Clinical analysis of ultrasound-guided radiofrequency ablation for recurrent colorectal liver metastases after hepatectomy.

BACKGROUND: RFA is designed to produce localized tumor destruction by heating the tumor and surrounding liver tissue, especially suitable for patients who do not qualify for hepatic resection. Many studies have reported that RFA was inferior to hepatectomy in the treatment of recurrent colorectal liver metastases. However, strong evidence is lacking in the literature. This study aimed to investigate the effect and clinical outcome of percutaneous ultrasound-guided RFA and repeat hepatic resection for recurrent colorectal liver metastases after hepatectomy. METHODS: From January 2007 to January 2014, 194 patients with recurrent colorectal liver metastases after hepatectomy diagnosed in our hospital was performed, and then divided into two groups based on different regimens: repeat hepatic resection group and RFA group. The clinical data of the two groups were analyzed. After treatment, the liver function-related indexes, complication rate, survival rate, and tumor recurrence of the two groups were recorded. The difference in short-term and long-term effects between repeat hepatic resection and RFA was identified by propensity score analysis. RESULTS: The number of metastases and the proportion of left and right lobe involved by tumor and preoperative chemotherapy in the RFA group were higher than those in the repeat hepatic resection group. The clinical data showed no significant difference between the two groups after using propensity score analysis. Compared with the RFA group, the liver function of the repeat hepatic resection group was significantly improved. After adjustment for potential confounders, no significant difference in liver function-related indexes was found between RFA and repeat hepatic resection, and the incidence of complications in the RFA group was lower. In survival analysis, there was no significant difference in OS and DFS between the two groups. CONCLUSIONS: RFA is a safe and effective therapeutic option for patients with recurrent colorectal liver metastases after hepatectomy.

The long noncoding RNA TPTE2P1 promotes the viability of colorectal cancer cells.

Long noncoding RNAs (lncRNAs) have important functions in tumor development and progression, including colorectal cancer (CRC), but their roles are not completely understood. In this study, the roles of the lncRNA transmembrane phosphoinositide 3-phosphatase and tensin homolog 2 pseudogene 1 (TPTE2P1), previously implicated in gallbladder cancer cell migration and invasion, were evaluated in CRC. In particular, quantitative polymerase chain reaction was used to quantify TPTE2P1 levels in tumor tissues and cell lines. The association between TPTE2P1 and survival was analyzed using the online tool OncoLnc. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, colony formation assays, and flow cytometry were used to evaluate the effects of TPTE2P1 on viability, cell cycle progression, and apoptosis. Signaling pathway proteins were quantitated by Western blot analysis. Finally, the role of TPTE2P1 was analyzed in vivo using mouse models. TPTE2P1 levels were significantly higher in CRC tissues than in adjacent normal tissues. Higher expression was associated with a poor survival rate. The silencing of TPTE2P1 led to cell cycle arrest at the S phase and thereby inhibited cell viability. TPTE2P1 knockdown also caused cancer cell apoptosis via the activation of the apoptosis regulator (BCL2)/caspase 3 signaling cascade. In addition, the inhibition of TPTE2P1 had suppressive effects on tumors in vivo. TPTE2P1 is upregulated in CRC and plays essential roles in the regulation of cell viability in vitro and tumor formation in vivo.

Long non-coding RNA PVT1 functions as an oncogene in human colon cancer through miR-30d-5p/RUNX2 axis.

