Identification of a biomarker panel for colorectal cancer diagnosis

Background Malignancies arising in the large bowel cause the second largest number of deaths from cancer in the Western World. Despite progresses made during the last decades, colorectal cancer remains one of the most frequent and deadly neoplasias in the western countries. Methods A genomic study of human colorectal cancer has been carried out on a total of 31 tumoral samples, corresponding to different stages of the disease, and 33 non-tumoral samples. The study was carried out by hybridisation of the tumour samples against a reference pool of non-tumoral samples using Agilent Human 1A 60-mer oligo microarrays. The results obtained were validated by qRT-PCR. In the subsequent bioinformatics analysis, gene networks by means of Bayesian classifiers, variable selection and bootstrap resampling were built. The consensus among all the induced models produced a hierarchy of dependences and, thus, of variables. Results After an exhaustive process of pre-processing to ensure data quality--lost values imputation, probes quality, data smoothing and intraclass variability filtering--the final dataset comprised a total of 8, 104 probes. Next, a supervised classification approach and data analysis was carried out to obtain the most relevant genes. Two of them are directly involved in cancer progression and in particular in colorectal cancer. Finally, a supervised classifier was induced to classify new unseen samples. Conclusions We have developed a tentative model for the diagnosis of colorectal cancer based on a biomarker panel. Our results indicate that the gene profile described herein can discriminate between non-cancerous and cancerous samples with 94.45% accuracy using different supervised classifiers (AUC values in the range of 0.997 and 0.955)

Identification of a biomarker panel for colorectal cancer diagnosis

Background:Malignancies arising in the large bowel cause the second largest number of deaths from cancer in the Western World. Despite progresses made during the last decades, colorectal cancer remains one of the most frequent and deadly neoplasias in the western countries. Methods: A genomic study of human colorectal cancer has been carried out on a total of 31 tumoral samples, corresponding to different stages of the disease, and 33 non-tumoral samples. The study was carried out by hybridisation of the tumour samples against a reference pool of non-tumoral samples using Agilent Human 1A 60-mer oligo microarrays. The results obtained were validated by qRT-PCR. In the subsequent bioinformatics analysis, gene networks by means of Bayesian classifiers, variable selection and bootstrap resampling were built. The consensus among all the induced models produced a hierarchy of dependences and, thus, of variables. Results: After an exhaustive process of pre-processing to ensure data quality--lost values imputation, probes quality, data smoothing and intraclass variability filtering--the final dataset comprised a total of 8, 104 probes. Next, a supervised classification approach and data analysis was carried out to obtain the most relevant genes. Two of them are directly involved in cancer progression and in particular in colorectal cancer. Finally, a supervised classifier was induced to classify new unseen samples. Conclusions: We have developed a tentative model for the diagnosis of colorectal cancer based on a biomarker panel. Our results indicate that the gene profile described herein can discriminate between non-cancerous and cancerous samples with 94.45% accuracy using different supervised classifiers (AUC values in the range of 0.997 and 0.955).

Current cancer research on breast cancer : diagnosis, prognosis, and treatment.

Prepared for the ICRDB Program by the Current Cancer Research Project Analysis Center.

An investigation of routes to cancer diagnosis in 10 international jurisdictions, as part of the International Cancer Benchmarking Partnership: survey development and implementation

Objectives This paper describes the methods used in the International Cancer Benchmarking Partnership Module 4 Survey (ICBPM4) which examines time intervals and routes to cancer diagnosis in 10 jurisdictions. We present the study design with defining and measuring time intervals, identifying patients with cancer, questionnaire development, data management and analyses.
Design and setting Recruitment of participants to the ICBPM4 survey is based on cancer registries in each jurisdiction. Questionnaires draw on previous instruments and have been through a process of cognitive testing and piloting in three jurisdictions followed by standardised translation and adaptation. Data analysis focuses on comparing differences in time intervals and routes to diagnosis in the jurisdictions.
Participants Our target is 200 patients with symptomatic breast, lung, colorectal and ovarian cancer in each jurisdiction. Patients are approached directly or via their primary care physician (PCP). Patients’ PCPs and cancer treatment specialists (CTSs) are surveyed, and ‘data rules’ are applied to combine and reconcile conflicting information. Where CTS information is unavailable, audit information is sought from treatment records and databases.
Main outcomes Reliability testing of the patient questionnaire showed that agreement was complete (κ=1) in four items and substantial (κ=0.8, 95% CI 0.333 to 1) in one item. The identification of eligible patients is sufficient to meet the targets for breast, lung and colorectal cancer. Initial patient and PCP survey response rates from the UK and Sweden are comparable with similar published surveys. Data collection was completed in early 2016 for all cancer types.
Conclusion An international questionnaire-based survey of patients with cancer, PCPs and CTSs has been developed and launched in 10 jurisdictions. ICBPM4 will help to further understand international differences in cancer survival by comparing time intervals and routes to cancer diagnosis.

