The Role of circRNAs in the Diagnosis of Colorectal Cancer: A Meta-Analysis.

Background: A novel category of non-coding circular RNAs (circRNAs) has been found to be dysregulated in colorectal cancer (CRC) and significantly contribute to its progression. However, the feasibility of using circRNA as a diagnostic biomarker for CRC remains to be elucidated. Herein, we aimed to comprehensively collect and analyze evidence regarding the potential application of circRNAs as diagnostic indicators for CRC. Methods: A comprehensive retrieval of relevant studies dating from January, 2015 to December 2020, was carried out in PubMed, Cochrane Library, and Web of Science. Data regarding the diagnostic accuracy of circRNA for CRC, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC), were obtained from the included studies. Quality assessment of diagnostic accuracy studies (QUADAS-2) was used to assess the methodological quality of each study. Statistical analysis was performed using STAT and RevMan software. Results: Eighteen studies, involving a total of 2021 individuals, were included in the present meta-analysis. The specimens examined included tissue, serum, and plasma. The pooled sensitivity, specificity, DOR, PLR, NLR, and AUC, with a 95% confidence interval (CI), of circRNAs in the diagnosis of CRC were 0.78 (0.71-0.83), 0.73 (0.68-0.78), 9.68 (6.76-13.85), 2.92 (2.45-3.50), 0.30 (0.23-0.39), and 0.81 (0.78-0.85), respectively. Subgroup analysis showed that the upregulated circRNAs in the tissue or plasma possessed relatively higher diagnostic values for CRC than the downregulated circRNAs. There was no significant difference between the tissue-derived and non-tissue-derived circRNA subgroups. Conclusion: circRNA may be used as a diagnostic biomarker for CRC because of its relatively high diagnostic accuracy in distinguishing CRC patients from normal controls. Further prospective studies are needed to identify more representative circRNAs as diagnostic markers for CRC.

KIF3B Promotes the Proliferation of Pancreatic Cancer.

Background: Kinesin Family Member 3B (KIF3B) is one of the most ubiquitously expressed KIFs, which is related to numerous physiological responses. KIF3B has also been implicated in carcinogenesis such as in hepatocellular carcinoma cells. However, the expression of KIF3B has not been studied in pancreatic cancer along with its clinical significance. Methods: Immunohistochemical assays were performed to detect the expression levels of KIF3B in the tumor tissues and adjacent non-tumor tissues. Patients were sequentially divided into different expression levels of KIF3B group based on the staining intensity of FKIF3B in tumor tissues. The link between KIF3B expression and clinical characteristics were investigated, and the role of KIF3B on pancreatic cancer cell proliferation was detected by colony formation and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, respectively. And the proliferation related proteins such as Ki67 and proliferating cell nuclear antigen (PCNA) were detected by Western blot. The possible effects of KIF3B on tumor growth were assessed in vivo. Results: KIF3B was highly expressed in human pancreatic cancer tissues. We also found KIF3B was significantly associated to the pTNM stage (*p = 0.018), lymph node metastasis (*p = 0.040) and vascular invasion (*p = 0.034). We reported that increased expression of KIF3B was significantly correlated with poor clinical outcome in our clinical cohort of pancreatic cancer. Furthermore, functional assays revealed that knockdown KIF3B in vitro and in vivo might inhibit cancer cells proliferation by affecting Ki67 and PCNA. Conclusions: Our data suggested that KIF3B was associated with pancreatic cancer malignant progression especially proliferation. Hence, KIF3B might serve as a potential therapy target of pancreatic cancer in clinical treatment.

The diagnostic and prognostic value of CHFR hypermethylation in colorectal cancer, a meta-analysis and literature review.

The Checkpoint with Forkhead-associated and Ring finger domains (CHFR) is a mitotic checkpoint and tumor-suppressor gene, its loss contributes tumorigenesis of epithelial cancers including colorectal carcinoma (CRC). The diagnostic and prognostic value of CHFR promoter hypermethylation in CRC remains unclear. This study aimed to conduct a meta-analysis and literature review and investigate clinicopathological significance of CHFR promoter hypermethylation in CRC. The following online database were used: PubMed, EMBASE, and Web of Science up to March 2017. Odds Ratios (OR) and Hazard Ratios (HR) with 95% corresponding confidence intervals (CIs) were calculated. A total of seven relevant articles were available for meta-analysis which included 966 patients. The frequency of CHFR promoter hypermethylation significantly increased in CRC compared to normal colorectal mucosa tissue, pooled OR was 8.35, p < 0.00001. CHFR promoter hypermethylation was not significantly correlated to stage, OR was 1.16, p = 0.63. However, CHFR promoter hypermethylation was more frequently observed in CRC with positive lymph nodes metastasis than CRC with negative lymph nodes metastasis, OR was 0.46, p = 0.03. Additionally CHFR promoter hypermethylation was significantly related to poor overall survival in patients with CRC, HR was 0.62, p = 0.008. Based on these results, tumor CHFR promoter hypermethylation is not only a diagnostic biomarker for CRC, but also a prognostic marker. CHFR promoter hypermethylation is significantly associated with worse overall survival in patients with CRC. Our data suggested that CHFR could be a potential drug target for development of demethylation treatment for patients with CRC.

