Bioinformatics analysis reveals the clinical significance of GIPC2/GPD1L for colorectal cancer using TCGA database.

Background: Colorectal cancer (CRC) causes 700,000 deaths annually and is the fourth deadliest cancer in the world after lung, liver, and stomach cancer. Since CRC is difficult to detect early and has a poor prognosis, it is critical to develop novel biomarkers for its diagnosis, prognosis, and treatment. Methods: The GIPC2 expression in colorectal cancer was examined by the TCGA database analysis, IHC from the human protein atlas and qRT-PCR tests. GO and KEGG enrichment analyses were performed for genes that were both correlated with the expression of GIPC2 and GPD1L. The receiver operating characteristic curve (ROC) analysis and Kaplan-Meier (KM) survival analysis were applied to analyze the prognostic value of GIPC2 and GPD1L for overall survival (OS) and progress free interval (PFI) of CRC patients. Results: We found that GIPC2 was low expressed in colorectal cancer and highly related with the CRC clinical-stage grade and TNM stage. Furthermore, GPD1L is correlated with GIPC2 via the correlation analysis in CRC and they were associated with several important cancer-related pathways. GIPC2 and GPD1L exhibited good diagnostic and prognostic predictive ability for patients with CRC. Conclusions: These results revealed new biomarkers in CRC, we proposed that the GIPC2/GPDL1 might be potential diagnostic and prognostic indicators for CRC, which provides a theoretical basis for our subsequent cellular and animal experiments, so as to reveal the occurrence and development mechanism of CRC more comprehensively.

Systemic Immune-Inflammation Index (SII) Can Be an Early Indicator for Predicting the Severity of Acute Pancreatitis: A Retrospective Study.

OBJECTIVE: Systemic immune-inflammation index (SII) is a new systemic inflammatory prognostic indicator associated with outcomes in patients with different tumors. Studies have shown an association between SII and many chronic/acute inflammatory diseases. This study aimed at exploring whether SII can be used as an effective parameter for predicting the severity of acute pancreatitis (AP). METHODS: A total of 101 acute pancreatitis patients were enrolled in this study (mild acute pancreatitis (MAP): n = 73 and severe acute pancreatitis (SAP): n = 28). Patient demographics and SII were analyzed using the chi-square test, Student's t-test, and Mann-Whitney U-test. A receiver operating characteristic curve was generated to test the potential of using neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and SII to predict AP's severity. Logistic regression analysis was performed to determine major risk factors. RESULTS: Patients with SII value ≥2207.53 had a higher probability of having SAP (sensitivity = 92.9%, specificity = 87.7%, and AUC = 0.920), and SII was a significantly better predictive value than PLR and NLR. Logistic regression analysis results showed SII could differentiate MAP from SAP as a major risk factor. CONCLUSION: This study has shown that SII is a potential indicator for predicting the severity of acute pancreatitis. The findings suggested that SII is more sensitive and specific than NLR and PLR in predicting the severity of acute pancreatitis.

Pentraxin-3 inhibits milky spots metastasis of gastric cancer by inhibiting M2 macrophage polarization.

Purpose: Recent studies have indicated that Pentraxin-3 (PTX3) is related to invasion, migration and metastasis of gastric cancer cells (GCCs). However, the function of PTX3 in stemness and tumor-associated macrophages (TAMs) polarization in GC has not yet been revealed. Here, we investigated the role of PTX3 in TAMs polarization and stemness in gastric cancer (GC), and further explored the effect of PTX3 on milky spot metastasis of gastric cancer. Methods: PTX3 expression in human gastric cancer tissues was examined with immunohistochemistry (IHC). The influence on stemness of gastric cancer cells was examined by sphere formation assay and western blot. qRT-PCR, IHC and flow cytometry were used to evaluate M1/M2 macrophage signatures. The effects of PTX3 on TAM polarization and milky spots were investigated in vitro and in vivo. The possible mechanism of PTX3 on targeted cytokines and pathway were analyzed by qRT-PCR and western blot. Results: We found that PTX3 was low expressed in gastric carcinoma tissues and associated with stemness and polarization of macrophages. The upregulation of PTX3 inhibited the stemness of GCCs. Furthermore, PTX3 suppressed the polarization of M2 macrophages in the milky spots in vivo and in vitro and inhibited the metastasis of GC into milky spots. PTX3 restrained the expression of interleukin-4 (IL-4) and IL-10 via the inhibition of phosphorylation of the c-Jun N-terminal protein kinase 1/2 (JNK1/2) in GCCs. Conclusion: These results revealed a novel mechanism of PTX3 in GC, which may participate in the development and metastasis of GC by affecting stemness and macrophage polarization. PTX3 should be considered as a crucial biomarker and may be potentially used in targeted therapy in GC progression.

The Role of KDM2B and EZH2 in Regulating the Stemness in Colorectal Cancer Through the PI3K/AKT Pathway.