Cancer diagnosis disclosure from Portuguese physicians

OBJECTIVE: Doctor-patient communication in oncology, particularly concerning diagnostic disclosure, is a crucial factor related to the quality of the doctor-patient relationship and the psychological state of the patient. The aims of our study were to investigate physicians' opinions and practice with respect to disclosure of a cancer diagnosis and to explore potential related factors. METHOD: A self-report questionnaire developed for our study was responded to by 120 physicians from Coimbra University Hospital Centre and its primary healthcare units. RESULTS: Some 91.7% of physician respondents generally disclosed a diagnosis, and 94.2% were of the opinion that the patient knowing the truth about a diagnosis had a positive effect on the doctor-patient relationship. A need for training about communicating with oncology patients was reported by 85.8% of participants. The main factors determining what information to provide to patients were: (1) patient intellectual and cultural level, (2) patient desire to know the truth, and (3) the existence of family. SIGNIFICANCE OF RESULTS: Our results point to a paradigm shift in communication with cancer patients where disclosure of the diagnosis should be made part of general clinical practice. Nevertheless, physicians still experience difficulties in revealing cancer diagnoses to patients and often lack the skills to deal with a patient's emotional responses, which suggests that more attention needs to be focused on communication skills training programs.

Cancer diagnosis disclosure from Portuguese physicians

OBJECTIVE: Doctor-patient communication in oncology, particularly concerning diagnostic disclosure, is a crucial factor related to the quality of the doctor-patient relationship and the psychological state of the patient. The aims of our study were to investigate physicians' opinions and practice with respect to disclosure of a cancer diagnosis and to explore potential related factors. METHOD: A self-report questionnaire developed for our study was responded to by 120 physicians from Coimbra University Hospital Centre and its primary healthcare units. RESULTS: Some 91.7% of physician respondents generally disclosed a diagnosis, and 94.2% were of the opinion that the patient knowing the truth about a diagnosis had a positive effect on the doctor-patient relationship. A need for training about communicating with oncology patients was reported by 85.8% of participants. The main factors determining what information to provide to patients were: (1) patient intellectual and cultural level, (2) patient desire to know the truth, and (3) the existence of family. SIGNIFICANCE OF RESULTS: Our results point to a paradigm shift in communication with cancer patients where disclosure of the diagnosis should be made part of general clinical practice. Nevertheless, physicians still experience difficulties in revealing cancer diagnoses to patients and often lack the skills to deal with a patient's emotional responses, which suggests that more attention needs to be focused on communication skills training programs.

Healthcare providers’ knowledge, attitude and behaviour towards breast cancer diagnosis and treatment in Malaysia – a mini systematic review

Breast cancer is the most common cancer among women in Malaysia. Therefore, it is important for the public to be educated on breast cancer and to know the steps that need to be taken to detect it early. Healthcare providers are in a unique position to provide public health education due to their good knowledge of health issues and their roles in healthcare. A systematic review of studies conducted from 2008 till 2015 was undertaken to analyze the knowledge, attitudes and behavior of Malaysian healthcare providers regarding breast cancer, in an attempt to obtain an overall picture of how wellequipped the healthcare providers are to provide optimal breast cancer education, and to ascertain their perceptions and actual involvement in such education. The systematic review was conducted via a primary search of various databases and journal websites, and a secondary search of references cited in eligible studies. Criteria for eligibility include studies conducted in Malaysia and published from the year 2008 to 2015, and written in English language. A total of fifteen articles were identified and reviewed but only two studies were eligible for this review. The findings suggest that future and current Malaysian healthcare providers have moderate knowledge of breast cancer, showed a positive disposition towards involvement in breast cancer education, but displayed poor involvement.

