scholarly journals Identifying miRNA Biomarkers and Predicted Targets Associated with Venous Thromboembolism in Colorectal Cancer Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3643-3643
Author(s):  
Ann S. Kim ◽  
Matthew F Kalady ◽  
Jennifer DeVecchio ◽  
Kahraman Tanriverdi ◽  
Jane E. Freedman ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Board Of Directors ◽  
Cancer Patients ◽  
Cancer Diagnosis ◽  
Target Genes ◽  
Differentially Expressed ◽  
Blood Collection ◽  
Advisory Committees ◽  
After Cancer ◽  
Colorectal Cancer Patients

Introduction Venous thromboembolism (VTE) is the second leading cause of mortality among cancer patients and is potentially preventable through the use of anticoagulation therapy. Risk models exist to guide use of prophylactic therapy but have low positive predictive value. New biomarkers are needed, particularly in intermediate-risk cancer types. Extracellular small RNAs, such as miRNAs, are promising biomarkers that have been implicated in tumor-dependent modification of platelets, a key component of thrombus formation. In this pilot study, we explore miRNAs as potential biomarkers for VTE risk in patients with colorectal cancer. Methods We conducted a case-control study utilizing specimens from a population enrolled in a prospective colorectal cancer biorepository at the Cleveland Clinic. Cases were defined as patients who developed VTE, including deep vein thrombosis and pulmonary embolism, within 6 months after cancer diagnosis and had their blood drawn prior to VTE. Cases were matched to controls (who did not have VTE and had a minimum of 6 months survival after cancer diagnosis) on a 1:2 ratio based on age, sex, cancer stage at diagnosis, and cancer treatment received prior to blood collection for a total of 21 patients. Total RNA from plasma specimens were sequenced on a Ion Proton platform (Thermo Fisher). Sequencing data were analyzed using the limma-voom R package. As this study was meant to be exploratory, miRNA were determined to be differentially expressed at a corrected Benjamini-Hochberg false detection rate (FDR) < 0.2. Target genes of differentially expressed miRNAs were predicted using mirDB and target gene pathways constructed with PANTHER. Results The study population had a median age of 65 (IQR 51-72). Of these patients, 85.7% were male; 42.9% had stage I/II cancer, 42.9% stage III cancer, 14.3% stage IV cancer; 71.4% had received no treatment prior to blood collection, 14.3% received chemo/chemoradiation therapy, and 14.3% received surgery. A total of 2426 unique miRNAs (median 1524, IQR 1371-1665) were expressed in the study group. Of these, 9 miRNAs were significantly differentially expressed (FDR < 0.2) and downregulated in cases compared to controls: hsa-miR-4451, 942-3p, 8063, 3132, 3118, 105-5p, 891a-5p, 200a-5p, and 6832-3p. From these miRNAs, 609 target genes were predicted and classified into 75 pathways, including angiogenesis, G-protein coupled receptors (GPCRs), inflammation mediated by chemo/cytokines, and integrin signaling. Target genes within these notable pathways included EPHA3, PDGFA, PTK2/FAK1, and IL15. Conclusions We identified 9 significantly downregulated miRNAs in the blood of colorectal cancer patients who developed VTE compared to controls in this pilot study. These data suggest that colorectal cancer patients may express unique miRNA profiles prior to VTE development which may be useful as biomarkers in future predictive models. In addition, this study identified potential new mechanistic targets for understanding cancer-associated thrombosis. While the role of GPCRs, integrins, and inflammation in platelet activation and function is widely known, this study also identified factors within the angiogenesis pathway that have been linked to increased platelet aggregation and tissue factor activation. Thus, downregulation of inhibitory miRNAs may cause disinhibition of pathways important for platelet and vascular function and other prothrombotic factors. Disclosures Khorana: Janssen: Consultancy; Bayer: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy. McCrae:Pfizer Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Dova Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Rigel Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Sanofi Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Chronic Diseases among Older Cancer Survivors

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Laura Deckx ◽  
Marjan van den Akker ◽  
Job Metsemakers ◽  
André Knottnerus ◽  
François Schellevis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Venous Thrombosis ◽  
Cancer Patients ◽  
Chronic Diseases ◽  
Cancer Diagnosis ◽  
Cox Regression ◽  
Cox Regression Analysis ◽  
Older Cancer Patients ◽  
After Cancer ◽  
Colorectal Cancer Patients

