MicroRNAs (miRNAs) regulate gene expression by binding to mRNA, and can function as oncogenes or tumor suppressors depending on the target. In this study, using qRT-PCR, we examined the expression of ...six miRNAs (miR-21, miR-31, miR-92a, miR-101, miR-106a and miR-145) in tumors from 193 prospectively recruited patients with colorectal cancer, and associations with clinicopathological parameters and patient outcome were analyzed. The miRNAs were chosen based on previous studies for their biomarker potential and suggested biological relevance in colorectal cancer.
The miRNA expression was examined by qRT-PCR. Associations between miRNA expression and clinicopathological variables were explored using Mann-Whitney U and Kruskal-Wallis test while survival was estimated using the Kaplan-Meier method and compared using the log-rank test.
MiR-101 was hardly expressed in the tumor samples, while for the other miRNAs, variable expression levels and expression ranges were observed, with miR-21 being most abundantly expressed relative to the reference (RNU44). In our study cohort, major clinical significance was demonstrated only for miR-31, as high expression was associated with advanced tumor stage and poor differentiation. No significant associations were found between expression of the investigated miRNAs and metastasis-free or overall survival.
Investigating the expression of six miRNAs previously identified as candidate biomarkers in colorectal cancer, few clinically relevant associations were detected in our patient cohort. Our results emphasize the importance of validating potential tumor markers in independent patient cohorts, and indicate that the role of miRNAs as colorectal cancer biomarkers is still undetermined.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Increasing attendance to screening offers the best potential for improving the effectiveness of well-established cervical cancer screening programs. Self-sampling at home for human papillomavirus ...(HPV) testing as an alternative to a clinical sampling can be a useful policy to increase attendance. To determine whether self-sampling improves screening attendance for women who do not regularly attend the Norwegian Cervical Cancer Screening Programme (NCCSP), 800 women aged 25-69 years in the Oslo area who were due to receive a 2nd reminder to attend regular screening were randomly selected and invited to be part of the intervention group. Women in this group received one of two self-sampling devices, Evalyn Brush or Delphi Screener. To attend screening, women in the intervention group had the option of using the self-sampling device (self-sampling subgroup) or visiting their physician for a cervical smear. Self-sampled specimens were split and analyzed for the presence of high-risk (hr) HPV by the CLART® HPV2 test and the digene® Hybrid Capture (HC)2 test. The control group consisted of 2593 women who received a 2nd reminder letter according to the current guidelines of the NCCSP. The attendance rates were 33.4% in the intervention group and 23.2% in the control group, with similar attendance rates for both self-sampling devices. Women in the self-sampling subgroup responded favorably to both self-sampling devices and cited not remembering receiving a call for screening as the most dominant reason for previous non-attendance. Thirty-two of 34 (94.1%) hrHPV-positive women in the self-sampling subgroup attended follow-up. In conclusion, self-sampling increased attendance rates and was feasible and well received. This study lends further support to the proposal that self-sampling may be a valuable alternative for increasing cervical cancer screening coverage in Norway.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Colorectal cancer (CRC) is one of the leading causes of cancer related deaths and the search for prognostic biomarkers that might improve treatment decisions is warranted. MicroRNAs (miRNAs) are ...short non-coding RNA molecules involved in regulating gene expression and have been proposed as possible biomarkers in CRC. In order to characterize the miRNA transcriptome, a large cohort including 88 CRC tumors with long-term follow-up was deep sequenced. 523 mature miRNAs were expressed in our cohort, and they exhibited largely uniform expression patterns across tumor samples. Few associations were found between clinical parameters and miRNA expression, among them, low expression of miR-592 and high expression of miR-10b-5p and miR-615-3p were associated with tumors located in the right colon relative to the left colon and rectum. High expression of miR-615-3p was also associated with poorly differentiated tumors. No prognostic biomarker candidates for overall and metastasis-free survival were identified by applying the LASSO method in a Cox proportional hazards model or univariate Cox. Examination of the five most abundantly expressed miRNAs in the cohort (miR-10a-5p, miR-21-5p, miR-22-3p, miR-143-3p and miR-192-5p) revealed that their collective expression represented 54% of the detected miRNA sequences. Pathway analysis of the target genes regulated by the five most highly expressed miRNAs uncovered a significant number of genes involved in the CRC pathway, including APC, TGFβ and PI3K, thus suggesting that these miRNAs are relevant in CRC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Micro-Abstract The impact of long intergenic noncoding RNA (lincRNA)-p21 on colorectal cancer (CRC) progression was investigated in this study. Wild-type p53 induces endogenous lincRNA-p21 in HCT-116 ...colon cancer cells. Elevated levels of lincRNA-p21 were significantly associated with CRC disease state, pT, and vascular invasion, indicating that lincRNA-p21 may contribute to CRC progression.
