Assessment Of Colorectal Cancer Research Articles

Integrating transcriptomics and machine learning for immunotherapy assessment in colorectal cancer

Colorectal cancer (CRC) is a highly prevalent and lethal malignancy worldwide. Although immunotherapy has substantially improved CRC outcomes, intolerance remains a major concern among most patients. Considering the pivotal role of the tumor microenvironment (TME) in tumor progression and treatment outcomes, profiling the TME at the transcriptomic level can provide novel insights for developing CRC treatment strategies. Seventy-seven TME-associated signatures were acquired from previous studies. To elucidate variations in prognosis, clinical features, genomic alterations, and responses to immunotherapy in CRC, we employed a non-negative matrix factorization algorithm to categorize 2595 CRC samples of 27 microarrays from the Gene Expression Omnibus database. Three machine learning techniques were employed to identify a signature specific to immunotherapy. Subsequently, the mechanisms by which this signature interacts with TME subtypes and immunotherapy were investigated. Our findings revealed five distinct TME subtypes (TMESs; TMES1–TMES5) in CRC, each exhibiting a unique pattern of immunotherapy response. TMES1, TMES4, and TMES5 had relatively inferior outcomes, TMES2 was associated with the poorest prognosis, and TMES3 had a superior outcome. Subsequent investigations revealed that activated dendritic cells could enhance the immunotherapy response rate, with their augmentation effect closely associated with the activation of CD8+T cells. We successfully classified CRC into five TMESs, each demonstrating varying response rates to immunotherapy. Notably, the application of machine learning to identify activated dendritic cells helped elucidate the underlying mechanisms contributing to these differences. We posit that these TMESs hold promising clinical implications for prognostic evaluation and guidance of immunotherapy strategies, thereby providing valuable insights to inform clinical decision-making.

Role of artificial intelligence in risk prediction, prognostication, and therapy response assessment in colorectal cancer: current state and future directions.

Artificial Intelligence (AI) is a branch of computer science that utilizes optimization, probabilistic and statistical approaches to analyze and make predictions based on a vast amount of data. In recent years, AI has revolutionized the field of oncology and spearheaded novel approaches in the management of various cancers, including colorectal cancer (CRC). Notably, the applications of AI to diagnose, prognosticate, and predict response to therapy in CRC, is gaining traction and proving to be promising. There have also been several advancements in AI technologies to help predict metastases in CRC and in Computer-Aided Detection (CAD) Systems to improve miss rates for colorectal neoplasia. This article provides a comprehensive review of the role of AI in predicting risk, prognosis, and response to therapies among patients with CRC.

Downregulation of LRRC19 Is Associated with Poor Prognosis in Colorectal Cancer

Objective Colorectal cancer (CRC) is globally one of the most often diagnosed cancers with high mortality rates. This study aimed to explore novel biomarkers for the diagnosis and prognosis of CRC. Methods We collected 4 datasets about CRC in GEO and sought differentially expressed genes (DEGs) with GEO2R. Leucine-rich repeat-containing protein 19 (LRRC19) expression was assessed through the Oncomine and TIMER database analyses, which was further confirmed by qRT-PCR of CRC samples. We used online survival analysis tools (GEPIA, PrognoScan, and Kaplan–Meier plotter) to examine the prognostic value of LRRC19 in CRC and other malignancies. GO and KEGG enrichment analyses were employed to explore the biological functions of LRRC19. Finally, we conducted network prediction by STRING and further validation on the GEPIA to discover other molecules that might interact with LRRC19. Results A total of 21 upregulated and 46 downregulated DEGs were identified from the 4 datasets. The TIMER and Oncomine online analyses showed lower mRNA of LRRC19 in CRC tissues compared with adjacent normal tissues, which was validated by qRT-PCR in CRC patient samples. The survival analysis through the GEPIA and PrognoScan websites revealed that low LRRC19 expression was significantly correlated with poor prognosis in CRC patients. The Kaplan–Meier plotter survival analysis indicated that low LRRC19 expression was significantly associated with the disease progression of patients with ovarian cancer, gastric cancer, breast cancer, and lung cancer. The enrichment analysis suggested that low expression of LRRC19 could be involved in the retinol metabolism and the zymogen granule membrane. Through STRING and GEPIA, it was found that LRRC19 is clearly associated with ZCCHC10, MOB3B, IMMP2L, and TRMT11. Conclusion LRRC19 mRNA was prominently decreased in human CRC tissues and was significantly associated with shorter survival in CRC patients. LRRC19 might serve as a possible target for early diagnosis and prognosis assessment in CRC.

