Integrated metagenomic and metabolomic analysis reveals distinct gut-microbiome-derived phenotypes in early-onset colorectal cancer.

OBJECTIVE: The incidence of early-onset colorectal cancer (EO-CRC) is steadily increasing. Here, we aimed to characterise the interactions between gut microbiome, metabolites and microbial enzymes in EO-CRC patients and evaluate their potential as non-invasive biomarkers for EO-CRC. DESIGN: We performed metagenomic and metabolomic analyses, identified multiomics markers and constructed CRC classifiers for the discovery cohort with 130 late-onset CRC (LO-CRC), 114 EO-CRC subjects and age-matched healthy controls (97 LO-Control and 100 EO-Control). An independent cohort of 38 LO-CRC, 24 EO-CRC, 22 LO-Controls and 24 EO-Controls was analysed to validate the results. RESULTS: Compared with controls, reduced alpha-diversity was apparent in both, LO-CRC and EO-CRC subjects. Although common variations existed, integrative analyses identified distinct microbiome-metabolome associations in LO-CRC and EO-CRC. Fusobacterium nucleatum enrichment and short-chain fatty acid depletion, including reduced microbial GABA biosynthesis and a shift in acetate/acetaldehyde metabolism towards acetyl-CoA production characterises LO-CRC. In comparison, multiomics signatures of EO-CRC tended to be associated with enriched Flavonifractor plauti and increased tryptophan, bile acid and choline metabolism. Notably, elevated red meat intake-related species, choline metabolites and KEGG orthology (KO) pldB and cbh gene axis may be potential tumour stimulators in EO-CRC. The predictive model based on metagenomic, metabolomic and KO gene markers achieved a powerful classification performance for distinguishing EO-CRC from controls. CONCLUSION: Our large-sample multiomics data suggest that altered microbiome-metabolome interplay helps explain the pathogenesis of EO-CRC and LO-CRC. The potential of microbiome-derived biomarkers as promising non-invasive tools could be used for the accurate detection and distinction of individuals with EO-CRC.

Function and mechanism of MCM8 in the development and progression of colorectal cancer.

Colorectal cancer (CRC) has become a global health problem which has almost highest morbidity and mortality in all types of cancers. This study aimed to uncover the biological functions and underlying mechanism of MCM8 in the development and progression of CRC. The expression level of MCM8 was found to be upregulated in CRC tissues and significantly associated with tumor grade and patients' survival. Knocking down MCM8 expression in CRC cells could restrain cell growth and cell motility while promoting cell apoptosis in vitro, as well as inhibit tumor growth in xenograft mice model. Based on the RNA screening performing on CRC cells with or without MCM8 knockdown and the following IPA analysis, CHSY1 was identified as a potential target of MCM8 in CRC, whose expression was also found to be higher in tumor tissues than in normal tissues. Moreover, it was demonstrated that MCM8 may regulate the expression of CHSY1 through affecting its NEDD4-mediated ubiquitination, both of which synergistically execute tumor promotion effects on CRC. In conclusion, the outcomes of our study showed the first evidence that MCM8 act as a tumor promotor in CRC, and may be a promising therapeutic target of CRC treatment.

A clinical-radiomics nomogram for the preoperative prediction of lung metastasis in colorectal cancer patients with indeterminate pulmonary nodules.

OBJECTIVES: To develop and validate a clinical-radiomics nomogram for preoperative prediction of lung metastasis for colorectal cancer (CRC) patients with indeterminate pulmonary nodules (IPN). METHODS: 194 CRC patients with lung nodules were enrolled in this study (136 in the training cohort and 58 in the validation cohort). To evaluate the probability of lung metastasis, we developed three models, the clinical model with significant clinical risk factors, the radiomics model with radiomics features constructed by the least absolute shrinkage and selection operator algorithm, and the clinical-radiomics model with significant variables selected by the stepwise logistic regression. The Akaike information criterion (AIC) was used to compare the relative strength of different models, and the area under the curve (AUC) was used to quantify the predictive accuracy. The nomogram was developed based on the most appropriate model. Decision-curve analysis was applied to assess the clinical usefulness. RESULTS: The clinical-radiomics model (AIC = 98.893) with the lowest AIC value compared with that of the clinical-only model (AIC = 138.502) or the radiomics-only model (AIC = 116.146) was identified as the best model. The clinical-radiomics nomogram was also successfully developed with favourable discrimination in both training cohort (AUC = 0.929, 95% CI: 0.885-0.974) and validation cohort (AUC = 0.922, 95% CI: 0.857-0.986), and good calibration. Decision-curve analysis confirmed the clinical utility of the clinical-radiomics nomogram. CONCLUSIONS: In CRC patients with IPNs, the clinical-radiomics nomogram created by the radiomics signature and clinical risk factors exhibited favourable discriminatory ability and accuracy for a metastasis prediction. KEY POINTS: • Clinical features can predict lung metastasis of colorectal cancer patients. • Radiomics analysis outperformed clinical features in assessing the risk of pulmonary metastasis. • A clinical-radiomics nomogram can help clinicians predict lung metastasis in colorectal cancer patients.

