Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “External validity”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,603 records · Page 89Linked to original sources
PubMed2005

Irritable-hostile depression: further validation as a bipolar depressive mixed state.

BACKGROUND: "Hostile depression" has unofficially long been described as a depressive subtype, but since DSM-III, the affect has been made a defining characteristic of borderline personality disorder. The related affect of irritability in DSM-IV-TR subsumes various hostile nuances and is included in the stem question for mood disorders--especially for hypomanic episodes; in children, it is nonetheless a sign of depression. Then, there is the unofficial more general concept of depression with anger attacks, until recently ostensibly a "unipolar" (UP) disorder. A veritable tower of Babel indeed. In the present analyses, our aim was to extend previous research on irritable-hostile depression to more specific parameters of bipolarity and depressive mixed state (DMX). METHODS: Consecutive 348 bipolar-II (BP-II) and 254 unipolar (UP) major depressive disorder (MDD) outpatients (off psychoactive agents, including substances of abuse), were interviewed with the Structured Clinical Interview for DSM-IV, the Hypomania Interview Guide, and the Family History Screen. Borderline personality, a confounding variable, rare in the FB setting, was excluded. Irritability was defined according to DSM-IV-TR, which includes various features of hostility and anger. Depressive mixed state (DMX) was defined as a major depressive episode (MDE) plus three or more concurrent intradepressive hypomanic symptoms, whether it occurred in BP-II or MDD. RESULTS: MDE with irritability was present in 59.7% (208/348) of BP-II and in 37.4% (95/254) of MDD (p=0.0000). In BP-II, MDE with, versus MDE without, irritability had significantly younger index age, higher rates of axis I comorbidity, atypical depressive features, and DMX. Upon logistic regression, we found a significant independent association between BP-II MDE with irritability and DMX. In UP, MDE with, versus without, irritability had significantly younger age and age at onset, higher rates of atypical depression, DMX, and bipolar family history. Logistic regression revealed a significant independent association between MDE with irritability and DMX. Given that we had excluded patients with borderline personality, the high prevalence of irritable-hostile depressives in this outpatient population means that hostility cannot be considered the signature of that personality. Factor analysis revealed independent "psychomotor activation" and "irritability-mental activation" factors. Odds ratios of irritability for DMX were highest in the "UP" MDD group (=12.2); for predicting DMX, irritability had the best psychometric profile of sensitivity of 66.3% and a specificity of 86.1% for this group as well. LIMITATION: We did not use specific instruments to measure irritable, hostile, and angry affects. CONCLUSIONS: These analyses show that irritable-hostile depression is distinct from agitated depression. Whether arising from a BP-II or MDD baseline, irritable-hostile depression emerges as a valid entity with strong links to external bipolar validators, such as bipolar family history. Irritable-hostile phenomenology in depression appears to be a strong clinical marker for a DMX. Irritable-hostile depression as a variant of DMX deserves the benefit of what seems to work best in practice, i.e., anticonvulsant mood stabilizers and/or atypical antipsychotics. Formal treatment studies are very much needed.

Adult↗
PubMedDate not supplied

[Validation of the French version of the Body Shape Questionnaire].

