Upregulated β-galactoside α2,6-sialyltransferase I (ST6Gal-I) expression reportedly occurs in many cancers and is correlated with metastasis and poor prognosis. However, the mechanisms by which ST6Gal‑I facilitates gastric cancer progression remain poorly understood. Trastuzumab is exclusively used in human epidermal growth factor receptor 2 (HER2)+ gastric cancers; however, most advanced HER2+ gastric cancers develop trastuzumab resistance. Herein, we identified HER2 as an ST6Gal‑I substrate and showed that HER2 α2,6 sialylation confers protection against trastuzumab‑mediated apoptosis. SGC7901 cancer cell models in which ST6Gal‑I was overexpressed or knocked down were constructed, revealing that ST6Gal‑I overexpression induced high HER2 sialylation levels and increased cell viability and invasion compared to those in the vector cell line under serum starvation; ST6Gal‑I knockdown had the opposite effects. ST6Gal‑I overexpression also potentiated cell cycle arrest in the G2/S phase to reduce drug sensitivity. In addition, FACS analysis revealed that high ST6Gal‑I levels increased resistance to trastuzumab‑induced apoptosis, accompanied by decreased caspase‑3 levels. However, the ST6Gal‑I knockdown cell line revealed increased caspase‑3 levels and evident apoptosis compared with those in the vector cell line. Although ST6Gal‑I overexpression increased HER2 sialylation, corresponding to decreased HER2 phosphorylation, high α2,6‑sialylation enhanced Akt and ERK phosphorylation levels compared to those in the vector cell line; ST6Gal‑I knockdown had the opposite effects. Collectively, these results implicated a functional role of ST6Gal‑I in promoting tumor cell progression and trastuzumab resistance.

Background:Circulating cell-free DNA (cfDNA) isolated from plasma or serum by noninvasive procedures can serve as a “liquid biopsy” and has potential as a biomarker for the tumor burden and survival prediction of breast cancer (BC). However, its prognostic value in patients with BC is currently under debate. The aim of this meta-analysis was to investigate the relationship between cfDNA and survival outcome.Methods:We systematically searched PubMed, Embase, and Science Citation Index electronic databases for studies about the prognostic utility of cfDNA in patients with BC. The clinical characteristics, relapse/disease-free survival (RFS/DFS), and overall survival (OS) data were extracted from the eligible studies. The hazard ratios (HR) and 95% confidence intervals (CI) were calculated and pooled with a fixed-effects model using the Stata12.0 software. Subgroup and sensitivity analyses were also performed.Results:This meta-analysis included a total of 10 eligible studies and 1127 patients with BC. The pooled HR with 95% CI showed strong associations between cfDNA and OS (HR = 2.41, 95% CI, 1.83–3.16) along with DFS/RFS (HR = 2.73, 95% CI, 2.04–3.67) in patients with BC. Although publication bias was found in the studies regarding RFS/DFS, further trim and fill analysis revealed that the adjusted HR would be 2.53 (95% CI, 1.83–3.51), which is close to the original HR. Subgroup analyses confirmed the role of cfDNA as a strong prognostic marker in patients with BC, regardless of cfDNA analysis, sampling time, sample source, detection method, tumor stage, sample size, or area.Conclusions:Our meta-analysis indicates that cfDNA is a strong predictive and prognostic marker in patients with BC.

Background: Gene therapy is considered a novel way to treat osteosarcoma, and microRNAs are potential therapeutic targets for osteosarcoma. miR-214 has been found to promote osteosarcoma aggression and metastasis. Graphene oxide (GO) is widely used for gene delivery for the distinct physiochemical properties and minimal cytotoxicity. Methods: Polyethyleneimine (PEI)-functionalized GO complex was well-prepared and loaded with miR-214 inhibitor at different concentrations. The load efficacy was tested by gel retardation assay and the cy3-labeled fluorescence of cellular uptake. The experiments of wound healing, immunofluorescence staining, Western blot, qRT-PCR and immunohistochemical staining were performed to measure the inhibitory effect of the miR-214 inhibitor systematically released from the complexes against MG63, U2OS cells and xenograft tumors. Results: The systematic mechanistic elucidation of the efficient delivery of the miR-214 inhibitor by GO-PEI indicated that the inhibition of cellular miR-214 caused a decrease in osteosarcoma cell invasion and migration and an increase in apoptosis by targeting phosphatase and tensin homolog (PTEN). The synergistic combination of the GO-PEI-miR-214 inhibitor and CDDP chemotherapy showed significant cell death. In a xenograft mouse model, the GO-PEI-miR-214 inhibitor significantly inhibited tumor volume growth. Conclusion: This study indicates the potential of functionalized GO-PEI as a vehicle for miRNA inhibitor delivery to treat osteosarcoma with low toxicity and miR-214 can be a good target for osteosarcoma therapy.

Background: The overall survival (OS) among patients with advanced breast cancer (ABC) varies greatly.Although molecular subtype is known as the most important factor in OS differentiation, significant differences in OS among patients with the same molecular subtype still occur, leading to the need for a more accurate prognostic prediction model. This study aimed to develop a prediction model (nomogram) based on current diagnosis and treatment to predict the OS of newly diagnosed ABC patients in China.Methods: From the institution's database, we collected data of 368 ABC patients from Sun Yat-sen Memorial Hospital (national hospital) as a training set to establish a nomogram with prognostic risk factors that calculated the predicted probability of survival. Nomograms were independently validated with 278 patients with ABC from two other institutions using the concordance index (C-index), calibration plots and risk group stratifications. Results:The initial primary tumor stage, molecular subtype, disease-free survival (DFS), presence of brain metastasis, and the tumor burden of metastasis disease (local recurrence, oligo-metastatic disease, or multiple-metastatic disease) were included in the prognostic nomogram. The nomogram had a C-index of 0.77 and 0.71 in the training and the validation sets, respectively. The nomogram was able to stratify patients into different risk groups, respectively (HR 6.81, 95% CI: 4.69 to 9.89, P<0.001). In the lower risk score group (risk score <11), there was no significant difference between the OS with chemotherapy and hormone therapy (HR 0.81, 95% CI: 0.44 to 1.47, P=0.48). Conclusions:We have constructed a novel prediction nomogram that can guide the physicians to select personalized treatment options. Furthermore, our study is the first to add oligo-metastatic disease and primary endocrine/trastuzumab resistance into the prognostic models.

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