Colorectal cancer is currently the third most common malignancy in the world. Patients have excellent prognosis following surgical resection if their tumour is still localized at diagnosis. By contrast, once the tumour has started to metastasize, prognosis is much poorer. Accurate early detection can therefore significantly reduce the mortality from this disease. However, current tests either lack the required sensitivity and selectivity or are costly and invasive. Improved biomarkers, or panels of biomarkers, are therefore urgently required. We have addressed current screening strategies and potential protein biomarkers that have been proposed. The role of both discovery and hypothesis-driven proteomics approaches for biomarker discovery and validation is discussed. Using such approaches we show how multiple reaction monitoring (MRM) can be successfully developed and used for quantitative multiplexed analysis of potential faecal biomarkers.

BACKGROUND:The onset of the term human parturition involves myometrial gene expression changes to transform the uterus from a quiescent to a contractile phenotype. It is uncertain whether the same changes occur in the uterus during preterm labor. OBJECTIVE: This study aimed to compare the myometrial gene expression between term and preterm labor and to determine whether the presence of acute clinical chorioamnionitis or twin gestation affects these signatures. STUDY DESIGN: Myometrial specimens were collected during cesarean delivery from the following 7 different groups of patients: term not in labor (n¼31), term labor (n¼13), preterm not in labor (n¼21), preterm labor with acute clinical chorioamnionitis (n¼6), preterm labor with no acute clinical chorioamnionitis (n¼9), twin preterm not in labor (n¼8), and twin preterm labor with no acute clinical chorioamnionitis (n¼5). RNA was extracted, reverse transcribed and quantitative polymerase chain reactions were performed on 44 candidate genes (with evidence for differential expression in human term labor) using the Fluidigm platform. Computational analysis was performed using 2-class unpaired Wilcoxon tests and principal component analysis.RESULTS: Computational analysis revealed that gene expression in the preterm myometrium, irrespective of whether in labor or not in labor, clustered tightly and is clearly different from the term labor and term notin-labor groups. This was true for both singleton and twin pregnancies. Principal component analysis showed that 57% of the variation was explained by 3 principal components. These 44 genes interact in themes of prostaglandin activity and inflammatory signaling known to be important during term labor, but are not a full representation of the myometrium transcriptional activity. CONCLUSION: The myometrial contractions associated with preterm labor are associated with a pattern of gene expression that is distinct from term labor. Therefore, preterm labor may be initiated by a different myometrial process or processes outside the myometrium.

Background Preterm birth (PTB) is the leading cause of death in children under five years. Spontaneous preterm birth (SPTB) is the major cause of preterm delivery. The key risk factors for SPTB are women who have a short cervix and women who have had previous preterm birth. Cervical cerclage has been used for several decades and has shown to decrease rates of preterm birth. The most commonly used cerclage techniques were described by Shirodkar and McDonald, with no current consensus on the preferred technique. The objective of this review is to determine and compare the effectiveness of both techniques. Methods Studies will be sourced from six electronic databases, as well as from experts in the field, reference lists, and grey literature. Eligible studies will include pregnant women, with a singleton or twin pregnancy, requiring a cervical cerclage, using either the Shirodkar or McDonald technique and run comparative analyses between the two techniques. Randomized control trials (RCT)s, non-randomized control trials, and cohort studies will be eligible. Two independent reviewers will conduct study screening at abstract and full-text level, data extraction and risk of bias assessment. Discrepancies will be resolved by a consensus third reviewer if required. Fixed-effects or random-effects models will be used where appropriate to synthesize results. Alternative synthesis methods will be investigated in instances where a meta-analysis is not appropriate, such as summarizing effect estimates, combining P values, vote counting based on direction of effect, or synthesis in narrative form. Discussion This review will synthesize the evidence on both the Shirodkar and McDonald cerclage method, and will help clinicians and health services to determine and deliver best practice antenatal care that has the potential to make an impact on preterm birth. Systematic review registration PROSPERO on 25 of May, 2020 with registration number CRD42020177386