Proteomics and liquid biopsy characterization of human EMT-related metastasis in colorectal cancer.

Tumor cells undergo epithelial-mesenchymal transition (EMT), however, there is a room of disagreement in role of EMT heterogeneity to colorectal cancer metastasis (mCRC) evolution. To uncover new EMT-related metastasis proteins and pathways, we addressed the EMT status in colorectal cancer liver metastasis patient-derived CTCs to identify proteins that promote their distant metastasis. And then, we performed a comparative proteomic analysis in matched pairs of primary tumor tissues, adjacent mucosa tissues and liver metastatic tissues. By integrative analysis we show that, unstable Epithelial/Mesenchymal (E/M)-type CTCs had the strongest liver metastases formation ability and the proportion of E/M-type CTCs correlated with distant metastases. Using an optimized proteomic workflow including data independent acquisition (DIA) and parallel reaction monitoring (PRM), we identified novel EMT-related protein cluster (GNG2, COL6A1, COL6A2, DCN, COL6A3, LAMB2, TNXB, CAVIN1) and well-described (ERBB2) core protein level changes in EMT-related metastasis progression, and the proteomic data indicate ERBB2, COL6A1 and CAVIN1 are promising EMT-related metastatic biomarker candidates. This study contributes to our understanding of the role that EMT plays in CRC metastasis and identifies heterogeneous EMT phenotypes as a key piece for tumor progression and prognosis. We further propose that therapies targeting this aggressive subset (E/M-type) of CTCs and related protein may be worthy of exploration as potential suppressors of metastatic evolution.

MTUS1 is a promising diagnostic and prognostic biomarker for colorectal cancer.

BACKGROUND: The morbidity and mortality of colorectal cancer (CRC) remain high, posing a serious threat to human life and health. The early diagnosis and prognostic evaluation of CRC are two major challenges in clinical practice. MTUS1 is considered a tumour suppressor and can play an important role in inhibiting cell proliferation, migration, and tumour growth. Moreover, the expression of MTUS1 is decreased in different human cancers, including CRC. However, the biological functions and molecular mechanisms of MTUS1 in CRC remain unclear. METHODS: In the present study, data from The Cancer Genome Atlas (TCGA) database were analysed using R statistical software (version 3.6.3.) to evaluate the expression of MTUS1 in tumour tissues and adjacent normal tissues using public databases such as the TIMER and Oncomine databases. Then, 38 clinical samples were collected, and qPCR was performed to verify MTUS1 expression. We also investigated the relationship between MTUS1 expression and clinicopathological characteristics and elucidated the diagnostic and prognostic value of MTUS1 in CRC. In addition, the correlation between MTUS1 expression and immune infiltration levels was identified using the TIMER and GEPIA databases. Furthermore, we constructed and analysed a PPI network and coexpression modules of MTUS1 to explore its molecular functions and mechanisms. RESULTS: CRC tissues exhibited lower levels of MTUS1 than normal tissues. The logistic regression analysis indicated that the expression of MTUS1 was associated with N stage, TNM stage, and neoplasm type. Moreover, CRC patients with low MTUS1 expression had poor overall survival (OS). Multivariate analysis revealed that the downregulation of MTUS1 was an independent prognostic factor and was correlated with poor OS in CRC patients. MTUS1 expression had good diagnostic value based on ROC analysis. Furthermore, we identified a group of potential MTUS1-interacting proteins and coexpressed genes. GO and KEGG enrichment analyses showed that MTUS1 was involved in multiple cancer-related signalling pathways. Moreover, the expression of MTUS1 was significantly related to the infiltration levels of multiple cells. Finally, MTUS1 expression was strongly correlated with various immune marker sets. CONCLUSIONS: Our results indicated that MTUS1 is a promising biomarker for predicting the diagnosis and prognosis of CRC patients. MTUS1 can also become a new molecular target for tumour immunotherapy.

A nomogram for preoperative prediction of lymphatic infiltration in colorectal cancer: A personalized approach to clinical decision making.