The preoperative SUVmax for (18)F-FDG uptake predicts survival in patients with colorectal cancer.

BACKGROUND: The study was to investigate whether (18)F-fluorodeoxyglucose ((18)F-FDG) uptake, analyzed by positron emission tomography (PET), can be used preoperatively to predict survival in Chinese patients with colorectal carcinoma. METHODS: A prospectively maintained colorectal cancer database was retrospectively reviewed between June 2009 and December 2011. All included patients had been newly diagnosed with colorectal cancer (of various stages) and evaluated by (18)F-FDG-PET/computed tomography (CT) within the 2 weeks preceding surgery. Univariate and multivariate analyses were used to determine whether the maximal standardized uptake value (SUVmax) and various clinicopathological and immunohistochemical factors were correlated with survival. Receiver operating characteristics (ROC) curve and Kaplan-Meier survival curve analyses were used to explore whether SUVmax could predict survival in these patients. RESULTS: A total of 107 patients were enrolled in the study (mean age, 59.26 ± 12.66 years; 66.35% males), with 77 surviving to the end of follow-up (average 60 months). Univariate analysis indicated that tumor size, TNM stage, nodal metastasis, the ratio of metastasized nodes to retrieved nodes, cyclin D1 immunostaining and SUVmax correlated with survival (P < 0.05). Multivariate analysis showed that only TNM stage and SUVmax were associated with survival (P < 0.05). ROC curve analysis determined the optimal SUVmax cutoff for predicting survival to be 11.85 (sensitivity, 73.3%; specificity, 75.3%). Survival was significantly longer in patients with preoperative SUVmax ≤ 11.85 (P < 0.001, log-rank test). CONCLUSIONS: SUVmax, measured by (18)F-FDG-PET/CT, provides a useful preoperative prognostic factor for patients with colorectal cancer.

Unfavorable effect of small tumor size on cause-specific survival in stage IIA colon cancer, a SEER-based study.

BACKGROUND: We sought to determine the prognostic role of tumor size on cause-specific survival (CSS) of patients with stage IIA colon cancer. METHODS: Surveillance, Epidemiology and End Results (SEER) database was utilized to identify patients with stage IIA colorectal cancer (examined lymph nodes ≥12) diagnosed from 1988 to 2003. The prognostic effect of tumor size on CSS was evaluated by univariate and multivariate analyses. RESULTS: A total of 8775 patients were enrolled in the analysis. The median follow-up time was 109 months. As determined by minimal P value method, tumor sizes of 2.5 and 6.0 cm were used as optimal cutoff value to divide the cohort. The 8-year CSS of colon cancer with tumor sizes ≤2.5, 2.6-6.0, and >6.0 cm was 81.6, 86.2, and 86.7% respectively (P = 0.003). In the multivariate analysis of colon cancer, using ≤2.5-cm tumors as reference, decreased hazard ratio (HR) of CSS was observed in 2.6-6.0 cm (HR, 0.736; 95% confidence interval (CI), 0.599-0.905; P = 0.004) and >6.0 cm (HR, 0.770; 95% CI, 0.619-0.958; P = 0.019) tumors. CONCLUSIONS: In stage IIA colon cancer, small tumor size represented a subset with decreased CSS. Further studies are merited to validate the unfavorable prognostic role of small tumor size in stage IIA colon cancer.

TPX2 is a novel prognostic marker for the growth and metastasis of colon cancer.