UNLABELLED: In today's societies, pressures from the idea of thinness are omnipresent and lead to a corporal dissatisfaction with an excessive preoccupation of the body's image. It seems important to have, in France, a device that can evaluate the corporal dissatisfaction degree, for the reason that the troubles of the body's image is a common diagnostical category to the anorexia and bulimia (DSM IV, 1994). Cooper et al. (1987) have developed one-dimensional questionnaire of 34 items in order to measure the worries towards the weight and the shape of the body, called the "Body Shape Questionnaire" (BSQ). Its concurrent validity has been shown with the using of the corporal dissatisfaction under-scale of the Eating Disorders Inventory (EDI; Garner et Olmsted, 1984) and the using of the diagnostical questionnaire: Eating Attitude Test (EAT; Garner et Garfinkel, 1979). The BSQ gives us a way to explore the role of extreme worries towards the body's apparence in the development, the keeping and the treatment of eating disorders. From this point the BSQ is a tool widely used on an international level in researches on the eating disorders. It has been validited in Spain and in Germany whereas it has not been yet subject to a validation in France. For this reason, we proposed to use the BSQ on the french population. METHODOLOGY: The sample is made of 242 university girl students. The average age is 20.7 years old with an standard deviation of 2.26. The size and the weight helped us to calculate the Body Mass Index (BMI) which is in fact the weight divided by the size squared. The average BMI is 21.06 kg/m2 +/- 2.87. Regarding the evaluating devices, the BSQ is presented as a scale of 34 items marked by 6 different points: 1 never, 2 barely, 3 sometimes, 4 often, 5 very often, 6 always. After getting the authorization form the authors to respect during these kinds of procedures, we have started validation. The corporal dissatisfaction under-scale of Eating Disorder Inventory (EDI, Garner et al., 1991) is made of 9 items and has a scale of 6 points going from "never" to "always". In order to evaluate the accuracy of the Body Shape Questionnaire (BSQ) in France, we made a test/retest. The concurrent validity of the BSQ has been evaluated by the EDI. The 242 subjects have been asked to fill in both questionnaires during the test and the re-test (4 weeks after the test). We have evaluated the accuracy of the BSQ with the calculation of the constancy test/retest (Pearson's r) and the measure of the internal consistency (Cronbach's alpha). Then, we tested the validity regarding an external criteria. The validation procedure is based here on an examination of the correlations between the tests results (BSQ) and another measure taken as criteria (EDI). The solutions proposed by the factorial exploratory analysis have been tested by confirmatory analysis using the 2 index of adjustment: the GFI ("Goodness of Fit Index") and the CFI (Comparative Index of Bentler) which, greater than 0.85, shows a satisfying adjustment and the RMC (redidue) which has to be less than 0.10 for a satisfying adjustment. Finally, inferential statistical analysis have studied the relations between the weight's category and the total result at the BSQ and the results of the factors sprung from factorial analysis. RESULTS: Correlations between the items of test/re-test BSQ are greater than 0.93. The alpha coefficient is high for the test (0.95) and also for the re-test (0.94). This shows a very good internal consistency between the 34 items of the BSQ. Concerning the EDI, the correlation between the test/re-test are greater than 0.98. The alpha coefficient of Cronbach is high: 0.85 for the test and 0.84 for the re-test. The Pearson's r of the BSQ/EDI test and the BSQ/EDI re-test greater than 0.7 point out the concomitant validity of the BSQ with the EDI. We made a factorial analysis of the BSQ (test) on the 242 subjects. We used the extraction of the main components method with the extraction's rule of the curve for the real values. The transformation method used here is the normalised Varimax. The factorial analysis shows four factors with their own value greater or equal to 1 (15.1; 1.77; 1.48; 1.08). This solution concerning these four factors explains 55.2% of the total variance. The oblical rotations analysis of the four factors seems to point out a high correlation between these latters (from 0.54 to 0.77), this suggests a hierarchical pattern with a single factor which is confirmed with an Cronbach's alpha of 0.95. Then, we chose to gather around each selected factors the items presenting a substantial saturation, greater than or equal to 0.5 and which are saturated by only one factor. The first factor obtained by the factorial analysis of the BSQ has been called "social avoidance and shame of the exposure of the body". The internal coherence of this factor is satisfactory (Cronbach's alpha = 0.87). The second factor obtained has been called "body dissatisfaction compared to the lower parts ot the body (Cronbach's alpha = 0.90). The third factor has been called "using laxatives and vomiting in order to reduce body dissatisfaction" The fourth factor has been called "unsuited cognitions and behaviours in order to control the weight (Cronbach's alpha = 0.76). The solution with 1 and 4 factors has been tested by a confirmatory analysis. The adjustment parameters of the unifactorial pattern were not satisfactory (GFI = 0.76, CFI = 0.83, RMC = 0.5). The 4 factors pattern adjusted better to the data (GFI = 0.86, CFI = 0.90, RMC = 0.5). In order to determinate the differences between the weight/score categories to the BSQ) score in comparison to the 4 factors (coming from the factorial analysis), several Anova have been released as well as post-hoc tests (test of Sheffé). There is a significant effect of the weight category on the corporal dissatisfaction (BSQ result), F (2.230) = 11.34; p < 0.0001. Scheffe's test placed in a prominent position the fact that the subjects having an overweight (99.85 +/- 31.34) have a corporal dissatisfaction significantly greater than the subjects having a normal weight (74.08 +/- 27.94) and presenting a thinness (63.19 +/- 23.61). We pointed out a significant effect of the weight category on factor one "social avoidance and shame of the exposure of the body" [F (2.232) = 20.18; p < 0.001], on factor 2 "body dissatisfaction compared to the lower parts of the body" [F (2.232) = 6.38; p < 0.005] and factor 4 "reduce body dissatisfaction and unsuited cognitions and behaviours in order to control the weight" [F (2.232) = 5.67; p < 0.005]. However, there is no effect in the weight category for factor 3 "using laxatives and cominting in order to reduce the corporal dissatisfaction" [F (2.232) = 5.67; p > 0.05]. Sheffe's test highlighted the fact that the subjects having overweight have a result more important than the ones having a normal weight and presenting a thinness for factor 1.2 and 4. DISCUSSION: The BSQ "French version" seems in fact to present the same metrical qualities than its original Anglo-Saxon and Spanish versions. The concluding results invite us to continue our study of the BSQ including in our patients, the bulimic subjects and the ones who are worried about corporal aspect. Its implications on the clinical field could be really interesting especially on people suffering from the eating disorders. Then, the BSQ could provide us a way to explore the role of an extreme worry of the body's appearance in the development, the maintenance and the treatment of the eating disorders.

