10.1177/1724600818807492 ◽

2019 ◽

Vol 34 (1) ◽

pp. 6-14 ◽

Cited By ~ 4

Author(s):

Chenyao Li ◽

Guoqiang Yan ◽

Libin Yin ◽

Tao Liu ◽

Chao Li ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Hazard Ratio ◽

High Expression ◽

Cochrane Library ◽

Event Free Survival ◽

Free Survival ◽

High Event ◽

Low Expression

Background: A systematic analysis was conducted to clarify the relationship between miR-143/145 and the prognosis of colorectal cancer. Materials and methods: We searched four databases: PubMed, EMBASE, Web of Science, and the Cochrane Library. We extracted and estimated the hazard ratios for survival outcomes, which compared low and high expression levels of miR-143/145 in colorectal cancer patients in the available studies. Each individual hazard ratio was used to calculate the pooled hazard ratio. Results: A total of 17 articles including 5128 patients were ultimately included. The results showed that there was no significant difference between low expression and high expression of miR-143 in the overall survival of colon cancer patients. However, low expression of miR-143 was significantly associated with high event-free survival (hazard ratio (HR) 0.6; 95% confidence interval (CI) 0.40, 0.88). Low expression of miR-145 was associated with poor prognosis of patients (HR 1.92; 95% CI 1.45, 2.54); those with low expression of miR-145 were at 1.92-fold higher risk for short-term overall survival than those with high expression of miR-145. MiR-145 was an unfavorable factor for the prognosis of colorectal cancer. There were no significant differences between low expression of miR-145 and high expression of miR-143 in event-free survival. Conclusion: miR-143 and miR-145 have promising prognostic value for colorectal cancer. Low expression of miR-143 can predict high event-free survival, and low expression of miR-145 can predict poor overall survival.

Download Full-text

Adjuvant Chemotherapy After Potentially Curative Resection of Metastases From Colorectal Cancer: A Pooled Analysis of Two Randomized Trials

Journal of Clinical Oncology ◽

10.1200/jco.2008.17.3781 ◽

2008 ◽

Vol 26 (30) ◽

pp. 4906-4911 ◽

Cited By ~ 360

Author(s):

Emmanuel Mitry ◽

Anthony L.A. Fields ◽

Harry Bleiberg ◽

Roberto Labianca ◽

Guillaume Portier ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Adjuvant Chemotherapy ◽

Progression Free Survival ◽

Pooled Analysis ◽

Complete Resection ◽

Hazard Ratio ◽

Free Survival ◽

Cancer Metastases ◽

Colorectal Cancer Metastases

Purpose Adjuvant systemic chemotherapy administered after surgical resection of colorectal cancer metastases may reduce the risk of recurrence and improve survival, but its benefit has never been demonstrated. Two phase III trials (Fédération Francophone de Cancérologie Digestive [FFCD] Trial 9002 and the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada Clinical Trials Group/Gruppo Italiano di Valutazione Interventi in Oncologia [ENG] trial) used a similar design and showed a trend favoring adjuvant chemotherapy, but both had to close prematurely because of slow accrual, thus lacking the statistical power to demonstrate the predefined difference in survival. We report here a pooled analysis based on individual data from these two trials. Patients and Methods After complete resection of colorectal liver or lung metastases, patients were randomly assigned to chemotherapy (CT arm; fluorouracil [FU] 400 mg/m2 administered intravenously [IV] once daily plus dl-leucovorin 200 mg/m2 [FFCD] × 5 days or FU 370 mg/m2 plus l-leucovorin 100 mg/m2 IV × 5 days [ENG] for six cycles at 28-day intervals) or to surgery alone (S arm). Results A total of 278 patients (CT, n = 138; S, n = 140) were included in the pooled analysis. Median progression-free survival was 27.9 months in the CT arm as compared with 18.8 months in the S arm (hazard ratio = 1.32; 95% CI, 1.00 to 1.76; P = .058). Median overall survival was 62.2 months in the CT arm compared with 47.3 months in the S arm (hazard ratio = 1.32; 95% CI, 0.95 to 1.82; P = .095). Adjuvant chemotherapy was independently associated with both progression-free survival and overall survival in multivariable analysis. Conclusion This pooled analysis shows a marginal statistical significance in favor of adjuvant chemotherapy with an FU bolus–based regimen after complete resection of colorectal cancer metastases.

Download Full-text