BACKGROUND: We have previously demonstrated an aberrant overexpression of the microtubule-associated protein TPX2 in colon cancer using a genome-wide gene expression profiling analysis. Here, we aim to investigate its expression pattern, clinical significance, and biological function in colon cancer. METHODS: TPX2 expression was analyzed in human colon cancer cell lines and tumor samples. The effect of TPX2 on cell proliferation, tumorigenesis, and metastasis was examined in vitro and in vivo. RESULTS: TPX2 was overexpressed in 129 of the 203 (60.8%) colon cancer metastatic lesions, with the expression being significantly higher than that in primary cancerous tissue and normal colon mucosa. Overexpression of TPX2 was significantly associated with clinical staging, vessel invasion, and metastasis. In survival analyses, patients with TPX2 overexpression had worse overall survival and metastasis free survival, suggesting that deregulation of TPX2 may contribute to the metastasis of colon cancer. Consistent with this, suppression of TPX2 expression inhibited proliferation and tumorigenicity of colon cancer cells both in vitro and in vivo. Strikingly, we found that TPX2 knockdown significantly attenuated the migration and invasion ability of colon cancer cells, which was further shown to be mechanistically associated with AKT-mediated MMP2 activity. CONCLUSIONS: These findings suggest that TPX2 plays an important role in promoting tumorigenesis and metastasis of human colon cancer, and may represent a novel prognostic biomarker and therapeutic target for the disease.

Multi-center evaluation of machine learning-based radiomic model in predicting disease free survival and adjuvant chemotherapy benefit in stage II colorectal cancer patients.

BACKGROUND: Our study aimed to explore the potential of radiomics features derived from CT images in predicting the prognosis and response to adjuvant chemotherapy (ACT) in patients with Stage II colorectal cancer (CRC). METHODS: A total of 478 patients with confirmed stage II CRC, with 313 from Shanghai (Training set) and 165 from Beijing (Validation set) were enrolled. Optimized features were selected using GridSearchCV and Iterative Feature Elimination (IFE) algorithm. Subsequently, we developed an ensemble random forest classifier to predict the probability of disease relapse.We evaluated the performance of the model using the concordance index (C-index), precision-recall curves, and area under the precision-recall curves (AUCPR). RESULTS: A radiomic model (namely the RF5 model) consisting of four radiomics features and T stage were developed. The RF5 model performed better than simple radiomics features or T stage alone, with higher C-index and AUCPR, as well as better sensitivity and specificity (C-indexRF5: 0.836; AUCPR = 0.711; Sensitivity = 0.610; Specificity = 0.935). We identified an optimal cutoff value of 0.1215 to split patients into high- or low-score subgroups, with those in the low-score group having better disease-free survival (DFS) (Training Set: P = 1.4e-11; Validation Set: P = 0.015). Furthermore, patients in the high-score group who received ACT had better DFS compared to those who did not receive ACT (P = 0.04). However, no statistical difference was found in low-score patients (P = 0.17). CONCLUSION: The radiomic model can serve as a reliable tool for assessing prognosis and identifying the optimal candidates for ACT in Stage II CRC patients. TRIAL REGISTRATION: Retrospectively registered.

BST2 induced macrophage M2 polarization to promote the progression of colorectal cancer.

Background: Tumor-associated macrophages (TAMs) are one of the most prominent tumor-infiltrating immune cells in the tumor microenvironment (TME) of CRC and play a vital role in the progression of CRC. BST2 was predicted to be associated with the infiltration of TAMs. However, its potential function by which CRC cells and TAMs interact with each other still needs further investigation. Methods: The target genes in CRC were selected by bioinformatics screening. The level of bone marrow stromal cell antigen 2 (BST2) in CRC cells and tissues was determined by qRT‒PCR, Western blotting, and immunohistochemistry staining. In vitro and in vivo assays were applied to clarify the function of BST2. Results: In this study, according to bioinformatics analysis, a nomogram based on the risk score (constructed by BST2 and CAV1 (caveolin-1)) and clinical features was built and displayed satisfactory prognostic value. Upregulated BST2 was significantly related to Braf mutation, dMMR/MSI-H, CMS1 subtype, and immune response and was a potential biomarker for predicting immune checkpoint blockade therapy. Silencing BST2 in CRC obviously restrained CRC progression and M2 TAM polarization. The infiltration of TAMs was positively correlated with the high expression of BST2, and depletion of TAMs alleviated the protumoural effect of BST2 in CRC in vivo. In vitro experiments revealed that a reduction in BST2 in CRC inhibited CRC proliferation and migration and also M2 polarization. Conclusion: These findings indicated that BST2 played a vital role in CRC progression and might be a predictable marker for immunotherapy.