Adult↗
PubMed2006

Danish version of the Oswestry Disability Index for patients with low back pain. Part 1: Cross-cultural adaptation, reliability and validity in two different populations.

Over the past 10 years, a plethora of back-specific patient-orientated outcome measures have appeared in the literature. Standardisation has been advocated by an expert panel of researchers proposing a core set of instruments. Of the condition-specific questionnaires the Oswestry Disability Index (ODI) is recommended for use with low back pain (LBP) patients. To date, no Danish version of the ODI exists which has been cross-culturally adapted, validated and published in the peer-reviewed literature. A cross-cultural adaptation and validation of the ODI for the Danish language was carried out according to established guidelines: 233 patients [half of the patients were seen in the primary sector (PrS) and half in the secondary sector (SeS) of the Danish health care system] with LBP and/or leg pain completed a questionnaire booklet at baseline, 1 day or 1 week and 8 weeks follow-up. The booklet contained the Danish version of the ODI, along with the Roland Morris Disability Questionnaire, the LBP Rating Scale, the SF36 (physical function and bodily pain scales) and a global pain rating. For the ODI test-retest analysis (93 stable patients) resulted in an intraclass correlation coefficient of 0.91, a mean difference of 0.8 and 95% limits of agreements of - 11.5 to + 13. Thus, a worsening greater than 12 points and improvement greater than 13 points can be considered a "real" change above the measurement error. A substantial floor effect was found in PrS patients (14.1%). The ODI showed satisfactory cross-sectional discriminant validity when compared to the external measures. Concurrent validity of the ODI revealed: (a) a 10% and 21% lower ODI score compared to the disability and pain measures, respectively, (b) a poorer differentiation of patient disabilities and (c) an acceptable individual ODI score level compared to the external measures. Longitudinal external construct validity showed moderate correlations (range 0.56-0.78). We conclude that the Danish version of the ODI is both a valid and reliable outcome instrument in two LBP patient populations. The ODI is probably most appropriate for use in SeS patients.

