Activation of Glycolysis by MCM10 Increases Stemness and Paclitaxel Resistance in Gastric Cancer Cells.

BACKGROUND/AIMS: Chemotherapy is an essential avenue for curing malignancies; however, tumor cells acquire resistance to chemotherapeutic agents, eventually leading to chemotherapy failure. At present, paclitaxel (PTX) resistance seriously hinders the therapeutic efficacy of gastric cancer (GC). Investigating the molecular mechanism of PTX resistance in GC is critical. This study attempted to delineate the impact of MCM10 on GC resistance to PTX and its mechanism in GC. MATERIALS AND METHODS: The expression of minichromosome maintenance complex component 10 (MCM10) in GC tissues, its enrichment pathways, and its correlation with glycolysis marker genes and stemness index (mRNAsi) were analyzed in a bioinformatics effort. Real-time quantitative polymerase chain reaction was used to assay the expression of MCM10 in cells. Cell counting kit-8 (CCK-8) was used to analyze cell viability and calculate the 50% inhibitor concentration (IC50) value. Western blot was used to measure the expression of MCM10, Hexokinase 2 (HK2) and stemness-related factors in cells. Sphere-forming assay was performed to study cell sphere-forming ability. Seahorse XF 96 was utilized to measure cell extracellular acidification and oxygen consumption rates. The content of glycolysisrelated products was tested with corresponding kits. RESULTS: MCM10 was significantly upregulated in GC and enriched in the glycolysis pathway, and it was positively correlated with both glycolysis-related genes and stemness index. High expression of MCM10 increased sphere-forming ability of drug-resistant cells and GC resistance to PTX. The stimulation of PTX resistance and drug-resistant cell stemness in GC by high MCM10 expression was mediated by the glycolysis pathway. CONCLUSION: MCM10 was upregulated in GC and drove stemness and PTX resistance in GC cells by activating glycolysis. These findings generated new insights into the development of PTX resistance in GC, implicating that targeting MCM10 may be a novel approach to improve GC sensitivity to PTX chemotherapy.

Identification of Biomarkers Associated with the Prognoses of Colorectal Cancer Patients.

INTRODUCTION: Colorectal cancer (CRC) is a common cancer. As metastasis and recurrence are main causes of CRC death, it is of great significance to find prognostic biomarkers. METHODS: Data related to CRC were collected from GEO database. The patients were grouped based on clinical information, and the differentially expressed genes (DEGs) were obtained by differential analysis. GO and KEGG pathway enrichment analyses were conducted based on DEGs. Cox combined with LASSO regression analysis was applied to screen out the key genes that used to build the prognostic model. Survival curve and receiver operating characteristic curve were employed to evaluate the validity and reliability of the model. Cox regression analysis was applied to determine the independence of risk score. GSEA and GSVA analyses were performed on patients with different risks according to the risk model scores, and the prognostic nomogram was plotted combined with clinical data. Also, qRT-PCR was applied to examine the expression status of the screened signatures in clinical cases. RESULTS: We obtained 302 DEGs by dividing CRC patients into early-stage and advanced-stage groups. The results of enrichment analyses demonstrated that the DEGs were mainly concentrated in tissues of extracellular matrix, epithelial cell proliferation, and cell adhesion-related pathways. Regression identified 9 hub genes notably correlated with prognosis, including CLK1, SLC2A3, LIPG, EPHB2, ATOH1, PLCB4, GZMB, CKMT2, and CXCL11. The validation of the risk model proved that the risk model was accurate and could independently determine the prognosis of patients. Finally, differences were found in pathway activity of extracellular matrix secretion, plaque secretion, Notch signaling pathway, and tight junctions in high-risk and low-risk patients. In addition to LIPG and CKMT2, other feature genes were notably overexpressed in CRC tumor tissues. CONCLUSION: The results proved that the expression levels of the 9 biomarkers could be used to predict the prognosis of CRC patients.

Primary ascending colon cancer accompanying skip metastases in left shoulder skin and left neck lymph node: A case report.

