ELAPOR1 suppresses tumor progression in colorectal cancer and indicates favorable prognosis.

BACKGROUND: The role of ELAPOR1 has been evaluated in several cancers but has not been elucidated in colorectal cancer (CRC). OBJECTIVE: To investigate the role of ELAPOR1 in CRC. METHODS: In the present study, the correlation between ELAPOR1 and survival of CRC patients in TCGA-COAD-READ datasets was predicted, and the difference in ELAPOR1 expression between tumor and normal tissues was analyzed. ELAPOR1 expression in CRC tissues was measured by immunohistochemistry. Then, ELAPOR1 and ELAPOR1-shRNA plasmids were constructed and transfected into SW620 and RKO cells. The effects were assessed by CCK-8, colony formation, transwell, and wound healing assays. Transcriptome sequencing and bioinformatics analysis were performed on the genes before and after ELAPOR1 overexpression in SW620 cells; the differentially expressed genes were substantiated by real-time quantitative reverse transcription PCR. RESULTS: High level of ELAPOR1 is associated with favorable disease-free survival and overall survival. Compared to normal mucosa, ELAPOR1 is lower in CRC. Moreover, ELAPOR1 overexpression significantly inhibits cell proliferation and invasion in vitro in SW260 and RKO cells. Conversely, ELAPOR1-shRNA promotes CRC cell proliferation and invasion. Among the 355 differentially expressed mRNAs identified, 234 were upregulated and 121 were downregulated. Bioinformatics indicated that these genes are involved in receptor binding, plasma membrane, negative regulation of cell proliferation, as well as common cancer signaling pathways. CONCLUSIONS: ELAPOR1 plays an inhibitory role in CRC and may be used as a prognostic indicator and a potential target for treatment.

GUSBP11 Inhibited The Progression of Triple Negative Breast Cancer via Targeting The miR-579-3p/SPNS2 Axis.

Objective: Growing evidences have exposed the important roles of long noncoding RNAs (lncRNAs) in the triple negative breast cancer (TNBC) inhibition. The function of glucuronidase beta pseudogene 11 (GUSBP11) in the TNBC occurrence remains obscure. To detect the function of GUSBP11 in TNBC progression and explore its downstream molecular mechanism. Materials and Methods: In this experimental study, using quantitative reverse transcription real-time polymerase chain reaction (RT-qPCR), we measured the GUSBP11 expression in the TNBC cell lines. Gain-of-function assays, including colony formation, flow cytometry, and western blot were used to identify the probable effects of GUSBP11 overexpression on the malignant behaviors of TNBC cell lines. Moreover, mechanism assays, including RNA immunoprecipitation (RIP), RNA pull down and luciferase reporter assays were taken to measure the possible mechanism of GUSBP11 in the TNBC cell lines. Results: GUSBP11 expressed at a low RNA level in the TNBC cell lines. Overexpression of GUSBP11 RNA expression inhibited the proliferation, migration, epithelial-to-mesenchymal transition (EMT) and stemness while elevated the apoptosis of the TNBC cell lines. GUSBP11 positively regulated the expression of sphingolipid transporter 2 (SPNS2) via acting as a competing endogenous RNA (ceRNA) of miR-579-3p, thereby suppressing the development of TNBC cell lines. Conclusion: GUSBP11 impedes TNBC progression via modulating the miR-579-3p/SPNS2 axis.

Preoperative Hepatic and Regional Arterial Chemotherapy in Patients Who Underwent Curative Colorectal Cancer Resection: A Prospective, Multi-center, Randomized Controlled Trial.

OBJECTIVE: To evaluate the effects of the addition of preoperative hepatic and regional arterial chemotherapy (PHRAC) on prognosis of stage II and III colorectal cancer (CRC) in a multicenter setting. SUMMARY OF BACKGROUND DATA: Our previous single-center pilot trial suggested that PHRAC in combination with surgical resection could reduce the occurrence of liver metastasis (LM) and improve survival in CRC patients. METHODS: A prospective multi-center randomized controlled trial was conducted from December 2008 to December 2012 at 5 hospitals in China. Eligible patients with clinical stage II or III CRC who underwent curative resection were randomized to receive PHRAC plus adjuvant therapy (PHRAC arm) or adjuvant therapy alone (control arm). The primary endpoint was DFS. Secondary endpoints were cumulative LM rates, overall survival (OS), and safety (NCT00643877). RESULTS: A total of 688 patients from 5 centers in China were randomly assigned (1:1) to each arm. The five-year DFS rate was 77% in the PHRAC arm and 65% in the control arm (HR = 0.61, 95% CI 0.46-0.81; P = 0.001). The 5-year LM rates were 7% and 16% in the PHRAC and control arms, respectively (HR = 0.37, 95% CI 0.22-0.63; P < 0.001). The 5-year OS rate was 84% in the PHRAC arm and 76% in the control arm (HR = 0.61, 95% CI 0.43-0.86; P = 0.005). There were no significant differences regarding treatment related morbidity or mortality between the two arms. CONCLUSIONS: The addition of PHRAC could improve DFS in patients with stage II and III CRC. It reduced the incidence of LM and improved OS without compromising patient safety. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00643877.