Background: The incidence of colorectal cancer (CRC) has been increasing worldwide in recent years. Targeting cancer stem cells (CSCs) in CRC remains a difficult challenge. KDM2B and EZH2 play important role in the maintenance of CSCs' self-renewal capacity and tumorigenic ability; however, the biological functions of those genes in CRC remain unclear. In this study, we aimed to define the contribution of the expression of KDM2B in the features of CRC and establish the relationship between KDM2B and EZH2 in colorectal CSCs. Methods: The expression of KDM2B and EZH2 in the specimens of CRC and CRC cell lines were analyzed by immunohistochemistry, Western blot, and immunofluorescence. The underlying mechanisms of altered expressions of KDM2B and EZH2 and their impact on the biologic features of CRC and stemness in CRC were investigated. Results: The KDM2B gene was highly expressed in CRC tissues, and its overexpression positively correlated with tumor stages and tumor/node/metastasis (TNM) classification. The downregulation of KDM2B retarded cell proliferation, induced DNA damage, reduced spheroid formation, and decreased CRC stem cell markers: CD44, CD133, and ALDH-1. Moreover, the downregulation of KDM2B decreased the expression of EZH2 and both regulated cell migration, invasion, and stemness in the CRC cell line. Additionally, the interaction between KDM2B and EZH2 significantly increased the components of the PI3K/AKT pathway including AKT and PI3K. The high expression of KDM2B positively correlated with EZH2 in CRC tissues. Conclusion: This study shows that the downregulation of KDM2B and EZH2 can regulate CRC cell stemness, and their interaction may serve as a novel prognostic marker and therapeutic target for patients with CRC.

USP37 downregulation elevates the Chemical Sensitivity of Human Breast Cancer Cells to Adriamycin.

Background: The evolution of adriamycin (ADR) resistance in the treatment of breast cancer often leads to a poor prognosis in patients. Ubiquitin-specific peptidase 37 (USP37) has been recently identified as a modulator in regulating the stemness of breast cancer cells, but its underlying mechanism remains unclear. In this study, we investigated whether USP37 knockdown could hamper the chemical resistance of MCF-7 and MCF-7/ADR cells to adriamycin and elucidated the potential mechanism. Methods: Immunohistochemistry, western blotting, and RT-qPCR assays were performed to detect the USP37 expression in MCF-7 and MCF-7/ADR cells. The efficiency of USP37 knockdown in breast cancer cells was confirmed by western blotting and RT-qPCR assays. We also performed CCK-8 assay, flow cytometry, western blotting, and TUNEL assays to evaluate cell viability and apoptosis in breast cancer cells. In vivo study was performed to detect the tumorigenicity of MCF-7/ADR cells transfected with shScramble or shUSP37#1 under adriamycin treatment. Results: Bioinformatic analysis indicated that USP37 overexpression was positively correlated with adriamycin resistance. The expression levels of USP37 in both MCF-7 and MCF-7/ADR cells increased significantly with the exposure to adriamycin in a dose-dependent manner. It was verified by the observation that USP37 downregulation elevated the inhibitory effects of adriamycin on breast cancer cells, suppressed cell proliferation caused by cell cycle arrest in G1/S transition, as well as induced apoptosis. Furthermore, in vivo study showed that knockdown of USP37 expression also decreased tumorigenicity of MCF-7/ADR cells in mice. TUNEL assay and observation of cell morphology magnified USP37 knockdown synergized with Adriamycin could elevate the apoptosis of MCF-7 and MCF-7/ADR cells. Western blotting assay illustrated that the combination of USP37 knockdown with adriamycin treatment significantly upregulated the expression levels of cleaved caspase 3 and Bax, whereas the expression level of Bcl-2 was inhibited. Conclusion: Knockdown of USP37 gene expression can reverse the resistance of breast cancer cells to adriamycin, and down-regulating USP37 might be a valuable strategy against ADR resistance in breast cancer therapy.

Cytokine TNF-α promotes invasion and metastasis of gastric cancer by down-regulating Pentraxin3.

As a novel multifaceted player in cancer, Pentraxin3(PTX3) was recognized to be a possible factor related with tumor development. Recent researches have indicated that PTX3 is involved in immune response, inflammation, as well as cancer, and is greatly controlled by numerous cytokines. Tumor necrosis factor (TNF-α) is an imperative cytokine that demonstrates an extensive array of biological consequences in gastric cancer advancement. Here, we inspected the expression of PTX3 in gastric carcinoma tissues along with gastric cell lines and established that PTX3 was suggestively inferior in gastric cancer tissue and cells. The treatment of the gastric cell lines BGC-823 as well as SGC-7901 with rhTNF-α caused substantial decrease in the expression of PTX3. Furthermore, PTX3 controlled the capability of cell migration, invasion as well as epithelial-mesenchymal transition (EMT) in gastric cancer cell lines mediated by TNF-α. Additionally, PTX3 upregulation inhibited tumorigenicity in vivo and could be reversed by exogenous TNF-α. Conversely, overexpression of PTX3 inhibited progress both in vitro as well as in vivo in gastric cancer mediated by TNF-α. Further studies are necessary to demonstrate the mechanism of interaction between PTX3 and cytokines.