CNN2 silencing inhibits colorectal cancer development through promoting ubiquitination of EGR1.

Colorectal cancer (CRC) is one of the most commonly diagnosed malignant tumors of the digestive tract. H2-calponin (CNN2), an actin cytoskeleton-binding protein, is an isoform of the calponin protein family whose role in CRC is still unknown. Research based on clinical samples showed the up-regulation of CNN2 in CRC and its association with tumor development, metastasis, and poor prognosis of patients. Both in vitro loss-of-function and gain-of-function experiments showed that CNN2 participates in CRC development through influencing malignant cell phenotypes. In vivo, xenografts formed by CNN2 knockdown cells also showed a slower growth rate and smaller final tumors. Furthermore, EGR1 was identified as a downstream of CNN2, forming a complex with CNN2 and YAP1 and playing an essential role in the CNN2-induced regulation of CRC development. Mechanistically, CNN2 knockdown down-regulated EGR1 expression through enhancing its ubiquitination, thus decreasing its protein stability in a YAP1-dependent manner. In summary, CNN2 plays an EGR1-dependent promotion role in the development and progression of CRC, which may be a promising therapeutic target for CRC treatment.

KIF15 knockdown inhibits colorectal cancer proliferation and migration through affecting the ubiquitination modification of NRAS.

As one of the most common malignancies, colorectal cancer (CRC) requires a thorough understanding of the mechanisms that promote its development and the discovery of new therapeutic targets. In this study, immunohistochemical staining confirmed significantly higher expression levels of KIF15 in CRC. qPCR and western blot results demonstrated the effective suppression of KIF15 mRNA and protein expression by shKIF15. Downregulation of KIF15 inhibited the proliferation and migration of CRC cells while promoting apoptosis. In addition, evidence from the xenograft experiments in nude mice demonstrated that KIF15 knockdown also suppressed tumor growth. Through bioinformatics analysis, the downstream molecular NRAS and Rac signaling pathway associated with KIF15 were identified. KIF15 knockdown was found to inhibit NRAS expression and disrupt Rac signaling pathway. Moreover, WB and Co-IP assays revealed that KIF15 reduced the ubiquitination modification of NRAS protein by interacting with the E3 ligase MDM2, thereby enhancing NRAS protein stability. Functionally, NRAS knockdown was shown to inhibit cell proliferation and migration. In conclusion, KIF15 promoted CRC progression by regulating NRAS expression and Rac signaling pathway.

LncRNA CACClnc promotes chemoresistance of colorectal cancer by modulating alternative splicing of RAD51.

Long non-coding RNAs (lncRNAs) play important roles in carcinogenesis. However, the effect of lncRNA on chemoresistance and RNA alternative splicing remains largely unknown. In this study, we identified a novel lncRNA, CACClnc, which was upregulated and associated with chemoresistance and poor prognosis in colorectal cancer (CRC). CACClnc promoted CRC resistance to chemotherapy via promoting DNA repair and enhancing homologous recombination in vitro and in vivo. Mechanistically, CACClnc specifically bound to Y-box binding protein 1 (YB1, a splicing factor) and U2AF65 (a subunit of U2AF splicing factor), promoting the interaction between YB1 and U2AF65, and then modulated alternative splicing (AS) of RAD51 mRNA, and consequently altered CRC cell biology. In addition, expression of exosomal CACClnc in peripheral plasma of CRC patients can effectively predict the chemotherapy effect of patients before treatment. Thus, measuring and targeting CACClnc and its associated pathway could yield valuable insight into clinical management and might ameliorate CRC patients' outcomes.

Dysbiosis of human gut microbiome in young-onset colorectal cancer.