PURPOSE: Recently, long noncoding RNAs (lncRNAs) have caught more attention for their role in tumor progression. Colon cancer is one of these ordinary malignant tumors. This study aimed to identify how lnc RNA PVT1 affects the progression of colon cancer. METHODS: PVT1 expression of both colon cancer cell tissue and 60 paired cancer and peri-tumoral tissue samples was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The associations between lnc RNA PVT1 expression level and clinicopathological characteristics and patients' disease-free survival rate were evaluated. Furthermore, function assays containing cell proliferation assay, colony formation and transwell assay were conducted. Mechanism-associated experiments included western blot assay, luciferase assay and RNA immunoprecipitation assay. RESULTS: PVT1 expression was significantly higher in tumor tissues than in peritumoral tissues, and was associated with lymph node metastasis, tumor stage and survival time of these patients. Moreover, knockdown of PVT1 promoted tumor growth and invasion in vitro. In addition, further experiments revealed that miR-30d-5p was a direct target of PVT1 and its expression in tumor tissues negatively correlated to PVT1 expression. Moreover, RUNX2 was identified as the direct target spot of miR-30d-5p according to the mechanism experiments. Besides, RUNX2 expression was positively correlated with PVT1 in cancer tissues and cells. CONCLUSIONS: These results indicate that PVT1 could promote metastasis and proliferation of colon cancer via suppressing miR-30d-5p/RUNX2 axis, which may offer a new way for interpreting the mechanism of colon cancer development.

The potential roles of gut microbiome in anal fistula.

Anal fistula is a common proctological disease, but the thorough mechanisms of the anal fistula formation are still unclear. An increasing number of studies have revealed the crucial role of gut microbiota in intestinal diseases. We used 16S rRNA gene sequencing to analyze the intestinal microbiome in order to determine whether there are differences in the microbiome between anal fistula patients and healthy individuals. The microbiome samples were extracted by repeatedly wiping the rectal wall with intestinal swab. Before this operation, the whole intestine of all participants was irrigated and the score of the Boston bowel preparation scale reached 9. The biodiversity of gut microbiome of rectum revealed significant difference between anal fistula patients and healthy individuals. 36 discriminative taxa were identified by LEfSe analysis between two groups. At the phylum level, Synergistetes was enriched in anal fistula patients, while Proteobacteria was higher in healthy individuals. We also found that at the genus level, Blautia, Faecalibacterium, Ruminococcus, Coprococcus, Bacteroides, Clostridium, Megamonas and Anaerotruncus were highly enriched in anal fistula patients, while the microbiome of healthy individuals was enriched with Peptoniphilus and Corynebacterium. Spearman correlations showed the extensive and close association among genera and species. Finally, a diagnostic prediction model was constructed by random forest classifier, and the area under curve (AUC) reached 0.990. This study gave an important hint for analyzing gut microbiome of rectum in anal fistula patient.Keypoints.We use the 16S rRNA gene sequencing to test the microbiome samples extracted from the intestinal swab. This is the first study to explore the gut microbiome of rectum using this workflow. We also found the distinct gut microbiome of rectum differences between anal fistula patients and healthy individuals.

Overexpression of microRNA-203 can downregulate survivin and function as a potential therapeutic target in papillary thyroid cancer.

Papillary thyroid cancer (PTC) is the most common type of thyroid carcinoma. PTC has a considerably high five-year survival rate; however, the possibility of recurrence is also high. Therefore, there is a requirement to clarify the molecular mechanism of PTC to promote understanding regarding the development of the disease and further improve prognosis. A number of studies have demonstrated that microRNAs (miRNAs or miRs) contribute to the progression of PTC. The present study revealed that the expression level of miR-203 was significantly lower in PTC tissues and cell lines compared with in the normal controls. In addition, inhibition of miR-203 was identified to be associated with an overexpression of survivin, which was observed in PTC samples. miR-203 regulates the expression of Bcl-2 via its downstream regulator survivin. Furthermore, the present study identified that inhibition of miR-203 histone acetylation was associated with high expression levels of miR-203 in PTC tissue samples. In summary, the results indicate that miR-203 functions as a biomarker and may serve as a candidate target for the development of novel therapeutic strategies to treat PTC.

High expression of CDH3 predicts a good prognosis for colon adenocarcinoma patients.