Diagnosis of colorectal cancer using Raman spectroscopy of laser-trapped single living epithelial cells

A single-cell diagnostic technique for epithelial cancers is developed by utilizing laser trapping and Raman spectroscopy to differentiate cancerous and normal epithelial cells. Single-cell suspensions were prepared from surgically removed human colorectal tissues following standard primary culture protocols and examined in a near-infrared laser-trapping Raman spectroscopy system, where living epithelial cells were investigated one by one. A diagnostic model was built on the spectral data obtained from 8 patients and validated by the data from 2 new patients. Our technique has potential applications from epithelial cancer diagnosis to the study of cell dynamics of carcinogenesis. (c) 2006 Optical Society of America.

Digoxin use after diagnosis of breast cancer and survival: a population-based cohort study

Digoxin has been shown to have an estrogenic effect and is associated with increased risk of gynecomastia and estrogen-sensitive cancers such as breast and uterus cancer. These findings, particularly recent observations of increased breast cancer risk, raise questions about the safety of digoxin use in breast cancer patients. Therefore, we investigated whether digoxin use after breast cancer diagnosis increased the risk of breast cancer-specific mortality in breast cancer patients. A cohort of 17,842 breast cancer patients newly diagnosed from 1998 to 2009 was identified from English cancer registries (from the National Cancer Data Repository). This cohort was linked to the UK Clinical Practice Research Datalink (to provide digoxin and other prescription records) and to the Office of National Statistics mortality data (to identify breast cancer-specific deaths). Using time-dependent Cox regression models, unadjusted and adjusted hazard ratios (HR) and 95 % confidence intervals (CIs) were calculated for the association between post-diagnostic exposure to digoxin and breast cancer-specific and all-cause mortality. In 17,842 breast cancer patients, there were 2219 breast cancer-specific deaths. Digoxin users appeared to have increased breast cancer-specific mortality compared with non-users (HR 1.73; 95 % CI 1.39–2.15) but this association was entirely attenuated after adjustment for potential confounders (adjusted HR 0.91; 95 % CI 0.72–1.14). In this large population-based breast cancer cohort study, there was little evidence of an increase in breast cancer-specific mortality with digoxin use after diagnosis. These results provide some reassurance that digoxin use is safe in breast cancer patients.

Statin use after diagnosis of breast cancer and survival: a population-based cohort study

BACKGROUND: Preclinical studies have shown that statins, particularly simvastatin, can prevent growth in breast cancer cell lines and animal models. We investigated whether statins used after breast cancer diagnosis reduced the risk of breast cancer-specific, or all-cause, mortality in a large cohort of breast cancer patients.

METHODS: A cohort of 17,880 breast cancer patients, newly diagnosed between 1998 and 2009, was identified from English cancer registries (from the National Cancer Data Repository). This cohort was linked to the UK Clinical Practice Research Datalink, providing prescription records, and to the Office of National Statistics mortality data (up to 2013), identifying 3694 deaths, including 1469 deaths attributable to breast cancer. Unadjusted and adjusted hazard ratios (HRs) for breast cancer-specific, and all-cause, mortality in statin users after breast cancer diagnosis were calculated using time-dependent Cox regression models. Sensitivity analyses were conducted using multiple imputation methods, propensity score methods and a case-control approach.

RESULTS: There was some evidence that statin use after a diagnosis of breast cancer had reduced mortality due to breast cancer and all causes (fully adjusted HR = 0.84 [95% confidence interval = 0.68-1.04] and 0.84 [0.72-0.97], respectively). These associations were more marked for simvastatin 0.79 (0.63-1.00) and 0.81 (0.70-0.95), respectively.

CONCLUSIONS: In this large population-based breast cancer cohort, there was some evidence of reduced mortality in statin users after breast cancer diagnosis. However, these associations were weak in magnitude and were attenuated in some sensitivity analyses.

