A number of circular RNAs (circRNAs) have been identified in various cancer including F-box and WD repeat domain containing 7 (FBXW7) circular RNA (circ-FBXW7), which can suppress glioma cell growth. ...However, the role of circ-FBXW7 in colorectal cancer (CRC) remains unclear. We aimed to investigate the effect and mechanisms of circ-FBXW7 on CRC progression.
The expression of circ-FBXW7 in CRC patients was detected by PCR. Stably knockdown of circ-FBXW7 (si circ-FBXW7) cell lines and overexpression of circ-FBXW7 (oe circ-FBXW7) cell lines were constructed by small interfering RNA method and plasmids transfection in CRC SW480 and SW620 cells. The functional experiments including cell proliferation, migration and invasion were carried out by cell counting kit-8 (CCK-8) assay, wound healing assay and trans well assay. The xenograft animal models were established to evaluate the effect and the underlying molecular mechanisms of circ-FBXW7 on CRC progression.
CRC samples had a significantly lower level of circ-FBXW7 compared to normal tissue. si circ-FBXW7 notably promoted the proliferation, colony formation, cell migration and invasion of CRC cell in vitro. On contrast, circ-FBXW7 overexpressed significantly suppressed CRC cell proliferation, migration and invasion. Similarly, si circ-FBXW7 stimulated the tumor growth and circ-FBXW7 overexpression repressed the tumor progression in SW480 and SW620 tumor models, which suggested that circ-FBXW7 could serve as a target biomarker of CRC. Further study found that si circ-FBXW7 up-regulated the mRNA and protein expressions of NEK2 and mTOR, and diminished the PTEN expression. Whereas, overexpressed circ-FBXW7 induced the tumor suppression via reversing the expressions of NEK2, mTOR, and PTEN.
circ-FBXW7 plays a major role in controlling the progression of CRC through NEK2, mTOR, and PTEN signaling pathways and may be a potential therapeutic target for CRC treatment. Circ-FBXW7 controls the progression of CRC through NEK2, mTOR, and PTEN signaling pathways and its overexpression inhibits colorectal cancer cell migration and invasion, suggesting the potential therapeutic target for CRC treatment.
Intestinal stem cells (ISCs) residing in the crypts are critical for the continual self-renewal and rapid recovery of the intestinal epithelium. The regulatory mechanism of ISCs is not fully ...understood. Here we report that CREPT, a recently identified tumor-promoting protein, is required for the maintenance of murine ISCs. CREPT is preferably expressed in the crypts but not in the villi. Deletion of CREPT in the intestinal epithelium of mice (Vil-CREPT
) results in lower body weight and slow migration of epithelial cells in the intestine. Vil-CREPT
intestine fails to regenerate after X-ray irradiation and dextran sulfate sodium (DSS) treatment. Accordingly, the deletion of CREPT decreases the expression of genes related to the proliferation and differentiation of ISCs and reduces Lgr5
cell numbers at homeostasis. We identify that CREPT deficiency downregulates Wnt signaling by impairing β-catenin accumulation in the nucleus of the crypt cells during regeneration. Our study provides a previously undefined regulator of ISCs.
Colon cancer remains one of the most common malignancies across the world. Thus far, a biomarker, which can comprehensively predict the survival outcomes, clinical characteristics, and therapeutic ...sensitivity, is still lacking.
We leveraged transcriptomic data of colon cancer from the existing datasets and constructed immune-related lncRNA (irlncRNA) pairs. After integrating with clinical survival data, we performed differential analysis and identified 11 irlncRNAs signature using Lasso regression analysis. We next plotted the 1-, 5-, and 10-year curve lines of receiver operating characteristics, calculated the areas under the curve, and recognized the optimal cutoff point. Then, we validated the pair-risk model in terms of the survival outcomes of the patients involved. Moreover, we tested the reliability of the model for predicting tumor aggressiveness and therapeutic susceptibility of colon cancer. Additionally, we reemployed the 11 of irlncRNAs involved in the pair-risk model to construct an expression-risk model to predict the prognostic outcomes of the patients involved.