Colon adenocarcinoma (COAD) is one of the most common types of malignancy of the digestive system, and a better understanding of the molecular mechanisms will contribute to an improvement in the quality of life for COAD patients. Cadherin 3 (CDH3), a gene encoding P-cadherin, is a major component of adherens junctions and is closely associated with the occurrence and development of a variety of tumor types. However, the current knowledge regarding the role of CDH3 in COAD is limited. The present study aimed to identify the relative mRNA and protein expression levels of CDH3 in COAD tissues, and whether CDH3 had any influence on the survival rate of patients with COAD. Analysis of differentially expressed genes using the UALCAN database revealed that CDH3 was significantly upregulated in COAD tissues, and reverse transcription-quantitative PCR analysis further confirmed that CDH3 was upregulated in 48 COAD tissues compared with that in their paired normal tissues (n=48). Consistent with this, analysis of the Human Protein Atlas database indicated that the expression levels of the CDH3 protein were upregulated in COAD tissues (n=11) compared with those in normal tissues (n=3; P=0.0245). Next, the association between the mRNA levels of CDH3 and the survival rate of the COAD patients was analyzed using the UALCAN database, and the Kaplan-Meier curves revealed that the CDH3 high expression group (n=69) had a better overall survival compared with that of the CDH3 medium/low expression group (n=210; P=0.037). Furthermore, analysis of clinical data of a cohort from our hospital indicated that the median survival time for COAD patients with high (n=20) and low (n=20) CDH3 levels was 55.5 and 43.5 months, respectively, and there was a significant difference in the survival time between the two groups (P=0.0078). The above results verified that CDH3 was significantly upregulated in the COAD tissues and that high expression of CDH3 predicts a good prognosis for COAD patients.

[Distribution characteristics and risk factors of colorectal adenomas].

OBJECTIVE: To determine the detection rate and distribution characteristics of colorectal adenomas in Ningbo area of China, and to identify the risk factors for colorectal adenoma, in order to provide reference for colorectal cancer screening. METHODS: A cross-sectional study was performed among 8660 subjects undergoing colonoscopy in the Ningbo No.2 Hospital between January and December 2016, using a questionnaire, including demographic data (age, gender, height and weight), history of diseases (diabetes, hypertension, hyperlipidemia, and family history of malignant neoplasm), lifestyle (smoking, alcohol, dietary bias on red meat, dietary bias on fruit and vegetables, dietary frequency of pickled food and physical activities), and intestinal early warning symptoms. All colonoscopically detected polyps were removed for histological examination. Polyps were histologically divided into non-adenomatous (hyperplastic polyps and inflammatory polyps) and adenomatous polyps (tubular, villous, tubulovillous and serrated adenomas). Pathologic features were analyzed according to anatomical site. Multivariate logistic regression analysis was used to identify the risk factors for colorectal adenoma. RESULTS: A total of 7077 subjects who received colonoscopic examination and completed the questionnaire survey were enrolled in this study. There were 3633 males and 3444 females with a median age of 53 (ranged 17 to 83) years. Adenoma detection rate was 15.6% (1103/7077) in all cases, 21.0%(762/3633) for males, and 9.9%(341/3444) for females(P=0.000). Detection rate of 6.2%(29/469) was recorded in individuals aged less than 30 years, 8.0%(87/1086) in those from 30 to 39 years, 12.1%(148/1222) in those from 40 to 49 years, 16.8%(272/1623) in those from 50 to 59 years, 20.4%(326/1601) in those from 60 to 69 years, and 22.4%(241/1076) in those ≥70 years. The detection rate increased according to age(P=0.000). A total of 1521 adenomas were detected in 1103 cases, including 1455 tubular adenomas, 33 tubulovillous adenomas, 9 villous adenomas and 24 serrated adenomas. Among 1521 adenomas, 44.1%(n=671) located in the right hemicolon, 39.0%(n=593) in the left hemicolon, and 16.9%(n=257) in the rectum. Significantly larger number of serrated adenomas and advanced adenomas (advanced adenoma was defined as any adenoma with high-grade intraepithelial neoplasia, diameter ≥10 mm or with villous component) was observed in the right hemicolon compared to left hemicolon and rectum [serrated adenomas: 2.5%(17/671) vs. 0.8% (5/593) and 0.8% (2/257), P=0.029; advanced adenoma: 9.2% (62/671) vs. 5.2% (31/953) and 6.6% (17/257), P=0.021]. Multivariate analysis showed that malely (P=0.003), elderly (P=0.000), obesity (P=0.014), smoking (P=0.001), alcohol (P=0.032), and family history of malignancy (P=0.000) were independent risk factors of colorectal adenoma. CONCLUSIONS: In view of a higher detection rate of colorectal adenoma in population aged 40 to 49 years especially in male individuals, the starting age of colonoscopy screening may be advanced to 40 years old. People with family history of malignancy, obesity, and habit of smoking or drinking should be regarded as important subjects for colonoscopy screening. During colonoscopy screening, special emphasis should be given to right hemicolon.