Objective. To compare the occurrence of pre-existing and subsequent comorbidity among older cancer patients (≥60years) with older non-cancer patients.Material and Methods. Each cancer patient (n=3835, mean age 72) was matched with four non-cancer patients in terms of age, sex, and practice. The occurrence of chronic diseases was assessed cross-sectionally (lifetime prevalence at time of diagnosis) and longitudinally (incidence after diagnosis) for all cancer patients and for breast, prostate, and colorectal cancer patients separately. Cancer and non-cancer patients were compared using logistic and Cox regression analysis.Results. The occurrence of the most common pre-existing and incident chronic diseases was largely similar in cancer and non-cancer patients, except for pre-existing COPD (OR 1.21, 95% CI 1.06–1.37) and subsequent venous thrombosis in the first two years after cancer diagnosis (HR 4.20, 95% CI 2.74–6.44), which were significantly more frequent (P<0.01) among older cancer compared to non-cancer patients.Conclusion. The frequency of multimorbidity in older cancer patients is high. However, apart from COPD and venous thrombosis, the incidence of chronic diseases in older cancer patients is similar compared to non-cancer patients of the same age, sex, and practice.

scholarly journals The pattern of Comorbidities and Associated Risk Factors among Colorectal Cancer Patients in Spain: CoMCoR study

2019 ◽  
Author(s):  
Miguel Angel Luque-Fernandez ◽  
Daniel Redondo-Sánchez ◽  
Miguel Rodríguez-Barranco ◽  
Ma Carmen Carmona-García ◽  
Rafael Marcos-Gragera ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Surgical Treatment ◽  
Cancer Patients ◽  
Cancer Diagnosis ◽  
Web Application ◽  
Stage Iv ◽  
Chronic Obstructive ◽  
Limited Information ◽  
Colorectal Cancer Patients

AbstractColorectal cancer is the second most frequently diagnosed cancer in Spain. Cancer treatment and outcomes can be influenced by tumor characteristics, patient general health status and comorbidities. Numerous studies have analyzed the influence of comorbidity on cancer outcomes, but limited information is available regarding the frequency and distribution of comorbidities in colorectal cancer patients, particularly elderly ones, in the Spanish population. We developed a population-based high-resolution cohort study of all incident colorectal cancer cases diagnosed in Spain in 2011 to describe the frequency and distribution of comorbidities, as well as tumor and healthcare factors. We then characterized risk factors associated with the most prevalent comorbidities, as well as dementia and multimorbidity, and developed an interactive web application to visualize our findings. The most common comorbidities were diabetes (23.6%), chronic obstructive pulmonary disease (17.2%), and congestive heart failure (14.5%). Dementia was the most common comorbidity among patients aged ≥75 years. Patients with dementia had a 30% higher prevalence of being diagnosed at stage IV and the highest prevalence of emergency hospital admission after colorectal cancer diagnosis (33%). Colorectal cancer patients with dementia were nearly three times more likely to not be offered surgical treatment. Age ≥75 years, obesity, male sex, being a current smoker, having surgery more than 60 days after cancer diagnosis, and not being offered surgical treatment were associated with a higher risk of multimorbidity. Patients with multimorbidity aged ≥75 years showed a higher prevalence of hospital emergency admission followed by surgery the same day of the admission (37%). We found a consistent pattern in the distribution and frequency of comorbidities and multimorbidity among colorectal cancer patients. The high frequency of stage IV diagnosis among patients with dementia and the high proportion of older patients not being offered surgical treatment are significant findings that require policy actions.