Finding Waldo: The Evolving Paradigm of Circulating Tumor DNA (ctDNA)-Guided Minimal Residual Disease (MRD) Assessment in Colorectal Cancer (CRC).

Simple SummaryAfter the surgical removal of colorectal cancer (CRC), residual cancer cells undetectable by standard blood tests and imaging studies are responsible for cancer recurrence. Currently, chemotherapy is often administered after surgery to eradicate residual cancer cells, a decision guided by clinical and pathologic criteria, which are imprecise. Circulating tumor DNA (ctDNA) consists of DNA fragments in the bloodstream derived from cancer cells, and the presence of ctDNA likely indicates the presence of residual cancer cells. The current article discusses how ctDNA technology can help guide treatment in patients with CRC after curative surgery.Circulating tumor DNA (ctDNA), the tumor-derived cell-free DNA fragments in the bloodstream carrying tumor-specific genetic and epigenetic alterations, represents an emerging novel tool for minimal residual disease (MRD) assessment in patients with resected colorectal cancer (CRC). For many decades, precise risk-stratification following curative-intent colorectal surgery has remained an enduring challenge. The current risk stratification strategy relies on clinicopathologic characteristics of the tumors that lacks precision and results in over-and undertreatment in a significant proportion of patients. Consequently, a biomarker that can reliably identify patients harboring MRD would be of critical importance in refining patient selection for adjuvant therapy. Several prospective cohort studies have provided compelling data suggesting that ctDNA could be a robust biomarker for MRD that outperforms all existing clinicopathologic criteria. Numerous clinical trials are currently underway to validate the ctDNA-guided MRD assessment and adjuvant treatment strategies. Once validated, the ctDNA technology will likely transform the adjuvant therapy paradigm of colorectal cancer, supporting ctDNA-guided treatment escalation and de-escalation. The current article presents a comprehensive overview of the published studies supporting the utility of ctDNA for MRD assessment in patients with CRC. We also discuss ongoing ctDNA-guided adjuvant clinical trials that will likely shape future adjuvant therapy strategies for patients with CRC.

Circulating tumor DNA (ctDNA) as a minimal residual disease (MRD) assessment and recurrence risk in patients undergoing curative intent resection with or without adjuvant chemotherapy in colorectal cancer: A systematic review and meta-analysis.

3623 Background: Minimal residual disease (MRD) assessment may effectively detect cure in patients with colorectal cancer (CRC). Emerging data have suggested that circulating tumor DNA (ctDNA) can be a reliable biomarker for MRD in patients. Recent studies have shown the ability to detect MRD using ctDNA assay to assess recurrence risk and patient selection for adjuvant chemotherapy. We performed a systematic review and metanalysis of post operative ctDNA in Stage I-IV (oligometastatic) CRC patients after curative intent resection with or without adjuvant chemotherapy. Methods: We searched PubMed/Medline, EMBASE, Web of Science, Cochrane Library, and Google from inception to February 3, 2022 using keywords related to colorectal cancer, ctDNA, and MRD. The search also includes paper and conference presentations. The search resulted in 427 studies after removing the duplicates. Data were extracted to perform a meta-analysis using RevMan 5.4. software. Subsequent subgroup analysis was performed for stages I-III and oligometastatic stage IV CRC patients. Results: After the initial abstract screening, 48 studies were identified. The final review led to the inclusion of 27 studies representing 3459 patients with evaluable ctDNA, with 623 having +ve post-surgery ctDNA levels. Seven studies had analyses of patients specifically with oligometastatic disease, the rest 20 studies subdivided within stages I-III. The pooled HR for RFS in post-surgical ctDNA +ve vs -ve patients in all stages was 7.16 (95% CI 6.12-8.36) p <0.00001. Subgroup analysis revealed pooled HR = 8.27 (95% CI 6.16-11.09) and 6.07 (95% CI 4.54-8.13) for stage I-III and IV CRC, respectively. Only 11 studies did analysis for post adjuvant chemotherapy patients based on ctDNA status. The pooled HR for RFS in post-adjuvant chemotherapy ctDNA +ve versus -ve patients in all stages was 12.40 (95% CI 9.24-16.64) p <0.00001. Subgroup analysis revealed pooled HR = 13.95 (95% CI 9.08-21.43) and 11.39 (95% CI 5.99-21.66) for stage I-III and IV CRC, respectively. Conclusions: This is the largest and most current meta-analysis done on ctDNA levels as MRD assessment in CRC. Our analysis emphasizes that post operative ctDNA is a strong prognostic marker of RFS. Based on our results ctDNA can be a significant and independent predictor of RFS. Several ctDNA-based randomized adjuvant trials are ongoing internationally to confirm the clinical utility of ctDNA in colorectal cancer. [Table: see text]