Adolescent↗
PubMed2005

Psychometric field study of the new haemophilia quality of life questionnaire for adults: the 'Hemofilia-QoL'.

Although there is a worldwide interest in the assessment of health-related quality-of-life (HRQoL) in haemophilia patients, no non-disease specific instruments (for adults) are readily available. In this paper, a haemophilia-specific quality-of-life assessment measure for adults (the Hemofilia-QoL questionnaire) has been developed and tested for psychometric properties in 121 adults with haemophilia living in Spain. The Hemofilia-QoL questionnaire is a self-report modular instrument that assesses nine relevant HRQoL domains for patients with haemophilia (e.g. physical health, daily activities, joint damage, pain, treatment satisfaction, treatment difficulties, emotional functioning, mental health, relationships and social activity). Psychometric examination involved the assessment of data quality, scaling assumptions, reliability (internal consistency and test-retest) and validity (concurrent; external clinical criterion and sensitivity). The Hemofilia-QoL 36-item version questionnaire had acceptable internal consistency and retest reliability values. The questionnaire shows excellent concurrent validity (with the SF-36 Health Survey) and external clinical criterion validity (haemophilia clinical status) and sensitivity (health status changes) as well. The Hemofilia-QoL is now available for adult assessment and is ready for use in clinical research in Spain.

Adolescent↗
PubMed2001

[Roaming through methodology. XXXIV. Limitations of predictive models].

Predictive models can be readily used within the populations in which they were developed but they often give a less than satisfactory performance when applied to another population. The main cause of this poorer performance is the fact that predictive models are often developed and evaluated within one single population. In a lot of cases, the model includes too many predictors (or a small population is used), which increases the chance of overfitting. Both external and internal validation techniques have been developed to evaluate predictive models. The most stringent test is an external validation: the application of the model to a new population. The usability of a predictive model can be evaluated using the receiver operating characteristic (ROC) curve.

Data Interpretation, Statistical↗
PubMed1999

The development, validation, and application of a video-based technique for measuring an everyday risk-taking behavior: drivers' speed choice.

Drivers' choice of speed is an important aspect of everyday risk-taking behavior because it has been shown to be one of the most important predictors of road accident involvement. This research developed, validated, and applied a measure of drivers' speed choice that combined a high degree of experimental control with external and ecological validity. In Study 1, a video-simulation measure of drivers' speed choice was developed and found to relate specifically to speed-related accident involvement, implying a degree of external validity. In Study 2, the measure was used to investigate the effect of auditory feedback on drivers' speed choice. It was found that increasing the level of internal car noise decreased drivers' preferred speeds. Further analyses indicated that this was likely due to perceptual effects on speed estimation. Results are discussed in terms of road safety and the ability of video-based measures to facilitate experimental control over tasks involving complex ecological stimuli.

Acceleration↗
PubMed1999

[Development of the Japanese version of the Buss-Perry Aggression Questionnaire (BAQ)].

The Aggression Questionnaire (Buss & Perry, 1992) has been used to investigate links between personality factors and health outcomes. We developed the Japanese version of the Buss-Perry Aggression Questionnaire (BAQ) and assessed validity and reliability of the scale. Study I (N = 1,125 college students) used a 45-item rating questionnaire measuring each of four components of aggression: Anger, Hostility, Physical Aggression, and Verbal Aggression. Four aggression subscales emerged clearly from exploratory factor analysis. Study II (N = 611 college students) used a 24-item questionnaire and replicated factor structure and factor loadings of Study I. The scales were shown to be highly internally consistent, and stable at appropriate levels over 4-month time period. Normative data, factorial validity, and external evidence of construct, convergent, and discriminant validity for the scales were also presented.

Adult↗
PubMed2006

Vascular depression: A distinct diagnostic subtype?