BACKGROUND: Lymph node skip metastases are common in lung, breast, and thyroid cancer patients, but are rare in colon cancer patients. Specifically, lymph node skip metastases occur in 1%-3% of colon cancer patients. Previous reports have demonstrated colon cancer skip metastases involving the retropancreatic and portocaval lymph nodes and Virchow's node; however, reports involving skip metastases into the left neck lymph nodes and left shoulder skin are extremely rare, as are related reports of clinical treatment and prognosis. CASE SUMMARY: A 44-year-old Chinese man was admitted to the hospital for evaluation of persistent shoulder pain for 3 d and a cutaneous mass (3.0 cm × 2.0 cm) on the left shoulder. The left shoulder cutaneous mass was excised and bisected, revealing tissues with a fish-like appearance. The pathologic diagnosis of the cutaneous mass suggested a signature [CDX-2 (++), CK20 (++), Ki-67 (+) > 50%] of infiltrating or metastatic colorectal adenocarcinoma. An enhanced computed tomography scan of the abdomen revealed chronic appendicitis with fecal stone formation, cecal edema, and a pelvic effusion. A colonoscopy revealed a cauliflower-like mass within the ascending colon area that involved the lumen. The surface of the ascending colon mass was eroded and bleeding; a biopsy was performed. The pathologic diagnosis of the colonoscopy biopsy was an ascending colon mucinous adenocarcinoma. The patient underwent a laparoscopic radical resection of the right colon based on the pathological diagnosis. The tumor was 5.0 cm × 4.5 cm × 1.8 cm in size and infiltrated the entire thickness of the intestinal wall with vascular tumor thrombi. No nerve tissue involvement was noted. The ileum and colon resection margins were negative. The postoperative pathologic analysis revealed non-metastatic involvement of ileocecal, pericolic, or peri-ileal lymph nodes. The postoperative medical examination revealed palpably enlarged lymph nodes in the left neck, and the following color Doppler ultrasound examination of the neck confirmed enlarged lymph nodes in the left neck. After surgical resection and pathologic diagnosis, a common pathologic signature consistent with resected cutaneous mass and right colon was identified, suggesting skip metastasis of left cervical lymph nodes. The patient was then treated with eight courses of chemotherapy and under follow-up evaluations for 4 years; currently, no tumor recurrences or metastases have been noted. CONCLUSION: We report an abnormal skip metastasis involving the left shoulder skin and left neck lymph node in a patient with ascending colon adenocarcinoma. Specifically, we observed non-metastatic involvement of the lymph nodes around the tumor site but with metastases to the cervical lymph nodes. The standard surgical operations were performed to resect the cutaneous mass, tumor tissue, and cervical lymph nodes, followed by chemotherapy for eight courses. The patient is healthy with no tumor recurrences or metastases for 4 years. This clinical case will contribute to future research about the abnormal skip metastasis in colon cancers and a better clinical treatment design.

MiR-194-3p modulates the progression of colorectal cancer by targeting KLK10.

BACKGROUND: A rich history of studies have manifested the importance of miRNAs to cancer progression, while miR-194-3p has been seldom explored. OBJECTIVE: The purpose of this study is to unearth the way the KLK10/miR-194-3p axis modulates colorectal cancer (CRC). METHODS: Differentially expressed genes of CRC in TCGA database were analyzed. Western blot and qRT-PCR were employed to test protein and mRNA expressions of two researched genes. Their targeting was confirmed using dual-luciferase. Biological behaviors of cells were tested by a series of cellular functional assays. RESULT: Remarkably low miR-194-3p expression and high KLK10 expression were observed in cancer cells. Overexpressing miR-194-3p hindered the progression of CRC cells. Overexpression of miR-194-3p significantly weakened the promoting effect of upregulated KLK10 on cell migration, invasion and proliferation. Their targeting was verified by dual -luciferase assay. Therefore, miR-194-3p hindered cell behaviors of CRC through KLK10. CONCLUSION: This investigation casts new light on the treatment of CRC through the KLK10/miR-194-3p axis.

Research for Expression and Prognostic Value of GABRD in Colon Cancer and Coexpressed Gene Network Construction Based on Data Mining.