A model of multiple tumor marker for lymph node metastasis assessment in colorectal cancer: a retrospective study.

BackgroundAssessment of colorectal cancer (CRC) lymph node metastasis (LNM) is critical to the decision of surgery, prognosis, and therapy strategy. In this study, we aimed to develop and validate a multiple tumor marker nomogram for predicting LNM in CRC patients.MethodsA total of 674 patients who met the inclusion criteria were collected and randomly divided into primary cohort and internal test cohort at a ratio of 7:3. An external test cohort enrolled 178 CRC patients from the West China Hospital. Clinicopathologic variables were obtained from electronic medical records. The least absolute shrinkage and selection operator (LASSO) and interquartile range analysis were carried out for variable dimensionality reduction and feature selection. Multivariate logistic regression analysis was conducted to develop predictive models of LNM. The performance of the established models was evaluated by the receiver operating characteristic (ROC) curve, calibration belt, and clinical usefulness.ResultsBased on minimum criteria, 18 potential features were reduced to six predictors by LASSO and interquartile range in the primary cohort. The model demonstrated good discrimination and ROC curve (AUC = 0.721 in the internal test cohort, AUC = 0.758 in the external test cohort) in LNM assessment. Good calibration was shown for the probability of CRC LNM in the internal and external test cohorts. Decision curve analysis illustrated that multi-tumor markers nomogram was clinically useful.ConclusionsThe study proposed a reliable nomogram that could be efficiently and conveniently utilized to facilitate the assessment of individually-tailored LNM in patients with CRC, complementing imaging and biopsy tests.

Postoperative mortality risk assessment in colorectal cancer: development and validation of a clinical prediction model using data from the Dutch ColoRectal Audit.

BackgroundAs the outcome of modern colorectal cancer (CRC) surgery has significantly improved over the years, however, renewed and adequate risk stratification for mortality is important to identify high-risk patients. This population-based study was conducted to analyse postoperative outcomes in patients with CRC and to create a risk model for 30-day mortality.MethodsData from the Dutch Colorectal Audit were used to assess differences in postoperative outcomes (30-day mortality, hospital stay, blood transfusion, postoperative complications) in patients with CRC treated from 2009 to 2017. Time trends were analysed. Clinical variables were retrieved (including stage, age, sex, BMI, ASA grade, tumour location, timing, surgical approach) and a prediction model with multivariable regression was computed for 30-day mortality using data from 2009 to 2014. The predictive performance of the model was tested among a validation cohort of patients treated between 2015 and 2017.ResultsThe prediction model was obtained using data from 51 484 patients and the validation cohort consisted of 32 926 patients. Trends of decreased length of postoperative hospital stay and blood transfusions were found over the years. In stage I–III, postoperative complications declined from 34.3 per cent to 29.0 per cent (P < 0.001) over time, whereas in stage IV complications increased from 35.6 per cent to 39.5 per cent (P = 0.010). Mortality decreased in stage I–III from 3.0 per cent to 1.4 per cent (P < 0.001) and in stage IV from 7.6 per cent to 2.9 per cent (P < 0.001). Eight factors, including stage, age, sex, BMI, ASA grade, tumour location, timing, and surgical approach were included in a 30-day mortality prediction model. The results on the validation cohort documented a concordance C statistic of 0.82 (95 per cent c.i. 0.80 to 0.83) for the prediction model, indicating good discriminative ability.ConclusionPostoperative outcome improved in all stages of CRC surgery in the Netherlands. The developed model accurately predicts postoperative mortality risk and is clinically valuable for decision-making.

Minimal residual disease assessment in colorectal cancer (MiRDA-C).