The incidence of sporadic young-onset colorectal cancer (yCRC) is increasing. A significant knowledge gap exists in the gut microbiota and its diagnostic value for yCRC patients. Through 16S rRNA gene sequencing, 728 samples are collected to identify microbial markers, and an independent cohort of 310 samples is used to validate the results. Furthermore, species-level and functional analysis are performed by metagenome sequencing using 200 samples. Gut microbial diversity is increased in yCRC. Flavonifractor plautii is an important bacterial species in yCRC, while genus Streptococcus contains the key phylotype in the old-onset colorectal cancer. Functional analysis reveals that yCRC has unique characteristics of bacterial metabolism characterized by the dominance of DNA binding and RNA-dependent DNA biosynthetic process. The random forest classifier model achieves a powerful classification potential. This study highlights the potential of the gut microbiota biomarkers as a promising non-invasive tool for the accurate detection and distinction of individuals with yCRC.

LncRNA MIR17HG promotes colorectal cancer liver metastasis by mediating a glycolysis-associated positive feedback circuit.

Glycolysis plays a crucial role in reprogramming the metastatic tumor microenvironment. A series of lncRNAs have been identified to function as oncogenic molecules by regulating glycolysis. However, the roles of glycolysis-related lncRNAs in regulating colorectal cancer liver metastasis (CRLM) remain poorly understood. In the present study, the expression of the glycolysis-related lncRNA MIR17HG gradually increased from adjacent normal to CRC to the paired liver metastatic tissues, and high MIR17HG expression predicted poor survival, especially in patients with liver metastasis. Functionally, MIR17HG promoted glycolysis in CRC cells and enhanced their invasion and liver metastasis in vitro and in vivo. Mechanistically, MIR17HG functioned as a ceRNA to regulate HK1 expression by sponging miR-138-5p, resulting in glycolysis in CRC cells and leading to their invasion and liver metastasis. More interestingly, lactate accumulated via glycolysis activated the p38/Elk-1 signaling pathway to promote the transcriptional expression of MIR17HG in CRC cells, forming a positive feedback loop, which eventually resulted in persistent glycolysis and the invasion and liver metastasis of CRC cells. In conclusion, the present study indicates that the lactate-responsive lncRNA MIR17HG, acting as a ceRNA, promotes CRLM through a glycolysis-mediated positive feedback circuit and might be a novel biomarker and therapeutic target for CRLM.

CT Morphological Features Integrated With Whole-Lesion Histogram Parameters to Predict Lung Metastasis for Colorectal Cancer Patients With Pulmonary Nodules.

Purpose: To retrospectively identify the relationships between both CT morphological features and histogram parameters with pulmonary metastasis in patients with colorectal cancer (CRC) and compare the efficacy of single-slice and whole-lesion histogram analysis. Methods: Our study enrolled 196 CRC patients with pulmonary nodules (136 in the training dataset and 60 in the validation dataset). Twenty morphological features of contrast-enhanced chest CT were evaluated. The regions of interests were delineated in single-slice and whole-tumor lesions, and 22 histogram parameters were extracted. Stepwise logistic regression analyses were applied to choose the independent factors of lung metastasis in the morphological features model, the single-slice histogram model and whole-lesion histogram model. The areas under the curve (AUC) was applied to quantify the predictive accuracy of each model. Finally, we built a morphological-histogram nomogram for pulmonary metastasis prediction. Results: The whole-lesion histogram analysis (AUC of 0.888 and 0.865 in the training and validation datasets, respectively) outperformed the single-slice histogram analysis (AUC of 0.872 and 0.819 in the training and validation datasets, respectively) and the CT morphological features model (AUC of 0.869 and 0.845 in the training and validation datasets, respectively). The morphological-histogram model, developed with significant morphological features and whole-lesion histogram parameters, achieved favorable discrimination in both the training dataset (AUC = 0.919) and validation dataset (AUC = 0.895), and good calibration. Conclusions: CT morphological features in combination with whole-lesion histogram parameters can be used to prognosticate pulmonary metastasis for patients with colorectal cancer.

[Short to midterm results of endovascular for 105 case of infrarenal abdominal aortic aneurysms].