Colon cancer is one of the top five cancers with the highest incidence rate in the world. In order to better understand the pathogenesis and progression of colon cancer, it is still necessary to investigate the abnormally expressed genes in cancer tissue. In this study, the Oncomine database was used for expression analysis, and it was found that the expression level of gamma-aminobutyric acid type A receptor subunit delta (GABRD) gene was upregulated in colon cancer tissue compared with that in normal tissue. UALCAN was used to analyze the expression of GABRD in different groups of age, gender, cancer stage, N stage, and histological subtype. Then, it was also found that the expression of GABRD in each subgroup of colon cancer tissue was all high compared with that in normal tissue. LinkedOmics was used to screen out the differentially expressed genes related to GABRD expression in colon cancer. GO annotation and KEGG pathway enrichment analyses found that the correlated genes may be related to breast cancer, human papillomavirus infection, Notch signaling pathway, and other pathways. Thereafter, GSEA was performed to obtain GABRD-related kinases, miRNAs, and transcription factors, and gene interaction networks were constructed. It was found that GABRD may be involved in cell cycle regulation. Finally, websites like GEPIA were used to detect the predictive ability of GABRD on the prognosis of patients with colon cancer. Kaplan-Meier analysis suggested that the upregulation of GABRD expression was related to the poor prognosis of patients with colon cancer. Overall, in this study, the potential role and prognostic ability of GABRD in colon cancer were explored through data mining, which can be a clue for further research on GABRD.

TRIM32 Promotes the Growth of Gastric Cancer Cells through Enhancing AKT Activity and Glucose Transportation.

Tripartite motif protein 32 (TRIM32), an E3 ubiquitin ligase, is a member of the TRIM protein family. However, the underlying function of TRIM32 in gastric cancer (GC) remains unclear. Here, we aimed to explore the function of TRIM32 in GC cells. TRIM32 was induced silencing and overexpression using RNA interference (RNAi) and lentiviral-mediate vector in GC cells, respectively. Moreover, the PI3K/AKT inhibitor LY294002 was used to examine the relationship between TRIM32 and AKT. Quantitative reverse-transcription PCR (qRT-PCR) and western blot were used to determine the mRNA and protein contents. The glucose analog 2-NBDG was used as a fluorescent probe for determining the activity of glucose transport. An annexin V-fluorescein isothiocyanate apoptosis detection kit was used to stain NCI-N87, MKN74, and MKN45 cells. Cell counting kit-8 (CCK-8) assay was used to examine cell proliferation. Our results indicated that TRIM32 was associated with poor overall survival of patients with GC. Moreover, TRIM32 was a proproliferation and antiapoptosis factor and involved in the AKT pathway in GC cells. Furthermore, TRIM32 possibly mediated the metabolism of glycolysis through targeting GLUT1 and HKII in GC cells. Importantly, TRIM32 silencing deeply suppressed the tumorigenicity of GC cells in vivo. Our findings not only enhanced the understanding of the function of TRIM32 but also indicated its potential value as a target in GC treatment.

Clinical outcomes of laparoscopic versus open right hepatectomy for liver tumors: A meta-analysis.

BACKGROUND: Laparoscopic right hepatectomy (LRH) is one of the most challenging procedures. Right liver resections have been always performed in open procedure and open right hepatectomy (ORH) was initially considered as routine way. Moreover, it is unclear how beneficial the minimally invasive technique is to patients; thus, we conducted a meta-analysis to acquire a more reliable conclusion about the feasibility and safety of LRH compared with ORH. METHODS: We comprehensively searched the electronic databases of PubMed, Embase, and the Cochrane Library using the key words. Meta-analysis was performed using the Review Manager, with results expressed as odds ratio and weighted mean difference with 95% confidence intervals. The fixed-effect model was selected initially if high heterogeneity was not present between the studies; otherwise, the randomized-effect model was used. Subgroup analysis was performed based on different surgical methods of pure laparoscopic operation or hand-assisted operation. RESULTS: Seven studies with 467 patients were included. In the overall analysis, less intraoperative blood loss (MD = -155.17; 95% CI, -238.89, -71.45; P = .0003) and a shorter length of stay (MD = -4.45; 95% CI, -5.84, -3.07; P < .00001) were observed in the LRH group compared to the ORH group. There were fewer overall complications (OR = 0.30; 95% CI, 0.10, 0.90; P = 0.03) and severe complications (OR = 0.24; 95% CI, 0.10, 0.58; P = .002;) in the LRH group than in the ORH group. The disadvantage of LRH was the longer operative time (MD = 49.39; 95% CI, 5.33, 93.45; P = .03). No significant difference was observed between the 2 groups in portal occlusion, rate of R0 resection, transfusion rate, mild complications, and postoperative mortality. In the subgroup analysis, intraoperative blood loss was significantly lower in the pure LRH group and hand-assist LRH group compared with ORH group. Length of stay was shorter by use of pure LRH and hand-assisted LRH manners than ORH. The incidence rate of complications was lower in the pure LRH group than in the ORH group. In contrast, there was no significant difference between hand-assisted LRH group and ORH group. CONCLUSION: Compared to ORH, LRH has short-term surgical advantages and leads to a shorter recovery time in selected patients. We speculate that the operative time of LRH is closer with ORH. Overall, LRH can be considered a feasible choice in routine clinical practice with experienced surgeons, although more evidence is needed to make a definitive conclusion.