TPS236 Background: Detection of circulating tumor DNA (ctDNA) in the bloodstream is emerging as a novel marker for identifying of radiographically occult microscopic or minimal residual disease (MRD) in colorectal cancer (CRC) patients (pts) after curative intent treatments. Accumulating data suggest that ct-DNA defined MRD is a highly specific prognostic biomarker for future recurrences with a lead time of several months and prospective clinical trials are being conducted using ct-DNA defined MRD as an integral biomarker for improving risk stratification for adjuvant chemotherapy decision making. However, large scale, prospective data regarding kinetics of ctDNA-defined MRD with accurate pre-analytical methodology for plasma isolation and paired clinical data are limited. Methods: In this multi-center, prospective observational study, 1,000 pts with resectable CRC (stages II – IV) without other active malignancies undergoing therapy with curative intent will be enrolled any time from time of diagnosis up to start of adjuvant therapy (or ≤ 3 months post curative surgery, whichever is earlier). All therapeutic and surveillance visits decisions are at the discretion of the treating physicians. Serial biospecimens including blood (in Cell-Free DNA BCT tubes) to be processed to plasma and buffy coat in ≤ 2 days and formalin fixed tumor tissue will be collected at key time points until the time of radiographic recurrence or up to 5 years of surveillance. Blood draws will be at study entry, after each line of neoadjuvant therapy, post-surgery, during and after adjuvant therapy in addition to each surveillance visit. These blood draws will be coordinated with pts’ standard of care visits in order to minimize additional venipunctures. Relevant clinical data including demographics, cancer history, treatment details and outcomes, serum tumor markers and genomic data will be collected at each time point. Samples will be evaluated retrospectively with a primary objective of evaluating sensitivity and specificity of post-operative MRD for radiographic recurrences utilizing Guardant Health’s Reveal assay. Other key objectives include evaluating ctDNA kinetics with neoadjuvant and adjuvant therapies and to correlate with outcomes. The study is active, and enrollment is ongoing. Clinical trial information: NCT04739072.

Prognostic Impact of Tumor Budding on Moroccan Colon Cancer Patients.

Background Tumor budding is now emerging as one of the robust and promising histological factors that play an important role in colon cancer. In this study, we aimed to investigate the association between tumor budding and tumor clinicopathological factors, tumor molecular signature, and patient survival for the first time in a Moroccan population. Methods We collected data of 100 patients operated from colon adenocarcinoma. Tumor budding was assessed on HES slides, according to the International Tumor Budding Consensus Conference 2016 recommendations. The expression of MMR proteins was performed by immunohistochemistry. KRAS and NRAS mutations testing was performed by Sanger sequencing and pyrosequencing. Results High tumor budding grade (BUD 3) was found to be significantly associated with adverse clinicopathological features including older age (P=0.03), presence of perineural invasion (P=0.02), presence of vascular invasion (P=0.05), distant metastases (P < 0.001), advanced TNM stage (P=0.001), the occurrence of relapse (P=0.04), and the high number of deceased cases (P=0.02). Interestingly, we found that tumors with high-grade tumor budding were more likely to be microsatellite stable (MSS) (P=0.005) and harbor more KRAS mutations (P=0.02). Tumors with high-grade tumor budding were strongly associated with KRAS G12D mutation (P=0.007). In all stages, high tumor budding was correlated with poorer overall survival (P=0.04) and decreased relapse-free survival with a difference close to significance ((P=0.09). We concluded that high tumor budding was strongly associated with unfavorable clinicopathological features and special molecular biomarkers and effectively affects the overall survival of CC patients. Conclusions Based on these findings and the ITBCC group recommendations, tumor budding should be taken into account along with other clinicopathologic factors in the risk assessment of colorectal cancer.

Cover Image

The cover image is based on the Original Article Development of a semi-automated method for tumour budding assessment in colorectal cancer and comparison with manual methods by Natalie C. Fisher et al., https://doi.org/10.1111/his.14574

Social-life factors associated with participation in screening and further assessment of colorectal cancer: A nationwide ecological study in Japanese municipalities