We recognized a total of 377 differentially expressed irlncRNAs (DEirlcRNAs), including 28 low-expressed and 349 high-expressed irlncRNAs in colon cancer patients. After performing a univariant Cox analysis, we identified 115 risk irlncRNAs that were significantly correlated with survival outcomes of patients involved. By taking the overlap of the DEirlcRNAs and the risk irlncRNAs, we ultimately recognized 55 irlncRNAs as core irlncRNAs. Then, we established a Cox HR model (pair-risk model) as well as an expression HR model (exp-risk model) based on 11 of the 55 core irlncRNAs. We found that both of the two models significantly outperformed the commonly used clinical characteristics, including age, T, N, and M stages when predicting survival outcomes. Moreover, we validated the pair-risk model as a potential tool for studying the tumor microenvironment of colon cancer and drug susceptibility. Additionally, we noticed that combinational use of the pair-risk model and the exp-risk model yielded a more robust approach for predicting the survival outcomes of patients with colon cancer.
We recognized 11 irlncRNAs and created a pair-risk model and an exp-risk model, which have the potential to predict clinical characteristics of colon cancer, either solely or conjointly.
CXCL7 is an important chemoattractant cytokine, which signals through binding to its receptor CXCR2. Recent studies have demonstrated that the CXCL7/CXCR2 signaling plays a promoting role in several ...common malignancies, including lung, renal, colon, and breast cancer. However, the regulatory role of CXCL7, in cholangiocarcinoma, as well as the underlying mechanism, has not been previously reported. Herein, we found more positive expression of CXCL7 in cholangiocarcinoma tissues compared to adjacent non-tumor tissues. High CXCL7 expression was significantly correlated with poor differentiation, lymph node metastasis, vascular invasion and advanced clinical stage, but was not associated with age, gender, or tumor size. Besides, the expression of CXCL7 was significantly associated with the Ki67 expression, but not associated with CA199, AFP, or P53 expression in cholangiocarcinoma. Moreover, the overall survival of cholangiocarcinoma patients with high CXCL7 expression was significantly shorter than those with low CXCL7 expression. In vitro study indicated that CXCL7 and CXCR2 were also positively expressed in several common cholangiocarcinoma cell lines, including HuCCT1, HuH28, QBC939, EGI-1, OZ and WITT. SiRNA-induced inhibition of CXCL7 significantly reduced the proliferation and invasion of QBC939 cells. On the contrary, overexpression of CXCL7 markedly promoted these malignant phenotypes of QBC939 cells. Of note, the conditioned medium of CXCL7-overexpresing human hepatic stellate cells could also promote the proliferation and invasion of QBC939 cells, suggesting that CXCL7 may also play an oncogenic role in cholangiocarcinoma in a paracrine-dependent manner, not only in an autocrine-dependent manner. Molecular assay data suggested that the AKT signaling pathway was involved in the CXCL7-mediated malignant phenotypes of QBC939 cells. In summary, our study suggests that CXCL7 plays a promoting role in regulating the growth and metastasis of cholangiocarcinoma.
Background and Aims
Robotic-assisted right hemicolectomy (RARH) has many benefits in treating colon cancer, but it is a new technology that needs to be evaluated. This study aims to assess the ...learning curve (LC) of RARH procedures with the complete mesoscopic exception and D3 lymph node dissection for colon carcinoma.
Methods
A retrospective analysis was performed on a consecutive series of 76 patients who underwent RARH from July 2014 to March 2018. The operation time was evaluated using the cumulative sum (CUSUM) method to analyze the LC. The patients were categorized into two groups based on the LC: Phase I and Phase II. Statistical methods were used to compare clinicopathological data on intraoperative and perioperative outcomes at different stages of the study.
Results
The peak point of the LC was observed in the 27th case. Using the CUSUM method, we divide the LC into two stages. Stage 1 (initial learning stage): Cases 1–27 and Stage 2 (proficiency phase): Cases 28–76. There were no obvious distinctions between the two patients’ essential characteristics (age, sex, body mass index, clinical stage, and ASA score). The mean operation time of each group is 187.37 ± 45.56 min and 161.1 ± 37.74 min (
P
= 0.009), respectively. The intraoperative blood loss of each group is 170.4 ± 217.2 ml and 95.7 ± 72.8 ml (
P
= 0.031), respectively.