Lymphatic infiltration (LI) is a key factor affecting the treatment of patients with colorectal cancer (CRC). Thus, the aim of this study was to develop and validate a nomogram for individual preoperative prediction of LI in patients with CRC.We conducted a retrospective analysis of 664 patients who received their initial diagnosis of CRC at our center. Those patients were allocated to a training dataset (n = 468) and a validation dataset (n = 196). The least absolute shrinkage and selection operator regression model was used for data dimension reduction and feature selection. The nomogram was constructed from the training dataset and internally verified using the concordance index (C-index), calibration, area under the receiver operating characteristic curve and decision curve analysis (DCA).The enhancement computed tomography reported N1/N2 classification, preoperative tumor differentiation, elevated carcinoembryonic antigen, and carbohydrate antigen19-9 level were selected as variables for the prediction nomogram. Encouragingly, the nomogram showed favorable calibration with C-index 0.757 in the training cohort and 0.725 in validation cohort. The DCA signified that the nomogram was clinically useful. The Kaplan-Meier survival curve showed that patients with LI had a worse prognosis and could benefit from postoperative adjuvant chemotherapy.Use common clinicopathologic factors, a non-invasive scale for individualized preoperative forecasting of LI was established conveniently. LI prediction has great significance for risk stratification of prognosis and treatment of resectable CRC.

Hematological parameters in high altitude residents: Tibetan natives versus Han migrants.

OBJECTIVE: Aim of our study was to compare hematological parameters in Tibetan natives with those in Han migrants living on the Tibet plateau in order to determine the potential effects of age, gender, and ethnicity on hematological response to hypoxia. METHODS: Blood hemoglobin (Hb, g/dl), hematocrit (Hct, %), red blood cells (RBC,10(6)/mm3) were measured in 3 588 healthy Tibetan natives and 3 371 Han migrants ranging in age from 5 to 72 years, living at a mean altitudes of 2 664 m, 3 813 m, 4 525m and 5 226 m. RESULTS: Hemoglobin (Hb) concentration analysis was made by multiple regression equations relating hemoglobin to altitude and age. For 2 093 Han males, Hb = 9.612+ 0.001440xaltitude+ 0.06148xage. For 1 948 Tibetan males, Hb =12.202+ 0.000462xaltitude+ 0.02893xage. For 1 278 Han females, Hb = 10.858+ 0.000939xaltitude+ 0.02632xage. For 1 640 Tibetan females, Hb = 11.402+ 0.000626xaltitude+ 0.00412xage. Each of the four equations was statistically significant (P < 0.001), and had variance (r2) of 0.86 or more, indicating that altitude and age accounted for at least 85% of the variation in hemoglobin levels. The coefficients for altitude and for age were higher (P < 0.05) in Han males than in Tibetan males and higher (P < 0.05) in Han females than in Tibetan females. The Tibetan postmenopausal females had higher Hb values than premenopausal females only presented at altitude above 4 000 m while this phenomenon was beginning at altitude of 2 664 m among Han females. CONCLUSION: We conclude that gender and increasing age in Tibetans are associated with lower hemoglobin values than those in Han at high altitude, and we speculate that genetic factors seems to be important.

Antioxidant supplementation for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a meta-analysis of randomized controlled trials.

BACKGROUND: Acute pancreatitis remains the most common major complication of endoscopic retrograde cholangiopancreatography (ERCP). The pathogenesis of post-ERCP acute pancreatitis may be mediated by oxygen-derived free radicals, which could be ameliorated by antioxidants. Antioxidant supplementation may potentially prevent post-ERCP pancreatitis. We performed a meta-analysis of randomized controlled trials to evaluate the effect of prophylactic antioxidant supplementation compared with control on the prevention of post-ERCP pancreatitis. METHODS: PubMed and Embase databases were searched to identify relevant trials. A standardized Excel file was used to extract data by two independent authors. Results were expressed as risk ratio (RR) with accompanying 95% confidence interval (CI). The meta-analysis was performed with the fixed-effects model or random-effects model according to heterogeneity. RESULTS: Eleven studies involving 3,010 patients met our inclusion criteria. Antioxidant supplementation did not significantly decrease the incidence of post-ERCP pancreatitis (RR, 0.92; 95% CI, 0.65-1.32; P = 0.665). There was also no statistical difference in the severity grades between the antioxidant group and control group. CONCLUSIONS: Based on current evidence, antioxidant supplementation shows no beneficial effect on the incidence and the severity of post-ERCP pancreatitis; thus, there is currently a lack of evidence to support using antioxidants for the prevention of post-ERCP pancreatitis.

Meta-analysis of randomized controlled trials on the efficacy of thoracic epidural anesthesia in preventing atrial fibrillation after coronary artery bypass grafting.