OBJECTIVE: To assess short to midterm outcome of endovascular aneurysm repair (EVAR) of infrarenal abdominal aortic aneurysms (AAA) in 105 cases. METHODS: Stent-grafts were placed into 105 patients with infrarenal AAA between January 2001 and February 2007. The clinical data of those cases were retrospectively analyzed. RESULTS: Primary technical success rate was 100%. Eighty-two cases (78.09%) were followed-up for 1 to 73 months (mean, 8.9 +/- 5.8 months). Three cases (2.86%) died during peri-operative period, from acute cardiac infarction, multi-organ failure and significant upper gastrointestinal bleeding, respectively. Another one died from hepatic cancer 30 months after EVAR. Twenty-one cases experienced primary endoleak. Eighteen were type I, among which 10 underwent secondary intervention in the form of balloon dilatation (n = 9) and stent-graft placement (n = 1), 8 sealed spontaneously. Two cases were type II and sealed spontaneously. One type III was treated by placing a stent-graft. An emergent femorofemoral crossover was performed for one graft limb thrombosis 2 weeks after EVAR. Four late type I endoleaks occurred. One stent-graft migration without endoleak was cured conservatively. Two stent-graft infections occurred 1 month and 3 months after EVAR respectively, and were cured with debridement, drainage and antibiotics. Nine femorofemoral or iliofemoral bypass and three internal iliac bypasses were all patent during the follow-up period. CONCLUSION: Endovascular repair is a safe and effective method for infrarenal AAA with perfect short to midterm outcomes.

A long non-coding RNA signature for predicting survival in patients with colorectal cancer.

Dysregulation of long non-coding RNA (lncRNA) plays important roles in cancer development and progression. In this work, we attempted to develop a lncRNA signature to improve prognosis prediction of colorectal cancer. A comprehensive analysis for the lncRNA expression and corresponding clinical information of 344 colorectal patients has been performed based on the data from The Cancer Genome Atlas (TCGA). We randomly divided TCGA data into a training set (n = 172) and a testing set (n = 172). A four-lncRNA signature has been established which was significantly associated with the overall survival of colorectal cancer patients. Based on the four-lncRNA signature, the training set can be classified into high-risk and low-risk groups with significantly different survival. The result can be further validated in the testing dataset and another independent dataset. Further analyses suggested that the prognostic power of the four-lncRNA signature was independent of other clinical variables. The identification of lncRNA signature indicated that lncRNAs could be novel independent biomarkers for predicting the survival in patients with colorectal cancer.

Poorer prognosis in young female patients with non-metastatic colorectal cancer: a hospital-based analysis of 5,047 patients in China.

PURPOSE: To investigate the association of age and sex on survival in non-metastatic colorectal cancer (CRC) patients and to identify groups at high risk for poor outcomes. MATERIALS AND METHODS: We performed a retrospective analysis of 5,047 non-metastatic CRC patients from 2008 to 2013. Data regarding age at diagnosis; gender; tumor site; tumor stage; differentiation; lymphatic, neural or vascular invasion; and survival outcomes were collected. Patients were stratified into 10-year age groups (≤35, 36-45, 46-55, 56-65, 66-75, >75) and then further analyzed in three age groups (≤35, 36-75, >75). Disease-free survival (DFS) and overall survival (OS) were evaluated using univariate and multivariate Cox regression models. RESULTS: Of the 5,047 eligible patients, 41.3% were female. The tumor stages were balanced between the genders. In the female patients, the tumor stages were similarly distributed among the different age groups, while younger male patients were diagnosed with more advanced disease (P<0.001 for trend). When stratified into three age groups, young females experienced significantly poorer survival than young males (DFS: hazard ratio [HR]=1.85 [1.04-3.30], OS: HR=2.65 [1.11-6.34]). After adjusting for tumor stage, site, differentiated grade and lymphatic or vascular invasion status, females ≤35 and >75 had shorter DFS than patients between 36 and 75 years old (HR=1.57 [1.03-2.38] and HR=1.51 [1.11-2.05, respectively]), while there was no difference in DFS between females ≤35 and those >75. For male patients, older age was associated with poorer OS after the same adjustment. CONCLUSION: Young female CRC patients (≤35 years old) had the poorest DFS and quite poor OS compared to the other age groups. This emphasizes the need for health care providers to have a heightened awareness and to conduct further research when caring for young female CRC patients.

[Endovascular repair of descending thoracic aortic aneurysm: preliminary experience].

