A New Biomarker of Fecal Bacteria for Non-Invasive Diagnosis of Colorectal Cancer
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Background The intestinal flora is correlated with the occurrence of colorectal cancer. We evaluate a new predictive model for the non-invasive diagnosis of colorectal cancer based on intestinal flora to verify the clinical application prospects of the intestinal flora as a new biomarker in non-invasive screening of colorectal cancer. Methods Subjects from two independent Asian cohorts (cohort I, consisting of 206 colorectal cancer and 112 healthy subjects; cohort II, consisting of 67 colorectal cancer and 54 healthy subjects) were included. A probe-based duplex quantitative PCR (qPCR) determination was established for the quantitative determination of candidate bacterial markers. Results We screened through the gutMEGA database to identify potential non-invasive biomarkers for colorectal cancer, including Prevotella copri ( Pc ), Gemella morbillorum ( Gm ), Parvimonas micra ( Pm ), Cetobacterium somerae ( Cs ), and Pasteurella stomatis ( Ps ). A predictive model with good sensitivity and specificity was established as a new diagnostic tool for colorectal cancer. Under the best cutoff value that maximizes the sum of sensitivity and specificity, Gm and Pm had better specificity and sensitivity than other target bacteria. The combined detection model of five kinds of bacteria showed better diagnostic ability than Gm or Pm alone (AUC = 0.861, P < 0.001). These findings were further confirmed in the independent cohort II. Particularly, the combination of bacterial markers and fecal immunochemical test (FIT) improved the diagnostic ability of the five bacteria (sensitivity 67.96%, specificity 89.29%) for patients with colorectal cancer. Conclusion Fecal-based colorectal cancer-related bacteria can be used as new non-invasive diagnostic biomarkers of colorectal cancer. Simultaneously, the molecular biomarkers in fecal samples are similar to FIT, have the applicability in combination with other detection methods, which is expected to improve the sensitivity of diagnosis for colorectal cancer, and have a promising prospect of clinical application.Hyperplastic Polyp
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Imaging biomarker
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Objective To investigate the expression and significance of δ-catenin in colorectal cancer(CRC),and explore the correlation between8-catenin expression and cell proliferation in colorectal cancer.Methods The expressions of 8-catenin and Ki-67 in 120 specimens of colorectal cancer were detected by immunohistochemistry in tissue microassay.The expression of 8-catenin was also determined in 30 paired colorectal cancer and normal colorectum by Western blot.Results Overexpression of 8-catenin was detected in 65.83%(79/120) of the 120 human colorectal cancer tissues,which was significantly higher than that in normal colorectum.The positive expression of 8-catenin was higher in advanced TNM stages(Ⅲ+ Ⅳ)of colorectal cancer(78.05%,32/41),compared to lower stages(Ⅰ+Ⅱ)(59.49%,47/79)(x~2=4.132,P= 0.042).The positive expression of 8-catenin was higher in poor differentiated colorectal cancer(82.14%,23/28),compared to well/moderate differentiated colorectal cancer(60.87%,56/92)(x~2=4-319,P = 0.038).The positive expression of 8-catenin was higher in colorectal cancer with lymph node metastasis(77.05%,47/61),compared to colorectal cancer without lymph node metastasis(54.24%,32/59)(x~2=6-939,P = 0.008).In addition,we also found that the overexpression of 8-catenin was positively correlated with proliferation of colorectal cancer which marked by Ki-67 staining in colorectal cancer(r=0.334,P 0.01).Conclusion 8-catenin overexpression might be involved in the initiation and progression of colorectal cancer.
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Objective To detect the expression and role of PTTG mRNA in human colorectal cancer.Methods The expression of PTTG mRNA was evaluated in 12 normal colorectal tissues,20 colorectal adenoma tissues and 44 colorectal cancer tissues by RT-PCR.Results The expression of PTTG mRNA in colorectal cancer was significantly higher than that in colorectal adenoma and normal colorectal tissues.The PTTG mRNA expression in the Dukes C,D colorectal cancer was higher than that in the Dukes A,B cancer(P0.05).The expression in the colorectal cancer with lymph node metastasis was higher than that in the cancer without lymph node metastasis(P0.05).Conclusion The expression of PTTG mRNA increases in colorectal cancer,and is related with cell differentiation and metastasis.The abnormal expression of PTTG probably participates in genesis and development of colorectal cancers.
Colorectal adenoma
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A pathophysiologic model of Alzheimer's disease (AD) has been recently proposed in which beta amyloid accumulation occurs earlier (indexed by abnormal CSF Abeta42), followed by tau-mediated neuronal injury and dysfunction (abnormal CSF tau or FDG-PET) and lastly atrophic changes (abnormal hippocampal volume, HV). The aim of this study is to validate this model by comparing clinical features and conversion to AD and other dementias among groups of patients with mild cognitive impairment (MCI) with different abnormal biomarker profiles. The patients of this study were 58 with MCI in whom AD biomarkers (CSF Abeta42 and tau, temporoparietal hypometabolism on 18F-FDG PET, and hippocampal volume) were collected. Patients were divided into 3 groups of no abnormal biomarker, AD biomarker pattern (including 3 subgroups of early = only abnormal Abeta42, intermediate = abnormal Abeta42 and FDG-PET or tau, and late = abnormal Abeta42, FDG-PET or tau, and HV), and any other biomarker combination. MCI patients with AD biomarker pattern had lower behavioral disturbances than patients with any other biomarker combination (P <.0005) and lower performance on verbal and nonverbal memory than the other two groups (P = .07 and P = .004, respectively). Within the 3 subgroups with AD biomarker pattern there was a significant trend to higher rate of conversion to dementia (p for trend = .006). Moreover, AD was the type of incident dementia in 100% of patients with an AD biomarker pattern, but 0% and 27% in converters with no abnormal biomarker and any other biomarker combination, respectively (P = .002). Clinical cases representative of the three groups were also described. The results of this study provide evidence in favor of the dynamic biomarker model and support the use of biomarkers for the diagnosis of MCI due to AD according to the new recently published research criteria.