The burden of colorectal cancer in developed countries is high, and it is a major public health concern in Japan. Improving the quality of evidence on colorectal cancer screening participation and further assessment participation rates is important to reduce this burden. This study examined the social-life factors that influence colorectal cancer screening programs in Japan, particularly the effects of the proportion of elderly people and social capital, using a municipality-level national database and existing health reports. Data from a national municipality-based study were analyzed to identify social-life factors associated with participation in colorectal cancer screening and further assessment. Administrative data on the Japanese municipal screening programs were drawn from the Report on Regional Public Health Services and Health Promotion Services 2017. Available data used as predictors of interest for all 1719 municipalities as of 2017 were from the national census, statistical reports on the land area by prefecture and municipality, municipal financial surveys, a survey of physicians, dentists and pharmacists, and other databases. The mean rate of participation in colorectal cancer screening was 13.8%, and that of further assessment was 73.6%. Multiple linear regression analyses of the two outcomes showed that the proportion of elderly people was most significantly positively associated with colorectal cancer screening programs (β = 0.51 for participation, β = 0.13 for further assessment participation), and the proportion of single-elderly-person households was most significantly negatively associated (β = −0.45 and −0.19, respectively). It is suggested that the health behaviors required for participation in colorectal cancer programs in Japanese elderly populations are greatly affected by family members.

Are Volatile Organic Compounds Accurate Markers in the Assessment of Colorectal Cancer and Inflammatory Bowel Diseases? A Review.

Simple SummaryEarly diagnosis is crucial for reducing colorectal cancer-related mortality in both the general population and inflammatory bowel disease. Volatile organic compound (VOC) analysis is a promising alternative to the gold standard procedure, endoscopy, for early detection and surveillance of colorectal diseases. This review aimed to provide a general overview of the most recent evidence in this area on VOC testing in breath, stool, and urine samples.Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the Western world. Early detection decreases incidence and mortality. Screening programs based on fecal occult blood testing help identify patients requiring endoscopic examination, but accuracy is far from optimal. Among the alternative strategies, volatile organic compounds (VOCs) represent novel potentially useful biomarkers of colorectal cancer. They also represent a promising tool for the screening of both intestinal inflammation and related CRC. The review is focused on the diagnostic potential of VOCs in sporadic CRC and in inflammatory bowel diseases (IBD), which increase the risk of CRC, analyzing future clinical applications. Despite limitations related to inadequate strength of evidence, differing analytical platforms identify different VOCs, and this unconventional approach for diagnosing colorectal cancer is promising. Some VOC profiles, besides identifying inflammation, seem disease-specific in inflammatory bowel diseases. Thus, breath, urine, and fecal VOCs provide a new and promising clinical approach to differential diagnosis, evaluation of the inflammatory status, and possibly the assessment of treatment efficacy in IBD. Conversely, specific VOC patterns correlating inflammatory bowel disease and cancer risk are still lacking, and studies focused on this issue are strongly encouraged. No prospective studies have assessed the risk of CRC development by using VOCs in samples collected before the onset of disease, both in the general population and in patients with IBD.

The Clinical Utility of Serum CXCR-2 Assessment in Colorectal Cancer (CRC) Patients.

The current study aimed to evaluate the clinical utility of the levels of the C-X-C-motif chemokine receptor-2 (CXCR-2) serum receptor in comparison to the carcinoembryonic antigen (CEA) tumor marker and - the C-reactive protein (CRP) inflammatory marker in the diagnosis and prognosis of colorectal cancer (CRC). Our study comprised 59 patients with CRC and 46 healthy subjects. Serum concentrations of the analyzed proteins were measured using enzyme-linked immunosorbent assay, chemiluminescent microparticle immunoassay and immunoturbidimetric methods. Serum levels of CXCR-2 were lower, while those of CEA and CRP were significantly higher in CRC patients in comparison to the control group. The diagnostic sensitivity of CXCR-2 was higher than that of CEA, and increased when CXCR-2 analysis was combined with CEA or CRP. According to our knowledge, this is the first study concerning the significance of CXCR2 as a CRC biomarker. Measurement of the serum levels of CXCR-2 may improve the diagnosis efficiency of CRC patients, especially in combination with the tumor marker CEA.