BACKGROUND: Postoperative atrial fibrillation (POAF) is one of the most common complications in patients undergoing coronary artery bypass grafting (CABG). The goal of this meta-analysis was to evaluate the efficacy of thoracic epidural anesthesia (TEA) in preventing POAF in adult patients undergoing CABG. METHODS: MEDLINE and EMBASE were searched to identify randomized controlled trails in adult patients undergoing CABG who were randomly assigned to receive general anesthesia plus thoracic epidural anesthesia (GA + TEA) or general anesthesia only (GA). Two authors independently extracted data using a standardized Excel file. The primary outcome measure was the incidence of POAF. We used DerSimonian-Laird random-effects models to compute summary risk ratios with 95% confidence intervals. RESULTS: Five studies involving 540 patients met our inclusion criteria. No significant difference in the incidence of POAF was observed between the two groups (risk ratio, 0.61; 95% confidence interval, 0.33 to 1.12; P = 0.11), with significant heterogeneity among the studies (I2 = 73%, P = 0.005). Sensitivity analyses by primary endpoint, methodological quality and surgical technique yielded similar results. CONCLUSIONS: The limited evidence suggests that TEA shows no beneficial efficacy in preventing POAF in adult patients undergoing CABG. However, the results of this meta-analysis should be interpreted with caution due to significant heterogeneity of the studies included. Thus, the potential infuence of TEA on the incidence of atrial fibrillation following CABG warrants further investigation.

Lack of efficacy of probiotics in preventing ventilator-associated pneumonia probiotics for ventilator-associated pneumonia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Ventilator-associated pneumonia (VAP) remains a common hazardous complication in patients who are mechanically ventilated and is associated with increased morbidity and mortality.We undertook a systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy and safety of probiotics for the prevention of VAP. METHODS: The PubMed and EMBASE databases were searched to identify randomized controlled trials comparing probiotics with control for VAP in adult patients undergoing mechanical ventilation.The primary outcome was the incidence of VAP. Secondary outcomes included ICU mortality,hospital mortality, urinary tract infection, catheter-related bloodstream infection, diarrhea, length of ICU stay, length of hospital stay, and duration of mechanical ventilation. RESULTS: A total of 1,142 patients from seven trials were subjected to meta-analysis. Probiotics did not significantly decrease the incidence of VAP (OR, 0.82; 95% CI, 0.55-1.24; P 5 .35), with low heterogeneity among the studies ( I 2 5 36.5%, P 5 .15). Probiotics also did not appear to significantly alter any of the other meta-analysis end points. CONCLUSIONS: The limited evidence suggests that probiotics show no beneficial effect in patients who are mechanically ventilated; thus, probiotics should not be recommended for routine clinical application. However, the results of this meta-analysis should be interpreted with caution because of the heterogeneity among study designs. Future studies should focus on the safety of probiotics.

[Effects of transforming growth factor-beta1 on rat cardiocyte hypertrophy].

AIM: To investigate the effects of transforming growth factor-beta1 (TGF-beta1) and signal protein Smad3 on rat myocardial hypertrophy. METHODS: The total protein was analysed by flow cytometer assay to judge the hypertrophy of myocardial cell incubated with different level of TGF-beta1 in cultured myocardial cells of neonatal rats. The models of rat cardiac hypertrophy were produced with constriction of the abdominal aorta. At the different time after the operation, the rats were killed, and the left ventricular mass indexes (LVMl) were investigated. The mRNA expressions of TGF-beta1 and Smad3 of cultured cells and hypertrophic left ventricles were assessed by RT-PCR, the protein expressions of Smad3 were assessed by Western blot. RESULTS: In cultured neonatal myocardial cells, different level TGF-beta1 could significantly increase the total protein, and TGF-beta1 (3 ng/ml) could increase the expression of mRNA and protein of Smad3 and continued for 8 h of cultured cardiomyocytes. The LVMI and the expression of TGF-beta1 mRNA and Smad3 mRNA/protein of hypertrophic left ventricle were increased at the 3rd day after the operation and continued for 4 weeks. The peak expression of them was in 2 weeks after operation. CONCLUSION: TGF-beta1 has the effects on rat myocardial hypertrophy, signal protein Smad3 is included in the pathologic progress of rat myocardial hypertrophy.