Clinicopathological description of a subset of schistosoma mansoni associated colorectal cancer patients in an endemic area in Brazil.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15154-e15154
Author(s):  
Gustavo Fernandes Godoy Almeida ◽  
Mauricio Assuero Lima de Freitas ◽  
Mariana M M Lira ◽  
Ana Lucia Coutinho Domingues ◽  
Lais Neares ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Schistosoma Mansoni ◽  
Cancer Patients ◽  
Cancer Diagnosis ◽  
Endemic Area ◽  
Colorectal Carcinogenesis ◽  
Disease Rate ◽  
Genetic Profile ◽  
Node Metastasis ◽  
Colorectal Cancer Patients

e15154 Background: Schistosoma have been implicated in colorectal carcinogenesis. We aim to describe clinicopathological description of a subset of Schistosoma mansoni-associated colorectal cancer patients in an endemic area in Brazil. Methods: We have performed a survey at cancer registry and identified those colorectal cancer patients who underwent biopsy and/or surgery in our institution in the last 10 years. We performed a comparison between Schistosoma- and non-Schistosoma colorectal cancer patients. T-test were performed to compare clinico-pathological features. Results: 300 hundred patients were identified. From this population, 83 patients had encounters at gastroenterology unit, where schistosoma patients (among those with other diseases) are treated. Among them, 7 patients presented both conditions (colorectal cancer and schistosomiasis), corresponding to 8.4% of these selected population. We identified diferences among Schistosoma- and non-Schistosoma colorectal patients neither in age of cancer diagnosis nor in terms of laterality. We did not find diferences in terms of metastatic disease rate between both populations, however, we have observed a higher incidence of limph node metastasis among Schistosoma colorectal patients. Conclusions: Schistosoma colorectal patients present similarity in terms of age of cancer diagnosis and laterality when compared to non-Schistosoma colorectal patients, however, lymph node metastasis are increased in this population. Next publications from our group will provide information about survival curves and genetic profile.

scholarly journals 633Poorly controlled diabetes is a predictor of colorectal cancer survival

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Ming Li ◽  
David Roder
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Cancer Diagnosis ◽  
Cancer Survival ◽  
Epidemiological Studies ◽  
Colorectal Cancer Survival ◽  
Increased Risk ◽  
History Of ◽  
Colorectal Cancer Patients ◽  
The Impact

Abstract Background Epidemiological studies have shown diabetes associated with increased risk of colorectal cancer. This study investigates the impact of a pre-cancer diabetes-related hospitalization record on colorectal cancer survival. Methods A retrospective cohort of 13190 colorectal cancer patients recorded on the South Australian Cancer Registry in 2003-2013 were examined. Diabetes-related hospitalization histories were obtained using linked inpatient data. Colorectal cancer deaths were available for 2003-2013. The association of survival from colorectal cancer with diabetes-related hospitalization history was assessed using competing risk analysis, adjusting for sociodemographic factors and cancer stage at diagnosis. Results 2765 patients with colorectal cancer (26.5%) had a history of hospital admission for diabetic complications, the most common being multiple complications (32%), followed by kidney and eye complications. The 5- and 10-year cancer survival probabilities were 63% and 56% in those with a diabetes complication history, significantly lower than 66% and 60% for patients without these complications (adjusted sub hazard ratio 1.11, 95% CI 1.02-1.20). Risk of colorectal cancer death was lower when theses diabetes-related hospitalizations were earlier than the year of cancer diagnosis - i.e., adjusted SHR 0.80, 95% CI 0.66-0.97 for 3-5 and 0.76, 95% CI 0.59-0.98 for 6+ years before the cancer diagnosis compared with same-year hospitalizations. Conclusions Colorectal cancer patients with a history of diabetes-related hospitalization have poorer survival, particularly if these hospitalizations were in the same year as the cancer diagnosis. Key messages Poorly controlled diabetes histories predict increased risk of colorectal cancer mortality.

scholarly journals Is There an Increased Risk of ALL in Patients with First Cancers Treated with Radiotherapy and/or Chemotherapy?