Abdominal Ultrasound Compared to MDCT in Assessment of Colorectal Cancer

Background and Aim: Colorectal cancer is the third most common cancer and the fourth most frequent cause of cancer deaths worldwide. The aim of this study to compare the diagnostic performance of abdominal ultrasound and multidetector CT in detection of colorectal cancer. Methods: this study included fifty patients were presented to surgical department of Mit Ghamr oncology center. All patients were examined on MDCT to show presence of the cancer. then examined by abdominal ultrasound to evaluate ability of ultrasound to detect the cancer. Results: fifty patients were included (28 men and 22 women) had a mean age of 47.5years (range 28-70years). Our study results suggested that abdominal ultrasound had sensitivity and specificity in diagnosis of cancer colon were 82.4% and 87.5 % respectively. The accuracy of US was 84%. For MDCT, sensitivity and specificity of cancer colon were 100% and 93.8 respectively. The accuracy of MDCT was 98%. Conclusion: ultrasonography is a useful initial screening tool for colorectal cancer in patients presenting with abdominal distension. Compared with MDCT scanning and other modalities. Ultrasonography is easily available; does not involve radiation, bowel preparation, or sedation; carries no risk of colonic perforation; and is less expensive. Further studies to confirm the usefulness of ultrasonography for diagnosis of colorectal cancer are warranted. CT is valuable in preoperative assessment and staging of colorectal cancer as well as in postoperative surveillance for recurrence. Rapid advances in technology will likely continue to improve the accuracy and usefulness of CT.

Integrating multiple “omics” analyses, on a triage concept, for effective case selection followed by diagnostic colonoscopy.

244 Background: Implementation of population screening for colorectal cancer (CRC) before colonoscopy can reduce the challenge of the overall capacity of bowel examination and improve survival. Blood based CRC assessment biomarkers, on a triage concept, can lead to improved selection to colonoscopy and cost-effective CRC care. Methods: Innovative multi-omics approaches, with global and targeted LCMS data production (metabolomics, lipidomics, and 2D proteomics) and integrative data analytics, were applied to discover serological biomarkers to assess nonadvanced adenoma and identify stage I/II colorectal bowel lesions. A cohort of 2396 normal, 660 adenoma, 953 stage I, and 101 stage II blood samples, was constructed to discover screening biomarkers to support case finding of patients at high risk for nonadvanced adenoma and stage I/II cancer for subsequent diagnostic colonoscopy. Results: A three-analyte mProbe panel was constructed which outperformed the commercial assays of plasma methylated septin 9 and fecal Cologuard tests. Sensitivity: (1) nonadvanced adenoma–Cologuard 17.2%, mProbe 76.0%; (2) stage I-III-Cologuard 93.3%, stage I-II Septin 9 (ARUP laboratories) 77%, stage I-II mProbe: 92.3%. Specificity–Cologuard 89.8%, Septin 9 (ARUP laboratories) 88%, mProbe 90.7%. Conclusions: mProbe triage concept of a blood-based protein biomarker panel promises the precision to allow future CRC screening, and reduce the low-risk utilization of unnecessary, unpleasant and risk-associated bowel examinations.

Evaluation of Staging Laparoscopy in Colorectal Cancer Assessment

Evaluation of Staging Laparoscopy in Colorectal Cancer Assessment

Epithelial-to-mesenchymal transition signature assessment in colorectal cancer quantifies tumour stromal content rather than true transition.

The process of epithelial‐to‐mesenchymal transition (EMT) in cancer is a well‐described process whereby epithelial tumour cells undergo molecular/phenotypic changes and transition to a mesenchymal biology. To aid in the transcriptional characterisation of this process, gene expression signatures have been developed that attribute a relative EMT score to samples in a given cohort. We demonstrate how such EMT signatures can identify epithelial cell line models with high levels of transition but also highlight that, unsurprisingly, fibroblast cell lines, which are inherently mesenchymal, have a higher EMT score relative to any epithelial cell line studied. In line with these data, we demonstrate how increased tumour stromal composition, and reduced epithelial cellularity, significantly correlates with increasing EMT signature score, which is evident using either in silico subtyping analysis (p < 0.00001) or in situ histopathological characterisation (p < 0.001). Considered together, these results reinforce the importance not only of interdisciplinary research to correctly define the nature of EMT biology but also the requirement for a cadre of multidisciplinary researchers who can analyse and interpret the underlying pathological, bioinformatic and molecular data that are essential for advancing our understanding of the malignant process. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Potential role of MicroRNA 200c gene expression in assessment of colorectal cancer