Identification of candidate genes and long non-coding RNAs associated with the effect of ATP5J in colorectal cancer.

The incidence and development of colorectal cancer (CRC) is a process with multiple gene interactions. We have previously demonstrated that ATP synthase-coupling factor 6, mitochondrial (ATP5J) is associated with CRC migration and 5-fluorouracil resistance; nevertheless, the exact molecular mechanism remains unclear. The following study uses microarray and bioinformatics methods to identify candidate genes and long non-coding RNAs (lncRNAs) in CRC cells (two pairs) with upregulated and downregulated ATP5J. Briefly, a total of 2,190 differentially expressed mRNAs (DEmRNAs) were sorted. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed for 4 DEmRNAs to validate the results of microarray analysis. Functional annotation and pathway enrichment were analyzed for DEmRNAs using the Database for Annotation, Visualization and Integrated Discovery. Significantly enriched pathways included the regulation of gene expression and cell growth. The protein­protein interaction network was constructed, and AKT serine/threonine kinase 2 (AKT2) was considered as one of the hub genes. For further analysis, 51 DEmRNAs and 30 DElncRNAs were selected that were positively or negatively associated with the expression of ATP5J in the two cell pairs. X-inactive specific transcript (XIST), premature ovarian failure 1B (POF1B) and calmin (CLMN) were identified in the DEmRNA-DElncRNA co-expression network. The expression of AKT2 and XIST in CRC cells was confirmed by RT-qPCR. To sum up, the candidate genes and lncRNAs, as well as potential signaling pathways, which were identified using integrated bioinformatics analysis, could improve the understanding of molecular events involved in the function of ATP5J in CRC.

Knockdown of stromal interaction molecule 1 inhibits proliferation of colorectal cancer cells by inducing apoptosis.

Stromal interaction molecule 1 (STIM1) is an endoplasmic reticulum Ca2+ sensor which has been reported to be overexpressed in numerous types of cancer, and is involved in the cell proliferation, invasion, migration and metastasis frequently observed in cancer. However, the role of STIM1 in colorectal cancer (CRC) remains unknown. The purpose of the present study was to investigate the effect of STIM1 in human CRC. The expression of STIM1 was specifically knocked down using lentivirus-mediated small hairpin RNA (shRNA) interference techniques in the CRC cell lines HCT116 and SW1116. Subsequently, the efficiency of infection was confirmed using green fluorescent protein (GFP)-positive signals. The knockdown efficiency was further determined using the reverse transcription-quantitative polymerase chain reaction and western blotting analysis. As a result, CRC cell lines with STIM1 silenced were successfully constructed and subsequently employed in a series of cell function assays. Knockdown of STIM1 significantly suppressed cell proliferation and colony formation, as revealed by an MTT and colony formation assay. Furthermore, it was identified that STIM1 silencing may promote cell apoptosis through the induction of mitochondria-associated apoptosis, as was identified by increased expression levels of B-cell lymphoma 2 (Bcl-2)-associated death promoter, Bcl-2-associated X protein and poly(ADP-ribose) polymerase cleavage. Therefore, STIM1 may serve a critical role in the progression of CRC by regulating cell proliferation and apoptosis, which may provide a potential therapeutic target for the treatment of CRC.