APC hypermethylation for early diagnosis of colorectal cancer: a meta-analysis and literature review.

Adenomatous polyposis coli (APC) promoter hypermethylation has been frequently observed in colorectal cancer (CRC). The association between APC promoter methylation and clinicopathological significance in CRC is under investigation. We performed a meta-analysis to quantitatively evaluate the significance of APC methylation in CRC. The study included a total of 24 articles and 2025 CRC patients. The frequency of APC promoter hypermethylation was significantly higher in colorectal adenoma than in normal colorectal tissue, OR was 5.76, 95% CI, 2.45-13.56; p<0.0001, I2=0%. APC promoter more frequently hypermethylated in CRC stage I compared to normal colorectal tissue, OR was 13.42, 95% CI, 3.66-49.20; p<0.0001, I2=31%. The risk of incidence of CRC was significantly correlated to APC promoter hypermethylation, pooled OR was 9.80, 95%CI, 6.07-15.81; p<0.00001, I2=43%. APC methylation was not associated with grade, stage of CRC as well as tumor location, patients' gender, and smoking behavior. The results indicate that APC promoter hypermethylation is an early event in carcinogenesis of CRC, could be a valuable diagnostic marker for early-stage CRC. APC methylation is not significantly associated with overall survival in patients with CRC. APC is a potential drug target for development of personalized treatment.

miR-203 promotes proliferation, migration and invasion by degrading SIK1 in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDA) is among the most lethal human cancers and it is insensitive to many chemotherapeutic drugs. The molecular basis of pancreatic cancer remains to be elucidated. Investigations into the molecular mechanism involved in the development and progression as well as drug resistance of the disease may be useful to understand the pathogenesis and progression of the disease and offer new targets for effective therapies. In the present study, we showed that salt-inducible kinase 1 (SIK1) was downregulated and loss of SIK1 was associated with gemcitabine resistance in pancreatic cancer. In pancreatic cancer cells, SIK1 inhibited proliferation, migration and invasion. An analysis of potential microRNA target sites was performed using the prediction algorithms, miRanda, TargetScan and PicTar. The three algorithms predicted that miR-203 is capable of targeting 3'UTR of SIK1. Subsequent experiments confirmed the prediction. In addition, the results showed that miR-203 promotes proliferation, migration and invasion in pancreatic cancer cells, whereas the restoration of SIK1 abrogated the regulation of pre-miR­203-mediated proliferation, migration and invasion.

Surgical management for carcinoma of the gallbladder: a single-institution experience in 25 years.

BACKGROUND: Gallbladder carcinoma is rare and associated with dismal outcomes. Radical surgery is the only curative treatment, and options for adjuvant therapy remain limited. This study aimed to determine the factors influencing outcome of treatment in patients with gallbladder carcinoma, and to identify the patients who might benefit from radical surgery and adjuvant therapy. METHODS: Medical records and follow-up histories of 150 patients with gallbladder carcinoma who had undergone surgery between April 1980 and December 2005 were retrospectively reviewed. The factors predictive for the survival of the patients were identified using multivariate analysis. RESULTS: Surgery for gallbladder cancer was associated with an overall 5-year survival rate of 26.2%. After curative resection (40% of the patients), the 5-year survival rate was 60.3%. The patients who underwent R0 resection had a significantly longer median survival (97.3 months) than those who had R1/R2 resection (8.3 months) or only laparotomy (3.7 months) (P < 0.0001). Univariate analysis showed that resectability, American Joint Committee on Cancer staging, tumor grade, adjuvant therapy, jaundice at presentation, depth of tumor invasion, lymph node involvement, distant metastasis, and carcinoembryonic antigen level were statistically significant predictors for survival. Multivariate analysis revealed American Joint Committee on Cancer staging and resectability were independent prognostic factors for survival. The patients who underwent noncurative resection might benefit from adjuvant therapy (median survival, 12.4 months vs 7.2 months, P = 0.006). CONCLUSIONS: Favorable survival rate can be achieved after curative resection, even for selected patients with advanced disease. Adjuvant therapy may improve the survival of patients with gallbladder carcinoma.