Vascular depression has been proposed as a unique and valid diagnostic subtype on the basis of studies of external (concurrent and predictive) validity. Validating a diagnostic entity on the basis of external validity is problematic, because it presupposes that the construct is well defined (i.e., the proposed features cluster together to define a distinct patient group). Because such evidence has not been obtained, we propose that the next critical step in evaluating this potential subtype is to establish internal (construct) validity and highlight taxometric analysis and latent class cluster analysis as illustrative multivariate statistical techniques that can be used in this effort. The psychometric approach advocated here (despite its inherent assumptions and limitations) might substantially improve on previous diagnostic efforts (e.g., expert consensus), and vascular depression might serve as a prototype for future psychiatric classification.

Cerebrovascular Disorders↗
PubMedDate not supplied

Criteria for evaluating the significance of developmental research in the twenty-first century: force and counterforce.

Since its birth approximately 100 years ago, the field of child development has undergone fluctuations in the criteria used to determine which research topics are more or less worthy of study. The purpose of this paper is to identify the forces that influence how developmental research is prioritized and evaluated and how these influences are changing as we enter the new millennium. We do so by considering the developmental researcher in context and suggest that there will be increasing pressure to use new criteria when assessing the significance of twenty-first-century developmental science. We review the three most commonly used forms of research validity--internal, external, and ecological--and then identify new research validities that we believe are likely to play increasingly important roles in the next millennium. We also argue that many developmental scientists will increasingly be pressured by forces that are external to the traditional research environment and that these forces will shape the ways in which the significance of developmental research is evaluated.

Child↗
PubMedDate not supplied

A review of methodologies for assessing drug effectiveness and a new proposal: randomized database studies.

The need to evaluate the effects of health technologies in clinical practice is increasingly important. In this article, we review the advantages and limitations of naturalistic randomized clinical trials (RCTs) and database analyses, the two primary methods for evaluating treatment effectiveness. Also, we comment on a newer research strategy, cross-design synthesis, which proposes the complementary use of both experimental RCTs and observational database methodologies to avoid the main weaknesses of each: respectively, the lack of external and internal validity. Finally, we propose a new strategy--randomized database studies--capable of generating results with an acceptable balance between internal and external validity. This strategy consists of the simultaneous use of both experimental and observational tools in the assessment of drugs' effectiveness. Randomization is essential to minimize comparison bias, and one possibility for such studies is that randomization modules could be included in computer-based patient records. Although we identify some of the difficulties in implementing the process, the progressive standardization of clinical practice and the development and widespread adoption of improved computer-based patient records could facilitate the use of randomized database studies as a new method of research.

Economics, Pharmaceutical↗
PubMedDate not supplied

Statistical aspects of clinical trials of antibiotics in acute infections.

Controlled clinical trials are important tools for evaluating antibiotics in acute infections. External and internal validity, definition of efficacy criteria, and size of the patient sample constitute special statistical problems in such studies. Critical issues regarding external validity pertain to the selection of patients and to the concept of consecutive patients. The internal validity of a study is influenced by the withdrawal of patients from the evaluation after randomization and the comparability of treatment groups with regard to prognostic factors. The definition of efficacy criteria on the basis of bacteriologic outcomes across control visits is not straightforward. Particularly, the evaluation of efficacy at the last follow-up visit must take into account the accumulated information rather than the cross-sectional information. The most common situation in comparative trials of antibiotics is that rather small differences in efficacy can be anticipated. Sometimes, the question at issue is the demonstration of antibiotic equivalence. For valid conclusions to be made in such situations, large samples must be used. A basic problem affecting many studies of antibiotics is that this criterion is not fulfilled.

Acute Disease↗
PubMedDate not supplied

Statistically validated QSARs, based on theoretical descriptors, for modeling aquatic toxicity of organic chemicals in Pimephales promelas (fathead minnow).