Background and aimColorectal cancer (CRC) is a common cancer worldwide that affects men and women of all racial and ethnic groups. Recent evidence supports the role of microRNAs in CRC. We planned to investigate microRNA200c expression and its relation with diagnosis, prognosis, metastasis and overall survival in CRC patients. This study enrolled 90 subjects (3’0 CRC patients, 30 patients with benign colorectal polyps and 30 healthy control subjects). MethodsLaboratory investigations included measurement of serum CA19-9 and CEA by enzyme linked immunosorbent assay (ELISA) method and relative quantitation (RQ) of microRNA200c gene expression by real time PCR technique. ResultsSignificant higher MicroRNA200c expression levels in CRC patients versus both benign (P < 0.011) and control groups (P < 0.001), additionally, benign group had elevated levels versus control (P < 0.001). MicroRNA 200c at cutoff >4.56 had sensitivity 86.67% and specificity 73.33% (P < 0.001) for CRC discrimination. Kaplan-Meier survival analysis revealed significant association (P = 0.028) of high expression of microRNA200c with decreased overall survival. ConclusionNoticeable up-regulation of microRNA200c in CRC and its remarkable relation with unfavorable survival suggesting its potential dual use as a diagnostic and prognostic biomarker for CRC.

Intra-tumor heterogeneity of microRNA-92a, microRNA-375 and microRNA-424 in colorectal cancer

Various microRNAs (miRNAs) have been investigated in order to improve diagnostics and risk assessment in colorectal cancer (CRC). To clarify the potential of miRNA profiling in CRC, knowledge of intra-tumor heterogeneity in expression levels is crucial.The study aim was to estimate the intra-tumor variance of three selected miRNAs: miR-92a, miR-375 and miR-424 in CRC tissue. Material and methodsA retrospective study on archived formalin-fixed paraffin embedded tissue from 9 patients with CRC. miRNA tissue expression levels were analyzed by qRT-PCR on tissue representing luminal, central and invasive border zones. Variance components were estimated based on ∆∆Cp values using mixed modeling and presented as coefficients of variation (CV). ResultsIntra-tumor variance was approximately half of the variance observed between patients with a mean intra-tumor CV of 56.4% (range 33.1–77.1%) and a mean inter-patient CV of 101.7% (range 48.8–152.7%). Furthermore we found a significant systematic difference in expression levels between tumor zones for miR-92a and miR-375 with a luminal-invasive difference equal to 0.60 Cp (95% CI: 0.30–0.89, p=0.0003) for miR-92a and a luminal-invasive difference equal to 0.78 Cp (95% CI: 0.10–1.46, p=0.027) for miR-375. ConclusionWhile the intra-tumor variance of miR-92a, miR-375 and miR-424 is substantial, it only constitutes approximately 30% of the total variation. Functional deregulation between tumor zones might contribute to variations in measured expression levels, and thus knowledge of specific intra-tumor expression patterns is crucial in tissue sampling for research as well as in future diagnostics.

Synthesis and summary of patient‐reported outcome measures to inform the development of a core outcome set in colorectal cancer surgery

AimPatient‐reported outcome (PRO) measures (PROMs) are standard measures in the assessment of colorectal cancer (CRC) treatment, but the range and complexity of available PROMs may be hindering the synthesis of evidence. This systematic review aimed to: (i) summarize PROMs in studies of CRC surgery and (ii) categorize PRO content to inform the future development of an agreed minimum ‘core’ outcome set to be measured in all trials.MethodAll PROMs were identified from a systematic review of prospective CRC surgical studies. The type and frequency of PROMs in each study were summarized, and the number of items documented. All items were extracted and independently categorized by content by two researchers into ‘health domains’, and discrepancies were discussed with a patient and expert. Domain popularity and the distribution of items were summarized.ResultsFifty‐eight different PROMs were identified from the 104 included studies. There were 23 generic, four cancer‐specific, 11 disease‐specific and 16 symptom‐specific questionnaires, and three ad hoc measures. The most frequently used PROM was the EORTC QLQ‐C30 (50 studies), and most PROMs (n = 40, 69%) were used in only one study. Detailed examination of the 50 available measures identified 917 items, which were categorized into 51 domains. The domains comprising the most items were ‘anxiety’ (n = 85, 9.2%), ‘fatigue’ (n = 67, 7.3%) and ‘physical function’ (n = 63, 6.9%). No domains were included in all PROMs.ConclusionThere is major heterogeneity of PRO measurement and a wide variation in content assessed in the PROMs available for CRC. A core outcome set will improve PRO outcome measurement and reporting in CRC trials.