[Simultaneous liver and colorectal resection for synchronous colorectal liver metastasis].

OBJECTIVE: To investigate the safety and long term outcome of simultaneous liver and colorectal resection for synchronous colorectal liver metastasis. METHODS: Forty-three synchronous colorectal liver metastasis patients who received simultaneous colectomy and hepatectomy between May 1981 and November 2005 were analyzed retrospectively. RESULTS: The group included 21 male patients and 22 female patients, with the median age of 52 years. The overall median operative time was 180 minutes, 30 cases received blood transfusion, and the median volume was 800 ml. The median hospital stay was 15 days. The morbidity and mortality was 18.6% and 2.3%, respectively. The overall median survival time was 25 months, 5-year survival rate was 19.1%. The survival of patients underwent R0 resection were substantially better (median survival time 48 months, 5-year survival rate 33.8%) than that of the patients who did not undergo R0 resection (20 months, 7.6%) (P = 0.002). CONCLUSIONS: Simultaneous liver and colorectal resection is safe and effective for synchronous colorectal liver metastasis. Furthermore, simultaneous R0 resection should be the optimal surgery for the resectable cases.

[Outcome of surgical therapy for liver metastasis of colorectal cancer: analysis of 75 cases].

OBJECTIVE: To explore the strategy to improve the long term survival of liver metastasis of colorectal cancer after surgical treatment. METHODS: The clinical data of 75 patients with liver metastasis of colorectal cancer, 43 males and 32 females, aged 51.4, who received hepatectomy between January 1981 and November 2005, were analyzed. RESULTS: The primary tumor site was colon in 39 cases, and rectum in 36 cases. Liver metastasis was synchronous in 59 patients, and metachronous in 16 patients. 45 patients received simultaneous liver and colorectal resection, 29 patients received metachronous resection, and 1 patient did not receive primary rectal cancer resection. The operative complication rate and the mortality were 16% (12/75) and 1.33% (1/75) respectively. The overall 1- 3-, and 5-year survival rates were 86.7%, 35.5%, and 22.2% respectively, and the median survival time was 25 months. There were residual tumors in 35 patients. The 1-, 3-, and 5-year survival rates of the residual tumor group were 80.6%, 5.4%, and 5.4% respectively, all significantly lower than those of the radical resection group (91.6%, 58.1%, and 34.9% respectively, and the median survival time of the residual tumor group was 18 months, significantly shorter than that of the radical resection group (38 months) (all P = 0.000). CONCLUSION: Surgical resection of liver metastasis of colorectal cancer significantly prolongs the survival time, and resection of all liver deposits and the extrahepatic disease is the most important factor influencing survival.

[Clinicopathological features and surgical treatment of familial adenomatous polyposis].

OBJECTIVE: To investigate the clinicopathological features and surgical treatment of familial adenomatous polyposis (FAP). METHODS: The clinical data of 51 patients with FAP, 29 males and 22 females, aged 36.6 (17-67), hospitalized Sep 1980-Dec 2005 were analyzed. RESULTS: Twenty-nine patients had family history of FAP and 7 of them were discovered during screened because of family history. The main clinical manifestations included rectal bleeding or bloody stool, diarrhea, abdominal pain, and general discomfort in the abdomen. Synchronous malignant changes were found in 28 patients while hospitalized. The incidence of colorectal cancer was 54.9%. The average age of those with colorectal cancer was 40.5 and the age of those without colorectal cancer was 31.9. 81.8% of the colorectal cancers occurred on the rectum and sigmoid colon. Different types of proctocolectomy were performed on 50 patients, and one patient received only pelvic radiotherapy. The follow-up rate was 74.5%. Only 27.5% of the patients received regular surveillance. Colorectal cancer was found in 8 patients after the first operation. So far 17 patients died. CONCLUSIONS: There were no specific clinical manifestations for FAP. Colonoscopy is the most important diagnostic procedure. Surgical treatment should be given as soon as possible. The specific operation type should be based on the individual aspects of patients. Life-time surveillance and follow-up are very important.