The use of Quantitative Structure-Activity Relationships in assessing the potential negative effects of chemicals plays an important role in ecotoxicology. (LC50)(96h) in Pimephales promelas (Duluth database) is widely modeled as an aquatic toxicity end-point. The object of this study was to compare different molecular descriptors in the development of new statistically validated QSAR models to predict the aquatic toxicity of chemicals classified according to their MOA and in a unique general model. The applied multiple linear regression approach (ordinary least squares) is based on theoretical molecular descriptor variety (1D, 2D, and 3D, from DRAGON package, and some calculated logP). The best combination of modeling descriptors was selected by the Genetic Algorithm-Variable Subset Selection procedure. The robustness and the predictive performance of the proposed models was verified using both internal (cross-validation by LOO, bootstrap, Y-scrambling) and external statistical validations (by splitting the original data set into training and validation sets by Kohonen-artificial neural networks (K-ANN)). The model applicability domain (AD) was checked by the leverage approach to verify prediction reliability.

Animals↗
PubMed2005

Scholarly literature review: Efficacy of psychological interventions for pediatric chronic illnesses.

OBJECTIVE: To review empirical studies of the efficacy of psychological interventions as adjuvant therapies for children with pediatric diabetes, cancer, cystic fibrosis, and sickle cell disease. METHODS: A search was conducted for qualifying studies published since 1980. Only studies meeting basic criteria for external and internal validity were included. Nineteen studies were identified, providing data on 62 outcome variables. Effect sizes (ESs) were analyzed by illness type, intervention type, and strength of internal and external validity of the research design. RESULTS: Overall, interventions were associated with large ESs, which were not significantly moderated by illness type or intervention type. However, larger ESs were associated with lower scores on validity of research design. CONCLUSIONS: Adjuvant psychological interventions for pediatric chronic illnesses appear in general to be efficacious, associated with a large mean ES across a range of outcome variables. However, until more studies have been completed using stronger research designs, only tentative conclusions can be drawn.

Adaptation, Psychological↗
PubMed2004

Preoperative probability model for predicting overall survival after resection of pulmonary metastases from colorectal cancer.

BACKGROUND: The aim of this study was identify readily available factors most helpful in predicting survival and to develop a prognostic nomogram for patients with pulmonary metastases from colorectal cancer who are candidates for thoracotomy. METHODS: Pretreatment data on 313 patients with metastases who underwent thoracotomy were analysed. Fourteen preoperative clinical and pathological variables were used to develop a probability model, in which their association with 3-year survival was tested. A nomogram to predict median, 1- and 3-year survival was constructed and validated internally using the concordance index (c-index). The nomogram was then validated with an external data set. RESULTS: Five variables were identified as independent predictors of 3-year survival: prethoracotomy carcinoembryonic antigen level, number of pulmonary tumours, presence of hilar or mediastinal tumour-infiltrated lymph nodes, histology of the primary tumour and presence of extrathoracic disease. The nomogram was well calibrated for predicting 3-year overall survival. The internal validated c-index of the nomogram was 0.72. Applied to another data set, the external validated c-index was 0.66. CONCLUSION: This model has moderate predictive ability to discriminate between patients who are likely to survive after thoracotomy for pulmonary metastases from colorectal cancer.

Adult↗
PubMed1998

Randomized database studies: a new method to assess drugs' effectiveness?

The need to evaluate drugs' effects in real clinical practice is increasingly important. Randomized clinical trials (RCTs) and database analyses (DBA) are the two main methods to assess treatments effectiveness. RCTs remain the "gold standard" for comparing alternative treatments. However, they are conducted under strict, protocol-driven conditions that may limit their generalizability. Advantages of new high quality clinical databases, on the other hand, include the simple and economic access to large number and range of cases, and the ability to capture all aspects of actual medical practice. The main potential limitation of DBA is the potential for comparison bias due to the lack of randomization. Despite the efforts to design naturalistic trials and to use sophisticated statistical techniques to minimize selection bias, the inherent limitations of both methods (problems of external and internal validity, respectively) have not been completely solved. Thus, the actual challenge is the development of some new strategy capable of generating results with an acceptable balance between internal and external validity. As randomization is essential to minimize comparison bias, we point out the possibility to include randomization modules in computer-based patient records. The theoretical foundation of these "randomized database studies" is the simultaneous use of both experimental and observational methods in the assessment of drugs' effectiveness. The progressive standardization of clinical practice and the development and adoption of improved computer-based patient records could facilitate the use of this new research strategy.

