The efficient circulating immunoscore predicts prognosis of patients with advanced gastrointestinal cancer.

BACKGROUND: Immunoscore from tumor tissues was initially established to evaluate the prognosis of solid tumor patients. However, the feasibility of circulating immune score (cIS) for the prognosis of advanced gastrointestinal cancers (AGC) has not been reported. MATERIAL AND METHODS: Peripheral venous blood was collected from 64 untreated AGC patients. We utilized flow cytometry to determine several immune cell subpopulations, including CD8+ and CD4+ T cells, NK cells, and CD4 + CD25 + CD127low Tregs. The circulating immune score 1 (cIS1) was assessed according to the proportions of CD4+, CD8+ T cells, and NK cell, whereas circulating immune score 2 (cIS2) was derived from the proportions of CD4+, CD8+ T cell, and CD4 + CD25 + CD127low Tregs. The prognostic role of cIS for progression-free survival (PFS) and overall survival (OS) was analyzed using Kaplan-Meier curves and Cox multivariate models. Receiver operating characteristic (ROC) curves were depicted to compare the prognostic values of cIS1 and cIS2. RESULTS: AGC patients with high cIS1(≥ 2) and cIS2(≥ 2) had significantly longer PFS (cIS1: median PFS, 11 vs. 6.7 months, P = 0.001; cIS2: 12 vs. 5.8 months, P < 0.0001) and OS (cIS1: median OS, 12 vs. 7.9 months, P = 0.0004; cIS2: 12.8 vs. 7.4 months, P < 0.0001) than those with low cIS1 and low cIS2. The areas under ROC curves (AUROCs) of cIS1 and cIS2 for OS were 0.526 (95% confidence interval; 95% CI 0.326-0.726) and 0.603 (95% CI 0.427-0.779, P = 0.332), whereas AUROC of cIS2 for PFS was larger than that of cIS1 0.735 (95% CI 0.609-0.837) vs 0.625 (95% CI 0.495-0.743) (P = 0.04)). CONCLUSION: The cIS can be applied to predict the prognosis of untreated AGC patients. Compared with cIS1, cIS2 displayed superior prognostic value for PFS prediction.

High expression of aldolase A is associated with tumor progression and poor prognosis in hepatocellular carcinoma.

BACKGROUND: Aldolase A (ALDOA), a key glycolytic enzyme, has been reported to play an important role in lung, pancreatic, and colorectal cancer. However, the role and mechanism of ALDOA in hepatocellular carcinoma (HCC) are still unclear. This study aimed to study the role and potential mechanism of ALDOA in HCC. METHODS: The changes in expression level and clinical implications of ALDOA in HCC were studied through bioinformatics and online databases. The prognostic role of ALDOA was investigated by Kaplan-Meier and Cox regression survival analysis. We explored the potential mechanism of ALDOA in the development of HCC by gene set enrichment analysis (GSEA). RESULTS: The expression level of ALDOA was significantly increased in HCC compared with adjacent normal tissues (P<0.001). The expression level of ALDOA was significantly associated with tumor, node, metastasis (TNM) stage, histologic grade, and p53 mutation (all P<0.05). Prognostically, HCC patients with high expression of ALDOA indicated poorer prognosis and shorter survival time. In addition, univariate and multivariate Cox regression analysis further suggested that overexpression of ALDOA was an independent prognostic risk factor (P<0.05). Furthermore, the nomogram was developed based on ALDOA expression and tumor TNM stage. Besides, ALDOA DNA copy gain and methylation were associated with ALDOA upregulation in HCC. Finally, GSEA suggested that high expression of ALDOA was associated with glucose catabolic process, cell cycle, DNA replication, E2F1 pathways, protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathways, and CD4 T cell related immune biological processes. CONCLUSIONS: There is a close relationship between ALDOA and HCC progression, and ALDOA may be a novel prognostic biomarker and a promising drug target for the treatment of HCC.

LncRNA MCM3AP-AS1 promotes breast cancer progression via modulating miR-28-5p/CENPF axis.

Breast cancer is one of the commonly occurred cancers among women and poses a huge threat against female health. Abnormal expression of lncRNA has been confirmed to be an important inducer of cancer. By searching GEO and TCGA database, we found that CENPF was upregulated in breast cancer tissues. Through RT-qPCR, CENPF was found to be upregulated in breast cancer cells. Functional experiments revealed that CENPF had positive effect on the cellular functions, including proliferation, migration and invasion. Subsequently, CENPF was confirmed to combine with miR-28-5p, and its expression was suppressed by miR-28-5p. Furthermore, it was found that miR-28-5p bound to MCM3AP-AS1, and MCM3AP-AS1 expressed at a high level in breast cancer cells. Besides, MCM3AP-AS1 was confirmed as a cytoplasmic RNA. In addition, there was a positive expression correlation between MCM3AP-AS1 and CENPF. Therefore, MCM3AP-AS1 was confirmed to regulate CENPF via competitively binding to miR-28-5p. At last, rescue assays demonstrated that knockdown of CENPF restored miR-28-5p repression-induced cellular processes in MCM3AP-AS1-silenced cells. In vivo assay revealed that MCM3AP-AS1 could hasten tumor growth in breast cancer by targeting CENPF. All results indicated that MCM3AP-AS1/miR-28-5p/CENPF axis accelerates breast cancer progression.

Post-TACE combination therapy of heparin and octreotide results in decreased tumor metastasis in extrahepatic tumorigenesis.

Primary hepatocarcinoma is the most common type of malignant tumor and a leading cause of cancer mortality. Standard treatment for patients with advanced primary hepatocarcinoma for whom surgery is not recommended includes transcatheter arterial chemoembolization (TACE). Within these patients 44% develop metastasis within 1 year. Thus, understanding the events underlying the recurrent tumors and developing therapies in conjunction with TACE would be of great benefit. Reducing tumor angiogenesis by combining the somatostatin analog octreotide with small doses of heparin is one approach in decreasing metastasis rates by targeting VEGF and heparinase, respectively. Given this, we investigated whether a heparin and octreotide combination treatment administered post-TACE would decrease the tumor metastasizing rate in primary hepatocarcinoma. A total of 147 patients diagnosed with primary hepatocarcinoma were admitted to the study and received 2-4 TACE treatments and were monitored for 1 year. Of these 84 received the heparin plus octreotide combination treatment and 63 did not (control group). All patients were monitored for adverse reactions, coagulation ability, and tumor metastasis. We found a significant decrease in the incidence of tumor metastasis in patients receiving the combination treatment post-TACE for up to 1 year with no significant toxic or adverse effects. Thus, we propose using the combination treatment of heparin and octreotide post-TACE in the treatment of recurrent tumorigenesis in primary hepatocarcinoma.