[Application of three-dimensional laparoscopy in radical gastric cancer surgery].

OBJECTIVE: To explore the application of three-dimensional (3D) high-definition (HD) laparoscopy in radical operation for stomach carcinoma. METHODS: A total of 12 cases of radical operation for stomach carcinoma were performed under 3D laparoscopy. The procedures included total gastrectomy (n = 6) and distal gastrectomy (n = 6). The operative duration, intraoperative blood loss, number of lymph node harvested, postoperative first flatus day and time of food intake were recorded and analyzed. RESULTS: All cases were successfully operated without complications. The operative duration was 180-210 min, blood loss 50-150 ml, number of lymph node harvested 32-54 and postoperative first faltus day 1-3 days. Also all cases could take fluids at Days 4-5 postoperation. CONCLUSION: 3D laparoscopic radical operation for gastric cancer may be performed safely and effectively with decreased surgical difficulties.

Downregulated expression of metastasis associated in colon cancer 1 (MACC1) reduces gallbladder cancer cell proliferation and invasion.

Metastasis associated in colon cancer 1 (MACC1), a key regulator of the hepatocyte growth factor (HGF)/MET signaling pathway, has been implicated in multiple human cancers. However, little is known regarding its expression and biological function in human gallbladder cancer (GBC). In this study, we focused on the clinical significance and biological functions of MACC1 in GBC and found that MACC1 protein overexpression was frequently detected in GBC tissues. Patients with MACC1-positive tumors had worse overall survival than patients with MACC1-negative tumors. Furthermore, treatment of GBC lines with MACC1-targeting small interfering RNA oligonucleotides (MACC1-siRNA) significantly reduced the proliferation of GBC-SD and OCUG-1 cell lines and diminished both anchorage-independent growth on soft agar and cell migration. These data indicate that MACC1 acts as a putative oncogene in GBC and could be a novel diagnostic and therapeutic target for GBC.

[Significance of MACC1 protein expression in esophageal carcinoma].

OBJECTIVE: To explore the expression of metastasis-associated colon cancer 1 (MACC1) proteins in esophageal carcinoma and neighboring tissues. METHODS: The expressions of MACC1 were detected in 60 specimens of esophageal carcinoma and neighboring tissues with immunohistochemistry and Western blotting. All the specimens were selected from 2010-2012 of Guangfu Hospital of Jinhua, 38 males and 22 females, aged (50 ± 12) years. And the correlations of the expressions of MACC1 proteins with the clinicopathologic features of esophageal carcinoma were also analyzed. RESULTS: Expression of MACC1 protein was predominantly located in cytoplasm and membrane. The positivity rates of MACC1 protein were 68.3% (41/60) in esophageal carcinoma tissue and there were significant differences from those in neighboring tissue (25.0(15/60), P < 0.01). Western blotting analysis showed that the expression level of MACC1 protein in esophageal carcinoma was greater than that in corresponding adjacent tissues (0.64 ± 0.05 vs 0.21 ± 0.10, P < 0.05). Moreover, the positivity rates and relative expressions of MACC1 showed significant correlations with TNM stage and pathology grade (all P < 0.05). CONCLUSION: The abnormal expression of MACC1 may be associated with malignant progression of esophageal carcinoma.