Databases, Factual↗
PubMed2003

Megavariate data analysis of mass spectrometric proteomics data using latent variable projection method.

There are many data mining techniques for processing and general learning of multivariate data. However, we believe the wavelet transformation and latent variable projection method are particularly useful for spectroscopic and chromatographic data. Projection based methods are designed to handle hugely multivariate nature of such data effectively. For the actual analysis of the data we have used latent variable projection methods such as principal component analysis (PCA) and partial least squares projection to latent structures based discriminant analysis (PLS-DA) to analyze the raw data presented to the participants of the First Duke Proteomics Data Mining Conference. PCA was used to solve problem #1 (clustering problem) and the PLS-DA was used to solve problem #2 (classification problem). The idea of internal and external cross-validation was used to validate the model obtained from the classification analysis. The simple two-component PLS-DA model obtained from the analysis performed well. The model has completely separated the two groups from all the data. The same model applied on two-thirds of the data showed good performance by external validation with independent test set of remaining 13 specimens obtained by setting aside the spectra of every third specimen (accuracy of 85%).

Artificial Intelligence↗
PubMed2026

Crucial role of telomere maintenance-related genes in survival prediction and subtype identification in colorectal cancer.

BACKGROUND: Telomere maintenance-related genes (TMRGs) are implicated in Colorectal cancer (CRC) development, but their prognostic value and clinical relevance remain insufficiently explored. This study aims to develop a TMRG-based prognostic model and elucidate its clinical utility in CRC management. METHODS: The Cancer Genome Atlas database was utilized to download RNA-seq data from 638 CRC and 51 control samples. Differential expressed genes were screened and intersected with 2086 TMRGs, resulting in the identification of 976 TMRGs. Through univariate and multivariate Cox regression analysis, a prognostic model comprising three telomere maintenance-related biomarkers (PDE1B, TFAP2B, and HSPA1A) was developed and validated using an external dataset. By integrating the model risk score with clinical features, a nomogram was constructed to predict the survival outcomes of CRC patients. Additionally, an in-depth investigation of the immuno-infiltration, functional variation and drug sensitivity analysis were performed in two risk subgroups defined by the prognostic model. Finally, the functional significance of PDE1B in CRC cell lines was investigated through MTT assays, cell colony formation assays, transwell assays and flow cytometry. RESULTS: A total of 976 DE-TMRGs were enriched in telomere/DNA replication pathways. A three-gene signature (PDE1B, TFAP2B, and HSPA1A) stratified patients into high- and low-risk groups with divergent survival (AUC >0.60, validated externally). High-risk patients had advanced N/M stages, elevated M0/M2 macrophages, reduced CD4+ memory T cells, and upregulated immune checkpoints. Nomogram integrating risk score, age, and N/M stage accurately predicted 1-/3-/5-year survival. Low-risk patients showed greater 5-fluorouracil sensitivity. PDE1B expression was significantly reduced in CRC tissues and correlated with advanced stages. Functional assays confirmed PDE1B overexpression suppressed proliferation, migration, invasion, and induced apoptosis in CRC cells. CONCLUSION: This study identifies a moderately predictive telomere maintenance-related gene signature as an independent prognostic predictor in CRC. The risk stratification model effectively discriminates patients with distinct survival patterns, tumor microenvironments, and therapeutic responses, while the integrated nomogram offers additional reference information for survival analysis, albeit with only moderate predictive accuracy. These findings indicate telomere maintenance-related gene signature could serve as a preliminary auxiliary risk stratification tool for postoperative CRC patients, PDE1B may also serve as a potential epithelial tumor-suppressor target for future preclinical studies.

PDE1B↗