OBJECTIVE: To report an initial experience with the endovascular repair of descending thoracic aortic aneurysm (DTAA). METHODS: Endoprostheses were placed into 41 patients with DTAA between January 2001 and July 2007 which were retrospectively analyzed. The preliminary right-left carotid and left carotid-subclavian bypass was performed in 4 cases in which the distances from the proximal aneurysm to the origin of the left common carotid artery were no longer than 15 mm. EVAR was conducted 1 week after the bypass or immediately. RESULTS: All stent grafts were deployed in proper position. There were two deaths (4.9%) during perioperative period, resulting from multiorgan failure and acute cardiac infarction, respectively. Eighteen endoleaks occurred immediately after EVAR (43.9%), four disappeared after balloon dilatation. There were two acute renal insufficiencies (4.9%), one requiring hemodialysis for more than 30 days. Follow-up, which ranged from 1 to 60 months [median, (18.6 +/- 4.2) months] was carried out in 26 patients (63.4%). Type-I endoleak and type-III endoleak were detected in two patients in 4 years and 2 years after EVAR, might because of migration, and were corrected using another stent-graft each. Two patients died of other diseases during follow-up. Complete thrombosis of the thoracic aneurysm sac with no late migration or endoleaks was revealed on CT at 3 months postoperatively in the remaining patients. The decrease in maximal aneurysm diameter was 0-22 mm [median, (8.3 +/- 4.5) mm] and the prosthetic vascular grafts in four patients with preliminary carotid subclavian bypass surgery were patent during the follow-up period. CONCLUSIONS: The treatment of descending thoracic aortic aneurysm with an endovascular approach is feasible with less trauma, quick recovery and less complications. It may offer the best means of therapy for high risk patients.

High preoperative peripheral blood neutrophil predicts poor outcome in rectal cancer treated with neoadjunctive chemoradiation therapy.

Distant metastasis impaired the value of neoadjunctive chemoradiation therapy (NCRT) for patients who were not pathological completed response. The objective of this study was to evaluate whether the absolute counts of preoperative neutrophils (pN) could predict survival outcomes of patients treated with NCRT. In this study, 289 locally advanced rectal cancer patients receiving NCRT and radical surgery were recruited between January 2006 and December 2012 at the Fudan University Shanghai Cancer Center. The absolute counts of pN were gathered and analyzed. Survival analysis was used to evaluate the prognostic value of pN. As results, a pN 3.00 was elected as the optimal cutoff points in term of survival by X-tile program. There were 112 patients (38.8%) in high-pN group and 177 patients (61.2%) in low pN group. The 4-year rectal cancer-specific survival (RCSS) and disease free survival (DFS) rate was 48.5% and 80.6%, 50.9% and 76.7% in high and low pN group, respectively. Univariate and multivariate analysis revealed that high-pN predicted poor RCSS and DFS. In conclusion, an elevated pN level was a significantly risk factor for locally advanced rectal cancer patient treated with NCRT, which may serve as a valuable marker to predict the outcomes of those patients.

Silencing of long non-coding RNA SBDSP1 suppresses tumor growth and invasion in colorectal cancer.

Long non-coding RNAs (lncRNAs) play critical roles in tumor development and progression. This study was undertaken to examine the expression and biological functions of a novel lncRNA SBDSP1 in colorectal cancer (CRC). Quantitative real-time PCR analysis was used to measure the expression of SBDSP1 in CRC tissues and cell lines. Knockdown of SBDSP1 via short hairpin RNA technology was performed to determine the roles of SBDSP1 in CRC cell growth, colony formation, cell cycle progression, migration, and invasion. The effect of SBDSP1 knockdown on tumorigenesis of CRC cells was investigated in a subcutaneous tumor mouse model. Western blot analysis was done to examine the involvement of signaling pathways in the action of SBDSP1. Notably, SBDSP1 was overexpressed in CRC tissues and cells relative to corresponding normal controls. Moreover, SBDSP1 expression was significantly greater in CRCs with nodal metastasis than in primary tumors (P=0.0259). Downregulation of SBDSP1 significantly inhibited cell proliferation, colony formation, migration, and invasion in SW480 and HCT116 cells, which was accompanied by suppression of Akt, ERK1/2, and STAT3 phosphorylation. SBDSP1-depleted cells showed a G0/G1 cell cycle arrest and deregulation of p21 and cyclin D1. In vivo studies confirmed that SBDSP1 downregulation retarded the growth of HCT116 xenogaft tumors. Altogether, SBDSP1 plays an essential role in CRC cell growth, invasion, and tumorigenesis, largely through inactivation of multiple signaling pathways. Therefore, targeting SBDSP1 may have therapeutic benefits in the treatment of CRC.