Conclusion
Based on the LC with CUSUM analysis, the data suggest that the learning phase of RARH was achieved after 27 cases. The operation time and the intraoperative blood loss decrease with more cases performed.
Signal transducer and activator of transcription 3 (STAT3) has been shown to upregulate gene transcription during tumorigenesis. However, how STAT3 initiates transcription remains to be exploited. ...This study is to reveal the role of CREPT (cell cycle-related and elevated-expression protein in tumours, or RPRD1B) in promoting STAT3 transcriptional activity.
BALB/c nude mice, CREPT overexpression or deletion cells were employed for the assay of tumour formation, chromatin immunoprecipitation, assay for transposase-accessible chromatin using sequencing.
We demonstrate that CREPT, a recently identified oncoprotein, enhances STAT3 transcriptional activity to promote tumorigenesis. CREPT expression is positively correlated with activation of STAT3 signalling in tumours. Deletion of CREPT led to a decrease, but overexpression of CREPT resulted in an increase, in STAT3-initiated tumour cell proliferation, colony formation and tumour growth. Mechanistically, CREPT interacts with phosphorylated STAT3 (p-STAT3) and facilitates p-STAT3 to recruit p300 to occupy at the promoters of STAT3-targeted genes. Therefore, CREPT and STAT3 coordinately facilitate p300-mediated acetylation of histone 3 (H3K18ac and H3K27ac), further augmenting RNA polymerase II recruitment. Accordingly, depletion of p300 abolished CREPT-enhanced STAT3 transcriptional activity.
We propose that CREPT is a co-activator of STAT3 for recruiting p300. Our study provides an alternative strategy for the therapy of cancers related to STAT3.
The incidence of colorectal cancer increases with aging. Curative-intent surgery based on a minimally invasive concept is expected to bring survival benefits to elderly patients (aged over 80 years) ...with colorectal cancer who are frequently with fragile health status and advanced tumors. The study explored survival outcomes in this patient population who received robotic or laparoscopic surgery and aimed to identify an optimal surgical option for those patients.
We retrieved the clinical materials and follow-up data on elderly patients with colorectal carcinoma who received robotic or laparoscopic surgery in our institution. The pathological and surgical outcomes were compared to examine the efficacy and safety of the two approaches. The DFS (disease-free survival) and OS (overall survival) results at 3 years after surgery were assessed to explore the survival benefits.
A total of 111 patients were screened for the study, including 55 in the robotic group and 56 in the laparoscopic group. The demographic details were generally similar between the two groups. No statistically significant difference in the number of removed lymph nodes was observed between the two approaches, with a median of 15 versus 14 (P = 0.053). The intraoperative blood loss was significantly reduced by robotic technique when compared to the laparoscopic approach, with a mean of 76.9 ml versus 161.6 ml (P = 0.025). There were no significant differences in operation time, conversion, postoperative complications and recovery, and long-term outcomes between the two groups.
Robotic surgery was prized for elderly patients with colorectal cancer who developed anemia and/or hematological conditions.
Aspartoacylase (ASPA) is a gene that plays an important role in the metabolic reprogramming of cancer. However, the clinical relevance of ASPA in gastric cancer (GC) has not been demonstrated.
The ...link between ASPA and the clinical features of GC was determined using two public genomic databases. The multivariate Cox proportional hazard model and generalised linear regression model were applied to examine whether the ASPA level is associated with the prognosis and other pathological factors. In addition, the role of specific genes in the infiltration of immune cells in the setting of GC was investigated using a further immunological database. The expression level of various proteins was detected using a western blotting assay. Transwell and methyl thiazolyl tetrazolium tests were applied for the detection of cellular invasion and proliferation, with small hairpin ribonucleic acid used to knockdown ASPA.
According to the multivariate Cox regression results, the down-regulated ASPA expression is a distinct prognostic factor. Furthermore, ASPA has significant positive correlations with the infiltration of immune cells in GC lesions. Compared to the non-cancer tissues, the GC tissues had a significantly lower level of ASPA expression (p < 0.05). Using knockdown and overexpression techniques, it was demonstrated that ASPA affects the capacity of cell lines for GC to both proliferate and invade.