ITGA3 interacts with VASP to regulate stemness and epithelial-mesenchymal transition of breast cancer cells.

BACKGROUND: The interaction of integrin and extracellular matrix (ECM) has a profound implication on pathological conditions such as tumor growth and infiltration. Related reports have confirmed that integrin α3 (ITGA3) influences the development of bladder cancer, head and neck cancer, colorectal cancer and other cancers. However, the mechanism of ITGA3 in breast cancer is unknown. METHODS: The impact of ITGA3 on the biological features of breast cancer cells was explored using the Transwell and wound healing assays. In addition, its influence on stemness of breast cancer cells was examined with the sphere formation assay. The possible mechanism by which ITGA3 regulates breast cancer was explored using Western blot. The interaction between ITGA3 and VASP was determined by co-immunoprecipitation and immunofluorescence staining assays. RESULTS: Results show that downregulation of ITGA3 promotes breast cancer cell proliferation, apoptosis, invasion and migration. Indeed, suppression of ITGA3 negatively regulates the stemness of breast cancer cells and EMT process. Our findings indicate that ITGA3 interacts with VASP and regulates its expression, and knockdown of ITGA3 inhibits the activity of the PI3K-AKT axis. CONCLUSION: Our results show that ITGA3-VASP modulates breast cancer cell stemness, EMT and PI3K-AKT pathways. Therefore, ITGA3 might be a druggable target for clinical breast cancer management.

Efficacy of Celiac Branch Preservation in Billroth-â Reconstruction After Laparoscopy-Assisted Distal Gastrectomy.

BACKGROUND: The goal of the present retrospective study was to elucidate the efficacy of conserving the celiac branch (CB), which can reduce the adverse reactions of Billroth-Ⅰ (B-Ⅰ) restoration after the laparoscopy-assisted distal gastrectomy (LADG). METHODS: Two hundred thirty-three patients with gastric cancer underwent B-Ⅰ reconstruction after LADG with dissection 2 lymphadenectomy from July 2005 to July 2012 and were monitored for 5 y. The patients were separated into 2 groups: celiac branch preserved (P-CB) group (n = 98) and celiac branch resected (R-CB) group (n = 135). In addition to patient information, tumor features, and surgical details, short-term and long-term variables such as bowel condition, surgical complications, and endoscopy findings were evaluated. RESULTS: In short-term efficacy, the time of first flatus and liquid ingestion were slightly shorter in the P-CB group than in the R-CB group (3.84 ± 0.74 versus 4.38 ± 0.71, P = 0.0001; 5.04 ± 1.07 versus 5.67 ± 1.10, P = 0.0001). For long-term efficacy, the incidences of chronic diarrhea, gastroparesis, residual food, bile reflux, and reflux esophagitis were less in the P-CB group compare with the R-CB group (6.1% versus 22.2%, P = 0.001; 5.1% versus 17.8%, P = 0.004; 4.1% versus 17.8%, P = 0.004; 8.2% versus 17.8%, P = 0.036; 8.2% versus 17.8%, P = 0.036). Other parameters such as postoperative ileus and gallstones had a better efficacy trend in the P-CB group but did not suggestively vary among the groups. CONCLUSIONS: The CB has an imperative part in the gastrointestinal motility, and celiac preservation mainly exerts long-term efficacy in patients who underwent B-I surgery with LADG.

Reviewing the Management of Obstructive Left Colon Cancer: Assessing the Feasibility of the One-stage Resection and Anastomosis After Intraoperative Colonic Irrigation.

BACKGROUND: The management of obstructive left colon cancer (OLCC) remains debatable with the single-stage procedure of primary colonic anastomosis after cancer resection and on-table intracolonic lavage now being supported. PATIENTS AND METHODS: Patients with acute OLCC who were admitted between January 2008 and January 2015 were distributed into 5 different groups. Group ICI underwent emergency laparotomy for primary anastomosis following colonic resection and intraoperative colonic lavage; Group HP underwent emergency Hartmann's Procedure; Group CON consisted of patients treated by conservative management with subsequent elective open cancer resection; Group COL were colostomy patients; and Group INT consisted of patients who had interventional radiology followed by open elective colon cancer resection. The demographics of the patients and comorbidity, intraoperative data, and postoperative data were collected, with P < .05 as significant. RESULTS: There were 4 deaths in 138 cases (2.90%). There was only 1 patient who had anastomotic leakage (5.56%) in Group ICI, compared with none in Group HP and Group COL, 1 case in Group INT (7.69%), and 2 cases in Group CON (6.06%) (P > .05). Group INT and Group CON, when compared to the three surgical groups, Groups ICI, Group COL, and Group HP, individually, were statistically significant for the duration of surgery (P < .05). CONCLUSIONS: Primary anastomosis following colonic resection after irrigation can be safely performed in selected patients, with the necessary surgical expertise, with no increased risk in mortality, anastomotic leakage, and other postoperative complications.