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Abstract Background: Solute carrier family 25 member 24 (SLC25A24) is a member of the mitochondrial solute vector (MSC) protein superfamily. More and more evidence suggested that SLC family members play an extremely important role in cancers. However, the biological function of SLC25A24 in colorectal cancer has not been reported. Methods: TCGA, GEO, UALCAN, Sangebox3.0 and TIDE databases were used to analyze SLC25A24 in colorectal cancer. The expression of SLC25A24 in 83 pairs of colorectal cancer tissues was detected by immunohistochemistry. qRT-PCR, Western blotting and apoptosis assays were used to explore the biological function of SLC25A24 in colorectal cancer. Results: Through analysis of multiple databases, we found that SLC25A24 expression was higher in colorectal cancer than in adjacent normal tissues, and higher expression of SLC25A24 had a better prognosis. This was verified by clinical case analysis. In addition, based on multiple algorithms of immune infiltration, we found that SLC25A24 was significantly associated with immune infiltration in colorectal cancer. SLC25A24 was significantly associated with clinicopathological features in 83 patients with colorectal cancer. Importantly, SLC25A24 knockdown significantly promoted the apoptosis ability of colorectal cancer cells. In addition, we also found that lower expression of SLC25A24 was associated with poor prognosis and low immunotherapy sensitivity in patients with colorectal cancer. Therefore, SLC25A24 might be a biomarker for the treatment of colorectal cancer. Conclusion: In summary, we found that SLC25A24 was higher expression in colorectal cancer than in adjacent normal tissues, and higher expression of SLC25A24 had a better prognosis. Importantly, we found that SLC25A24 inhibited apoptosis of colorectal cancer cells. In addition, SLC25A24 was associated with immune infiltration of colorectal cancer. Patients with lower expression of SLC25A24 were more prone to immune escape, while patients with higher expression of SLC25A24 were more conducive to immunotherapy. These results suggested that SLC25A24 might be a potential therapeutic target for patients with colorectal cancer.
Infiltration (HVAC)
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Abstract Colorectal cancer is a crucial health-threatening problem. In recent years, the treatment of colorectal cancer has continued improved and update. But the prognosis of advanced colorectal cancer is still disappointing. Galecitn-9 is a member of the galectin family which has been verified to have multiple biological regulatory functions. Our team has been studying the clinical application of the galectin family in gastric and colorectal cancer. However, we do not yet unveil the correlation between Galecitn-9 and colorectal cancer. This study aimed to elucidate the expression of Galecitn-9 in colorectal cancer and the effect of Galecitn-9 on colorectal cancer proliferation, migration and invasion.
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Different CSF biomarker combinations can provide conflicting diagnostic information in Alzheimer′s disease (AD). This is often attributed to differences in sensitivity and specificity, at the cohort level, between CSF markers (Aβ42, t-Tau, p-Tau181, t-Tau/Aβ42, and p-Tau181/Aβ42). When these biomarkers are analyzed against the same gold standard independently, conflicting biomarker information can also result from biomarker substructures not obvious to investigators. Previous studies have not examined conflicting biomarker information at the individual level (e.g., a profile showing normal Aβ42 levels but abnormal t-Tau/Aβ42 ratio may be interprted as AD-like even though the normal Aβ42 level argues against amyloid pathology). The prevalence of these conflicts and ways to resolve them are unknown. We measured CSF AD biomarker levels in one consecutive series (n=431) from Emory University using the multiplex AlzBio3 assay and surveyed the concordance rates between CSF biomarkers at the individual level. We also compared these results with those from clinical testing through a comparable ELISA. To resolve the issue of differential sensitivity and biomarker substructure, we then analyzed CSF AD biomarker levels through two-step clustering to identify naturally existing subgroups of biomarker profiles. Finally, to determine if the cluster membership or the combination of independent biomarker information confers greater information on prognosis, we analyzed if either predicted longitudinal cognitive changes in the Alzheimer’s Disease Neuro-Imaging Initiative (ADNI, n=409). Conflicting CSF biomarker information was very common: 59% of the Emory subjects and 37% of ADNI subjects had at least one biomarker providing diagnostic information distinct from the other biomarkers. Clustering analysis revealed three groupings: one characterized by p-Tau181/Aβ42>0.131 and longitudinal cognitive decline in MCI, and two others (including one characterized by Aβ42>258.5pg/mL) associated with cognitive stability. Within each cluster, concordant or discordant biomarker findings did not further distinguish rates of longitudinal cognitive decline. Conflicting information from different CSF AD biomarkers was common. A data-driven strategy accounting for all biomarker combinations identified naturally existing groupings each characterized by similar biochemical and prognostic profiles.
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