•Self-collection is comparable to current practice for detecting cervical lesions.•Collection devices may have impact on disease detection and on acceptability.•Delays in specimen preparation can ...notably affect the performance of self-collection.•Only validated procedure should be used and any delays should be minimized.
Comparative data on different self-collection methods is limited.
To assess the impact of hrHPV testing of two self-collection devices for detection of cervical carcinoma and high-grade lesions.
Three hundred ten patients collected two cervicovaginal specimens using a brush (Evalyn®Brush) and a swab (FLOQSwabs™), and filled a questionnaire at home. Then, a physician at the clinic took a cervical specimen into PreservCyt® buffer for hrHPV testing and cytology. All specimens were tested using Anyplex™ II HPV28, Cobas® 4800 HPV Test and Xpert®HPV.
Performance comparison included 45 cervical carcinomas and 187 patients with premalignant lesions. Compared to the physician-specimen, hrHPV testing of Evalyn®Brush showed non-inferior sensitivity for CIN3+ (relative sensitivity of Anyplex™ 0.99; Cobas® 0.96; Xpert®HPV 0.97) while hrHPV testing of FLOQSwabs™ showed inferior sensitivity (relative sensitivity of Anyplex™ 0.91; Cobas® 0.92; Xpert®HPV 0.93). Similar results were observed for invasive carcinomas albeit that FLOQSwabs™ was statistically non-inferior to the physician-specimen. Self-collection by either Evalyn®Brush or FLOQSwabs™ was more sensitive for CIN3+ than LSIL or worse cytology. Significant decrease in sensitivity for CIN3+ were observed for FLOQSwabs™ when specimens were preprocessed for hrHPV testing after 28 days. Both devices were well accepted, but patients considered Evalyn®Brush easier and more comfortable than FLOQSwabs™.
Self-collection is comparable to current screening practice for detecting cervical carcinoma and CIN3+ but device and specimen processing effects exist. Only validated procedure including collection device, hrHPV assay and specimen preparation should be used.
Following the demonstration that histone deacetylase inhibitors enhanced experimental radiation-induced clonogenic suppression, the Pelvic Radiation and Vorinostat (PRAVO) phase 1 study, combining ...fractionated radiotherapy with daily vorinostat for pelvic carcinoma, was designed to evaluate both clinical and novel biomarker endpoints, the latter relating to pharmacodynamic indicators of vorinostat action in clinical radiotherapy.
Potential biomarkers of vorinostat radiosensitizing action, not simultaneously manifesting molecular perturbations elicited by the radiation itself, were explored by gene expression array analysis of study patients' peripheral blood mononuclear cells (PBMC), sampled at baseline (T0) and on-treatment two and 24 hours (T2 and T24) after the patients had received vorinostat.
This strategy revealed 1,600 array probes that were common for the comparisons T2 versus T0 and T24 versus T2 across all of the patients, and furthermore, that no significantly differential expression was observed between the T0 and T24 groups. Functional annotation analysis of the array data showed that a significant number of identified genes were implicated in gene regulation, the cell cycle, and chromatin biology. Gene expression was validated both in patients' PBMC and in vorinostat-treated human carcinoma xenograft models, and transient repression of MYC was consistently observed.