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 900-900
Author(s):  
Remco J Molenaar ◽  
Tomas Radivoyevitch ◽  
Aaron T. Gerds ◽  
Aziz Nazha ◽  
Hetty E. Carraway ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Board Of Directors ◽  
Cancer Patients ◽  
Cancer Diagnosis ◽  
Lymphoblastic Leukemia ◽  
Age At Diagnosis ◽  
Regression Analyses ◽  
Advisory Committees ◽  
Increased Risk ◽  
The Us

Abstract Background External-beam radiotherapy (RT) and chemotherapy (CT) are commonly used modalities in cancer therapy and have been associated with increased risk of second hematological malignancies, especially myeloid neoplasms. Acute lymphoblastic leukemia (ALL) is typically not considered a treatment-related complication and the risk of ALL in patients treated with chemotherapy and radiation for other cancers is poorly defined. In this study, we interrogated the US Surveillance Epidemiology and End Results (SEER) registry to analyze the risks of ALL in cancer patients treated with RT, CT or combined modality regimens at the population level. Methods We used our previously validated R program, SEERaBomb (Leukemia 2016; 30: 285-94) to query all 18 SEER registries, 1973-2014. We identified all first cancer cases treated with RT and/or CT that subsequently developed ALL ≥1 year after diagnosis of the first cancer. First cancer cases of lymphoid lineage were excluded. Diagnosis was derived from the International Classification of Diseases. Relative risk (RR) time courses for developing ALL after treatment of first cancers was calculated based on the ratio of the observed and expected cases of ALL. The expected number of ALL patients was calculated using the background incidence rates of ALL in the US population and the person-years at risk for ALL after treatment of first cancer. RRs were adjusted for age at diagnosis, sex, and year of diagnosis. Multivariate Cox regression analyses were used to calculate hazards of ALL development to adjust for more covariates. Results In total, 4,851,222 eligible first cancer patients were identified, of whom 821,004 (17%) received RT only, 571,035 (12%) received CT only, 488,930 (10%) received RT + CT and 2,970,253 (61%) received neither. A total of 849 patients developed ALL; 176 (21%) in the RT only group, 137 (16%) in the CT only group, 106 (12%) in the RT + CT group and 430 (51%) in the no RT/CT group. Compared to the risk in general population, patients treated with CT or RT had an elevated risk of developing ALL in the first 10 years after first cancer diagnosis (RR for RT only, 1.59 [95% CI 1.33-1.88] P < 0.0001; RR for CT only, 3.47 [2.87-4.16] P < 0.0001; RR for CT + RT, 3.22 [2.69-3.97] P < 0.0001). Patients with prior cancers but not treated with these modalities had no increased risks for ALL (RR for no RT/CT, 1.05 [0.93-1.17] P = 0.44; see Figure). In a more homogeneous cohort of breast cancer patients, elevated risks of developing ALL in the first 10 years after breast cancer diagnosis were seen in patients treated with CT + RT (RR, 3.46 [2.46-4.73] P < 0.0001) or RT only (RR, 1.82 [1.33-2.43] P = 0.0001) but not in those treated with CT only (RR, 1.76 [0.98-2.89] P = 0.06) or no CT/RT (RR, 0.77 [0.53-1.07] P = 0.15). In multivariate regression analyses in the entire cohort of cancer patients, significant predictors for subsequent ALL were younger age at diagnosis, male sex, receipt of CT or RT and if a non-lymphoid hematological malignancy preceded development of ALL (Table 1). Among patients with solid tumors as first cancers, CT + RT was associated with the highest hazards for developing ALL followed by RT only and then CT. Among patients with hematological first cancers, CT only, but not CT + RT or RT only, was associated with increased hazards for ALL. Conclusion Among patients treated for a first cancer, receipt of RT and/or CT was associated with higher relative risks and hazards for developing ALL than those not receiving cytotoxic modalities. Patients with hematologic first cancers (myeloid lineage or plasma cell dyscrasias) had the highest hazards of developing ALL as second cancer. When considering the risk kinetics and subgroup analyses in patients with solid first cancers, RT only or RT + CT, but not CT only, associate with increased risks for ALL. To our knowledge this is the largest evaluation of the risk of ALL in cancer patients treated with various modalities. Differentially elevated risks of ALL observed in cancer cohorts based on the treatment modality that was received for a prior cancer suggests a possible biological mechanism that needs to be explored further. Disclosures Gerds: Celgene: Consultancy; CTI Biopharma: Consultancy; Apexx Oncology: Consultancy; Incyte: Consultancy. Nazha:MEI: Consultancy. Carraway:Jazz: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Speakers Bureau; Balaxa: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; FibroGen: Consultancy; Novartis: Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Majhail:Incyte: Honoraria; Anthem, Inc.: Consultancy; Atara: Honoraria. Maciejewski:Apellis Pharmaceuticals: Consultancy; Ra Pharmaceuticals, Inc: Consultancy; Ra Pharmaceuticals, Inc: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Apellis Pharmaceuticals: Consultancy. Sekeres:Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Prevalence of Depression and Anxiety in Colorectal Cancer Patients: A Literature Review