RANBP9 suppresses tumor proliferation in colorectal cancer.

RAN binding protein 9 (RANBP9) is widely expressed in mammalian tissues, including osteosarcoma, lung, gastric and breast cancer tissues. However, currently, not much is known about the role of RANBP9 in colorectal cancer (CRC). In the present study, RANBP9 expression in CRC tissues and cell lines was measured by immunohistochemistry and western blotting, respectively. Subsequently, RANBP9-short hairpin RNA (shRNA) and RANBP9 plasmids were constructed and transfected into HCT116 and HT29 cells. The effects of RANBP9 knockdown were assessed by Cell Counting kit-8 and colony formation assays, and its effects on tumorigenicity in a nude mouse animal model were investigated. The effect of RANBP9-shRNA on cell cycle progression was analyzed by flow cytometry, while cell cycle-associated protein expression levels were examined by western blotting. Compared with in paired normal mucosa, RANBP9 was overexpressed in CRC tissues. Inhibition of RANBP9 in HCT116 and HT29 cells significantly promoted cell growth, colony formation and S phase transition, and increased tumorigenesis in vivo. Accordingly, RANBP9 overexpression inhibited cell growth and colony formation. Knockdown of RANBP9 was associated with upregulated cyclin A2 in the two cell lines. In conclusion, RANBP9 served an inhibitory role in CRC in vitro and in vivo. Therefore, RANBP9 may be considered a potential target for treatment of CRC.

Reduced RANBP9 expression is associated with poor prognosis in colorectal cancer patients.

BACKGROUND: Colorectal cancer (CRC) is the third most common malignancy worldwide. RANBP9 is a RAN-binding protein that has been reported to be a reliable predictor for prognosis in some human cancers. The mechanism of RANBP9 involvement in CRC carcinogenesis is unknown. This study measured RANBP9 expression levels in CRC to determine its association with clinicopathological parameters. METHODS: This study included 228 CRC patients who underwent radical resection. RANBP9 expression was determined using immunohistochemistry. Based on follow-up data, the correlation of RANBP9 expression levels with clinicopathological parameters, including disease free survival (DFS) and overall survival (OS) was evaluated. RESULTS: Reduced RANBP9 expression was correlated with tumor location (P=0.014), vascular invasion (P=0.057) and normal serum carcinoembryonic antigen levels (P=0.001). Patients with reduced RANBP9 expression had a 5-year DFS rate of 63.0% compared to 78.9% for patients with high expression levels of RANBP9 (P=0.015). Subgroup analysis demonstrated that reduced RANBP9 expression was significantly correlated with a worse DFS rate (P=0.037) for patients with left-sided colon cancer. RANBP9 was found to be an independent predictive factor for estimating DFS rate (P=0.029, hazard ratio: 0.580, 95% confidence interval: 0.356-0.946) and OS. CONCLUSIONS: RANBP9 expression levels is a potential prognostic factor for estimating CRC survival rates in patients after surgery.

CDKL1 promotes tumor proliferation and invasion in colorectal cancer.

BACKGROUND: CDKL1 is a member of the cell division cycle 2 (CDC2)-related serine threonine protein kinase family and is overexpressed in malignant tumors such as melanoma, breast cancer, and gastric cancer. OBJECTIVE: This study aimed to evaluate whether CDKL1 can serve as a potential molecular target for colorectal cancer therapy. MATERIALS AND METHODS: Expression of CDKL1 in colorectal cancer tissues and cell lines was measured by immunohistochemistry and Western blot, respectively. To investigate the role of CDKL1 in colorectal cancer, CDKL1-small hairpin RNA-expressing lentivirus was constructed and infected into HCT116 and Caco2 cells. The effects of RNA interference (RNAi)-mediated CDKL1 downregulation on cell proliferation and invasion were assessed by CCK-8, colony formation, transwell, and tumorigenicity assays in nude mice. The effects of CDKL1 downregulation on cell cycle and apoptosis were analyzed by flow cytometry. Furthermore, microarray method and data analysis elucidated the molecular mechanisms underlying the phenomenon. RESULTS: CDKL1 protein was overexpressed in colorectal cancer tissues compared with paired normal tissues. Knockdown of CDKL1 in HCT116 and Caco2 significantly inhibited cell growth, colony formation ability, tumor invasion, and G1-S phase transition of the cell cycle. The knockdown of CDKL1 stimulated the upregulation of p15 and retinoblastoma protein. CONCLUSION: CDKL1 plays a vital role in tumor proliferation and invasion in colorectal cancer in vitro and in vivo and, thus, may be considered as a valuable target for therapeutic intervention.