Within the design of the PRAVO study, all of the identified genes showed rapid and transient induction or repression and therefore, in principle, fulfilled the requirement of being pharmacodynamic biomarkers of vorinostat action in fractionated radiotherapy, possibly underscoring the role of MYC in this therapeutic setting.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
MicroRNAs as Biomarkers in Colorectal Cancer Schee, Kristina; Fodstad, Øystein; Flatmark, Kjersti
The American journal of pathology,
10/2010, Letnik:
177, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Colorectal cancer is a leading cause of cancer-related morbidity and mortality in the Western world. While improved diagnostic surveillance and treatment strategies involving surgery, chemo-, and ...radiotherapy have all contributed to earlier detection and improved survival, treatment decisions are still made almost exclusively based on the cancer's clinicopathological stage at diagnosis. Therefore, the search for new biomarkers to facilitate early diagnosis and individualized treatment is particularly warranted. MicroRNAs (miRNAs) are short, noncoding RNAs that regulate gene expression through posttranscriptional interactions with mRNA, thereby potentially leading to a vast range of downstream effects that depend on the target proteins affected. The discovery that miRNAs may act as either oncogenes or tumor suppressors has initiated extensive research in the cancer field, leading to the identification of numerous miRNAs implicated in carcinogenesis and tumor progression. MiRNAs are chemically stable and can thus be detected in a broad range of clinical samples, making these molecules particularly attractive as potential biomarkers in cancer. While the knowledge of miRNA involvement in colorectal cancer biology is less extensive than for other cancer types and several targets with potential biological and clinical relevance have been identified, a significant amount of research is still needed. In this review, we explore the literature regarding the relevance of miRNAs in colorectal cancer, focusing in particular on miRNAs as potential diagnostic, prognostic, and predictive biomarkers.
Both major morphologic types of cervical cancer, squamous cell carcinoma (SCC) and adenocarcinoma (AC), are causally related to persistent infection with high‐risk human papillomavirus (hrHPV), but ...screening has primarily been effective at preventing SCC. We analysed incidence trends of cervical cancer in Norway stratified by morphologies over 55 years, and projected SCC incidence in the absence of screening by assessing the changes in the incidence rate of AC. The Cancer Registry of Norway was used to identify all 19,530 malignancies in the cervix diagnosed in the period 1956–2010. The majority of these (82.9%) were classified as SCCs, 10.5% as ACs and the remaining 6.6% were of other or undefined morphology. By joint‐point analyses of a period of more than five decades, the average annual percentage change in the age‐standardised incidence was −1.0 (95%CI: −2.1–0.1) for cervical SCC, 1.5 (95%CI:1.1–1.9) for cervical AC and −0.9 (95%CI: −1.4 to −0.3) for cervical cancers of other or undefined morphology. The projected age‐standardised incidence rate of cervical SCC in Norway, assuming no screening, was 28.6 per 100,000 woman‐years in 2010, which compared with the observed SCC rate of 7.3 corresponds to an estimated 74% reduction in SCC or a 68% reduction due to screening in the total cervical cancer burden. Cytology screening has impacted cervical cancer burden more than suggested by the overall observed cervical cancer incidence reduction since its peak in the mid‐1970s. The simultaneous substantial increase in cervical adenocarcinoma in Norway is presumably indicative of an increase in exposure to HPV over time.
What's new?
Estimates indicate that cervical cancer incidence has decreased by half since the expansion of cytology screening in the 1970s in Norway. The decline has been attributed to the prevention of squamous cell carcinoma. This study shows, however, that screening has impacted cervical cancer burden beyond the overall observed reduction in incidence. Analysis of more than 50 years of incidence trends by cancer morphology reveals that the actual proportion of cervical cancers prevented by screening in Norway was 68%, considerably larger than previous figures. The difference is attributed to an increase in the background risk of cervical adenocarcinoma.
Abstract
With over half a million new cases and 275,000 deaths each year, cervical cancer constitutes a major public health problem world-wide, ranking as the third most common cancer in women. ...Screening with Pap-smear has reduced cervical cancer related morbidity and mortality considerably. However, the challenge lies in making screening and treatment available to all women at risk.
Main objective of this study was to evaluate performance of high-risk human papillomavirus (hrHPV) testing on self-collected smears by women who did not attend to screening regularly. Specifically we were interested to observe if: i) use of different self-sampling devices for hrHPV was feasible in Norway and ii) will self-sampling enhance attendance among women with suboptimal screening? iii) which HPV test should be used to ensure optimal follow-up?