Digoxin use after diagnosis of colorectal cancer and survival: a population-based cohort study.

BACKGROUND:

Digoxin has been shown to affect a number of pathways that are of relevance to cancer, and its use has been associated with increased risks of breast and uterus cancer and, more recently, a 40% increase in colorectal cancer risk. These findings raise questions about the safety of digoxin use in colorectal cancer patients, and, therefore, we investigated whether digoxin use after colorectal cancer diagnosis increased the risk of colorectal cancer-specific mortality.

METHODS:

A cohort of 10,357 colorectal cancer patients newly diagnosed from 1998 to 2009 was identified from English cancer registries and linked to the UK Clinical Practice Research Datalink (to provide digoxin and other prescription records) and to the Office of National Statistics mortality data (to identify 2,724 colorectal cancer-specific deaths). Using time-dependent Cox regression models, unadjusted and adjusted HRs and 95% confidence intervals (CI) were calculated for the association between postdiagnostic exposure to digoxin and colorectal cancer-specific mortality.

RESULTS:

Overall, 682 (6%) colorectal cancer patients used digoxin after diagnosis. Digoxin use was associated with a small increase in colorectal cancer-specific mortality before adjustment (HR, 1.25; 95% CI, 1.07-1.46), but after adjustment for confounders, the association was attenuated (adjusted HR, 1.10; 95% CI, 0.91-1.34) and there was no evidence of a dose response.

CONCLUSIONS:

In this large population-based colorectal cancer cohort, there was little evidence of an increase in colorectal cancer-specific mortality with digoxin use after diagnosis.

IMPACT:

These results provide some reassurance that digoxin use is safe in colorectal cancer patients.

Early detection of ovarian cancer in samples pre-diagnosis using CA125 and MALDI-MS peaks

Aim: A nested case-control discovery study was undertaken 10 test whether information within the serum peptidome can improve on the utility of CA125 for early ovarian cancer detection. Materials and Methods: High-throughput matrix-assisted laser desorption ionisation mass spectrometry (MALDI-MS) was used to profile 295 serum samples from women pre-dating their ovarian cancer diagnosis and from 585 matched control samples. Classification rules incorporating CA125 and MS peak intensities were tested for discriminating ability. Results: Two peaks were found which in combination with CA125 discriminated cases from controls up to 15 and 11 months before diagnosis, respectively, and earlier than using CA125 alone. One peak was identified as connective tissue-activating peptide III (CTAPIII), whilst the other was putatively identified as platelet factor 4 (PF4). ELISA data supported the down-regulation of PF4 in early cancer cases. Conclusion: Serum peptide information with CA125 improves lead time for early detection of ovarian cancer. The candidate markers are platelet-derived chemokines, suggesting a link between platelet function and tumour development.

Cancer risk factors, diagnosis and sexual identity in the Australian longitudinal study of women's health

PURPOSE: We sought to examine cancer diagnosis, cancer treatment, and related risk factors among Australian, middle-aged, exclusively heterosexual women compared with sexual minority women (SMW; mainly heterosexual, bisexual, mainly lesbian, and lesbian). METHODS: Secondary data analysis of the Australian Longitudinal Study of Women's Health for women born in 1946 through 1951 (n = 10,451) included bivariate tests (i.e., contingency table analyses, independent t tests). RESULTS: SMW did not have significantly higher cancer diagnoses compared with exclusively heterosexual women, although they were more likely to report never having had a mammogram or pap smear. SMW were also significantly more likely to be high-risk drinkers (11.1% vs. 6.8%; p < .05), current smokers (15.1% vs. 8.3%; p < .001), report significantly higher rates of depression (mean ± SD; 6.4 ± 5.5 vs. 5.4 ± 5.1; p < .01.), have experienced physical abuse (10.2% vs. 5.1%; p < .001), and been in a violent relationship (27.2% vs. 12.8%; p < .001). CONCLUSION: SMW had higher rates of several known cancer risk factors, ostensibly placing them at higher risk of cancer as well as chronic health conditions. Further research is needed to determine whether increased risk results in increased cancer as these women age, and to inform the development of interventions to reduce the risk of disease for SMW.