Overall, ASPA could promote the occurrence and development of GC and presents a promising predictive biomarker for the disease since it is favourably connected with immune infiltrates and negatively correlated with prognosis.
Background
Robotic colorectal cancer surgery is widely accepted and applied. However, there is still no objective and comprehensive assessment on the data of nationwide multicenter series.
Method
A ...total of 28 medical centers in Mainland China participated in this nationwide retrospective observational study. From the first case performed in each center to the last until December 2017, patients with robotic resection for primary tumor and pathologically confirmed colorectal adenocarcinoma were consecutively enrolled. Clinical, pathological and follow-up data were collected and analyzed.
Results
A total of 5389 eligible patients were finally enrolled in this study, composing 72.2% of the total robotic colorectal surgery volume of Mainland China in the same period. For resections of one bowel segment of primary tumor, the postoperative mortality rate was 0.08% (4/5063 cases), and the postoperative complication rate (Clavien–Dindo grade II or higher) was 8.6% (434/5063 cases). For multiple resections, the postoperative mortality rate was 0.6% (2/326 cases), and the postoperative complication rate was 16.3% (53/326 cases). Out of 2956 patients receiving sphincter-preserving surgery in only primary resection, 130 (4.4%) patients had anastomotic leakage. Traditional low anterior resection (tumor at middle rectum) (OR 2.384,
P
< 0.001), traditional low anterior resection (tumor at low rectum) (OR 1.968,
P
= 0.017) and intersphincteric resection (OR 5.468,
P
= 0.006) were significant independent risk factors for anastomotic leakage. Female gender (OR 0.557,
P
= 0.005), age ≥ 60 years (OR 0.684,
P
= 0.040), and preventive stoma (OR 0.496,
P
= 0.043) were significant independent protective factors. Body mass index, preoperative chemotherapy/radiotherapy, tumor size, and TNM stage did not independently affect the occurrence of anastomotic leakage.
Conclusion
Robotic colorectal cancer surgery was safe and reliable and might have advantages in patients at high risk of anastomotic leakage.
Overall, gastric cancer prognosis remains poor. Detailed characterization of molecular markers that govern gastric cancer pathogenesis is warranted to establish innovative therapeutic options. HIF-1α ...overexpression has been linked to poor gastric cancer prognosis. However, though researched for years, the prognostic role of HIF-1α in gastric cancer is still controversial. Hence, the objective of the present study was to analyze the prognostic values of HIF-1α, TGF-β, VEGF and pERK1/2 in gastric cancer patients following gastrectomy.
This study included 446 patients with confirmed gastric cancer who underwent gastrectomy in a single Chinese Cancer Center between 2005 and 2006. Clinicopathologic features, as well as immunohistochemical analysis of TGF-β, HIF-1α, VEGF and pERK1/2 were determined. Long-term survival of these patients was analyzed using univariate and multivariate analyses.
HIF-1α overexpression was more frequent in patients with hepatic metastases (71.6% versus 43.0% in those without hepatic metastases, P = 0.000, χ2 = 23.086) and more frequent in patients with peritoneum cavity metastasis (62.3% versus 43.0% in those without such metastasis, P = 0.000, χ2 = 13.691). In univariate analysis, patients with HIF-1α overexpression had a shorter disease-free survival (DFS) and overall survival (OS) than patients with weak-expression (DFS: NA VS. 16.8 m, P = 0.000, χ2 = 74.937; OS: NA VS. 25.5 m, P = 0.000, χ2 = 90.594). Importantly, HIF-1α overexpression was a promising prognostic marker for poor survival by multivariate analysis (DFS: HR 2.766, 95%CI 2.136-2.583, P = 0.000; OS: HR 3.529, 95%CI 2.663-4.667, P = 0.000).
HIF-1α overexpression could be considered a useful independent prognostic biomarker in gastric cancer after gastrectomy, and is correlated to both a poor overall survival and disease-free survival in these patients. HIF-1α expression can be used to stratify patients at higher risk for poor prognosis, and is potentially an important therapeutic target in gastric cancer patients.
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