Following approval from the Regional Ethical Committee, we identified in Oslo, Norway, during April-May 2013, 3,393 women with sub-optimal screening history. To motivate screening attendance, two different interventions were randomly allocated: 1) 300 women in age 26-34 and 300 women in age of 35-49 years, and 200 women in age of 50-69 years, received either lavage based self-screener (Delphi ScreenerTM, Delphi Bioscience BV) or dry brush self-screener (Evalyn Brush®, Rovers, The Netherlands); 2) 2,593 received a routine reminder letter to make an appointment for a Pap-smear. Those, who returned self-sampling devices or who had screening smear taken in 6 months period were defined as attendees. The population-based screening registry was used to identify those who had a screening smear.
Returned self-sampling devices were tested for hrHPV by Hybrid Capture2 (HC2) High-Risk HPV DNA Test® (QIAGEN, Gaithersburg, MD, USA) and HPV genotyped (CLART, Genomica, Madrid, Spain).
Out of 800, 80 women declined to participate in the self-sampling study and 720 devices was mailed out; 168 (23.3%) self-sampling devices were returned, 88 dry brush and 80 lavage-based self-sampling devices; in addition 59 had a Pap-smear (8.2%). 388 (14.7%) out of 2,593 who received a letter had a Pap-smear.
Overall hrHPV positivity rate, defined as positive either by CLART or HC2, was over 20% being highest in 26-34 years old (>30% ) and lowest in 50-69 years old (<15%). Only 13% were positive for both methods illustrating challenges in choosing HPV detection method when using self-sampling (preliminary results, based on 5-months follow-up).
The preliminary results show 31.5% participation for self-sampling group compared to 14.7% participation for the routine, reminder letter group.
Preliminary results indicate that i) it is feasible to use self-sampling device in routine screening; ii) use of self-sampling improves overall attendance of the screening program; iii) comparison of two different hrHPV detection methods will be presented in the conference.
Citation Format: Kristina Schee, Lönnberg Stefan, Helle Pedersen, Jesper Bonde, Mari Nygård. Improving attendance to the cervical cancer screening program: Does self-sampling at home improve cervical cancer prevention. abstract. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4135. doi:10.1158/1538-7445.AM2014-4135
Both major morphologic types of cervical cancer, squamous cell carcinoma (SCC) and adenocarcinoma (AC), are causally related to persistent infection with high‐risk human papillomavirus (hrHPV), but ...screening has primarily been effective at preventing SCC. We analysed incidence trends of cervical cancer in Norway stratified by morphologies over 55 years, and projected SCC incidence in the absence of screening by assessing the changes in the incidence rate of AC. The Cancer Registry of Norway was used to identify all 19,530 malignancies in the cervix diagnosed in the period 1956–2010. The majority of these (82.9%) were classified as SCCs, 10.5% as ACs and the remaining 6.6% were of other or undefined morphology. By joint‐point analyses of a period of more than five decades, the average annual percentage change in the age‐standardised incidence was −1.0 (95%CI: −2.1–0.1) for cervical SCC, 1.5 (95%CI:1.1–1.9) for cervical AC and −0.9 (95%CI: −1.4 to −0.3) for cervical cancers of other or undefined morphology. The projected age‐standardised incidence rate of cervical SCC in Norway, assuming no screening, was 28.6 per 100,000 woman‐years in 2010, which compared with the observed SCC rate of 7.3 corresponds to an estimated 74% reduction in SCC or a 68% reduction due to screening in the total cervical cancer burden. Cytology screening has impacted cervical cancer burden more than suggested by the overall observed cervical cancer incidence reduction since its peak in the mid‐1970s. The simultaneous substantial increase in cervical adenocarcinoma in Norway is presumably indicative of an increase in exposure to HPV over time.
What's new?
Estimates indicate that cervical cancer incidence has decreased by half since the expansion of cytology screening in the 1970s in Norway. The decline has been attributed to the prevention of squamous cell carcinoma. This study shows, however, that screening has impacted cervical cancer burden beyond the overall observed reduction in incidence. Analysis of more than 50 years of incidence trends by cancer morphology reveals that the actual proportion of cervical cancers prevented by screening in Norway was 68%, considerably larger than previous figures. The difference is attributed to an increase in the background risk of cervical adenocarcinoma.
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