Randomized Controlled Trial of Intraportal Chemotherapy Combined With Adjuvant Chemotherapy (mFOLFOX6) for Stage II and III Colon Cancer.

OBJECTIVES: The optimal time to initiate adjuvant chemotherapy after surgery in patients with colon cancer is not clear. We investigated the benefit of combined intraportal chemotherapy administered during radical surgery with adjuvant chemotherapy for treating stage II and III colon cancer. METHODS: Patients were randomly assigned to OCTREE arm (intraportal chemotherapy plus mFOLFOX6) or a standard adjuvant chemotherapy arm (mFOLFOX6). The primary study endpoint was disease-free survival. The secondary endpoints included metastasis-free survival, overall survival, and safety. RESULTS: The intent-to-treat population comprised 237 patients. With a median follow-up of 44 months, the hazard ratio (OCTREE vs mFOLFOX6) was 0.66 (95% confidence interval, 0.43-0.90), a 34% risk reduction in favor of OCTREE (P = 0.016). The 3-year disease-free survival rate was 85.2% for OCTREE and 75.6% for mFOLFOX6 alone (P = 0.030). The 3-year metastasis-free survival rates were 87.6% for OCTREE and 78.0% for mFOLFOX6 (P = 0.035). Patients had lower distant metastatic rate in the OCTREE arm (12.7% vs 22.7%; P = 0.044), when compared with the mFOLFOX6 arm. The 3-year overall survival was no significant difference between 2 arms (P = 0.178). Neutropenia occurred in 12.7% of the patients receiving OCTREE and in 2.5% of the patients receiving mFOLFOX6 (P = 0.003) within 2 weeks of surgery, and grade 3 or 4 toxicity event was no difference between 2 regimens. CONCLUSIONS: Combination of intraoperative intraportal chemotherapy with mFOLFOX6 reduced the occurrence of distant metastases and improved disease-free survival in patients with stage II and stage III colon cancer.

Tumor deposit is a poor prognostic indicator in patients who underwent simultaneous resection for synchronous colorectal liver metastases.

BACKGROUND: Tumor deposits are one of the important influencing factors among the different editions of Tumor, Node, Metastasis classification. Incidence and prognosis of tumor deposits in stage I, II, and III colorectal cancer patients has been explored. The aim of this study was to determine the prognostic value of tumor deposits in stage IV colorectal cancer patients who underwent simultaneous resection for synchronous colorectal liver metastases (SCRLM). METHODS: Clinicopathological and outcome data of 146 consecutive SCRLM patients who underwent simultaneous R0 resection between July 2003 and July 2013 were collected from our prospectively established SCRLM database. The prognostic value of tumor deposits was evaluated by Kaplan-Meier and Cox regression analysis. RESULTS: Tumor deposits were detected in 41.8% (61/146) of these SCRLM patients. Tumor deposits were significantly correlated with lymph node metastasis and nerve invasion of the primary tumors (P=0.002, P=0.041; respectively). The Kaplan-Meier survival analysis revealed that the overall survival (OS) and disease-free survival (DFS) of SCRLM patients with tumor deposits were significantly poorer than those with no tumor deposits (P=0.039, P=0.001; respectively). And with multivariate analysis, we found that positive tumor deposits were significantly associated with shorter DFS independent of lymph node status (P=0.002). Subgroup analysis found that of the 57 SCRLM patients with negative lymph node status, the OS and DFS of patients with positive tumor deposits were significantly shorter than those with negative tumor deposits (P=0.002 and P=0.031, respectively). Of the 89 patients with positive lymph node status, the OS of patients with tumor deposits was not significantly different than those without tumor deposits (P=0.965); however, the DFS of patients with tumor deposits was significantly shorter than those with no tumor deposits (P=0.034). CONCLUSION: Tumor deposits may be an independent adverse prognostic factor in SCRLM patients who underwent simultaneous R0 resection.