2019 ◽  
Vol 16 (3) ◽  
pp. 411 ◽  
Author(s):  
Yu-Ning Peng ◽  
Mei-Li Huang ◽  
Chia-Hung Kao
Keyword(s):  
Colorectal Cancer ◽  
Literature Review ◽  
Cancer Patients ◽  
Web Of Science ◽  
Depression And Anxiety ◽  
Lower Prevalence ◽  
High Prevalence ◽  
Prevalence Of Depression ◽  
After Cancer ◽  
Colorectal Cancer Patients

Background: We aimed to review published studies to obtain the best estimate of the risk of depression and anxiety among colorectal cancer (CRC) patients. Methods: We searched the PubMed/Medline database, Web of Science, and Google Scholar on the prevalence of depression or anxiety in CRC patients. A review of 15 studies published between June 1967 and June 2018 were conducted, and 93,805 CRC patients were included. Results: The prevalence of depression among patients diagnosed with CRC ranged from 1.6%–57%, and those of anxiety ranged from 1.0%–47.2%. Studies in which an expert (psychiatrist) administered the interviews reported lower prevalence of both depression and anxiety. Conclusion: The findings of this review suggest that patients with CRC exhibited a significantly high prevalence of both depression and anxiety, and these symptoms can persist even after cancer treatment is completed. However, the correlation of age and the emergence of depression or anxiety in CRC patients still remain controversial.

scholarly journals The diagnostic value of serum microRNA-183 and TK1 as biomarkers for colorectal cancer diagnosis

2017 ◽  
Vol 12 (1) ◽  
pp. 243-247
Author(s):  
Xiangrong Zhu ◽  
Xiongtie Wang ◽  
Xihua Chen
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Cancer Diagnosis ◽  
Serum Levels ◽  
Diagnostic Value ◽  
Healthy Controls ◽  
Significant Statistical Difference ◽  
Median Serum ◽  
Colorectal Cancer Patients ◽  
Sensitivity Specificity

AbstractObjectiveTo evaluate the serum levels of microRNA-183 (miR-183) and thymidine kinase 1 (TK1) in colorectal cancer patients and their clinical value as biomarkers for colorectal cancer auxiliary diagnosis.MethodsForty-six pathology confirmed colorectal cancer patients and 46 healthy controls were included in this study. The serum levels of miR-183 and TK1 in colorectal cancer patients and healthy controls were examined by real-time PCR and chemiluminescence detection assay respectively. The diagnostic value of serum miR-183 and TK1 as tumor biomarkers for colorectal cancer detection was evaluated through receiver operating characteristic (ROC) curves.ResultsThe median serum relative expression of miR-183 was 1.33 (0.34-5.65) and 0.88 (0.26-4.67) in colorectal cancer patients and healthy controls respectively with significant statistical difference (p<0.05). Using serum miR-183 as the diagnostic reference, the colorectal cancer diagnosis sensitivity, specificity and AUC was 65.22%, 63.04% and 0.69 respectively. The median serum level of TK1 was 3.33 (0.78-5.78) pmol/L and 0.99 (0.34-4.46) pmol/L in colorectal cancer patients and healthy controls respectively with significant statistical difference (p<0.05). The diagnostic sensitivity, specificity and AUC was 84.78%, 78.26% and 0.88 respectively forserum TK1 as reference for colorectal diagnosis. The pearson correlation test was used to evaluate the serum miR-183 and TK1 correlation in colorectal cancer patients. However, no significant correlation between serum miR-183 and TK1 was found in colorectal patients (p>0.05).ConclusionSerum levels of miR-183 and TK1 arepotential biomarkers for colorectal cancer auxiliary diagnosis.

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