Survival and clinicopathological significance of blood vessel invasion in operable breast cancer: a systematic review and meta-analysis.

BACKGROUND: Lymphovascular invasion, including lymphatic-vessel invasion and blood-vessel invasion, plays an important role in distant metastases. The metastatic pattern of blood-vessel invasion may differ from that of lymphatic-vessel invasion. However, its prognostic significance in breast cancer remains controversial. We evaluated the role of blood-vessel invasion in the prognosis of operable breast-cancer patients and its association with clinicopathological characteristics. METHODS: We systematically searched EMBASE, PubMed, the Cochrane Library and Web of Science for studies in English through December 2020. Disease-free survival, overall survival and cancer-specific survival were the primary outcomes. Pooled hazard ratios and 95% confidence intervals were assessed using a random-effects model. RESULTS: Twenty-seven studies involving 7954 patients were included. Blood-vessel invasion occurred in 20.4% of tumor samples. Pooled results showed significant associations of blood-vessel invasion with worse disease-free survival (hazard ratio = 1.82; 95% confidence interval = 1.43-2.31) and overall survival (hazard ratio = 1.86; 95% confidence interval = 1.16-2.99) in multivariate analyses. The results of the univariate analyses were similar. Among the clinicopathological factors, blood-vessel invasion was associated with larger tumor size, lymph-node metastasis, nonspecific invasive type, higher histological grade, estrogen receptor-negative breast cancer, human epidermal growth factor receptor 2-positive breast cancer and lymphatic-vessel invasion. In the lymph-node-negative subgroup analyses, the presence of blood-vessel invasion led to poorer disease-free survival (hazard ratio = 2.46; 95%confidence interval = 1.64-3.70) and overall survival (hazard ratio = 2.94; 95%confidence interval = 1.80-4.80). CONCLUSIONS: We concluded that blood-vessel invasion is an independent predictor of poor prognosis in operable breast cancer and is associated with aggressive clinicopathological features. Breast-cancer patients with blood-vessel invasion require more aggressive treatments after surgery.

Circulating CD8+ T-cell repertoires reveal the biological characteristics of tumors and clinical responses to chemotherapy in breast cancer patients.

PURPOSE: CD8+ T cells are primarily cytotoxic cells that provide immunological protection against malignant cells. Considerable evidence suggests that the T-cell repertoire is closely associated with the host immune response and the development of cancer. In this study, we explored the characteristics of the circulating CD8+ T-cell repertoire and their potential value in predicting the clinical response of breast cancer patients to chemotherapy. EXPERIMENTAL DESIGN: We applied a high-throughput TCR ß-chain sequencing method to characterize the CD8+ T-cell repertoire of the peripheral blood from 26 breast cancer patients. In addition, changes in the circulating CD8+ T-cell repertoire during chemotherapy were analyzed. RESULTS: We found that the HEC ratios of the CD8+ T-cell repertoires from HER2+ breast cancer patients were significantly higher than those of HER2- patients, suggesting that the HER2 protein is released into circulation where it is targeted by CD8+ T cells. Several Vß and CDR3 motifs preferentially used in HER2+ patients were identified. Besides, we found that the circulating CD8+ T-cell repertoires evolved during chemotherapy and correlated with patient clinical responses to chemotherapy. Increased CD8+ T-cell repertoire heterogeneity during chemotherapy was associated with a better clinical response. CONCLUSIONS: Although functional studies of clonally expanded CD8+ T-cell populations are clearly required, our results suggest that the circulating CD8+ T-cell repertoire reflects the characteristics of the tumor-associated biomolecules released into the blood and correlates with the clinical responses of the patients to chemotherapy which might assist in making treatment decisions.

Comparison of regulatory networks of E74-like factor 1 and cold-shock domain-containing E1 in breast cancer cell lines using ChIP datasets.

In the present study, differences in the expression of target genes between chromatin immunoprecipitation sequencing (ChIP-seq) datasets of breast cancer MCF-7 cells treated with antibodies to E74-like factor 1 (ELF1) and cold-shock domain-containing E1 (CSDE1) were analyzed and gene regulatory networks were established. The datasets were downloaded from the Gene Expression Omnibus (GEO) database. ELF1-associated target genes and CSDE1-associated target genes were analyzed for functional prediction and protein-protein interaction (PPI) networks. The ELF1 ChIP-seq dataset contained 95 ELF1-associated target genes, while the CSDE1 ChIP-seq dataset contained 826 CSDE1-associated target genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the ELF1- and CSDE1-associated target genes had different potential functions and signaling pathways. The ELF1-associated target genes were mainly enriched in the GO terms of molecular transducer activity, catalytic activity, cellular processes and response to sensitivity, and in the KEGG pathways of olfactory transduction, the chemokine signaling pathway, carbohydrate digestion and absorption, and starch and sucrose metabolism. The CSDE1-associated target genes were mainly enriched in the GO terms of binding, transcription regulator activity, cellular processes and metabolic processes, and in the KEGG pathways of ribosome, metabolic pathways, endocytosis, oxidative phosphorylation and transcriptional misregulation in cancer. PPI network analysis revealed that the ELF1 regulatory network primarily regulated chemokine-mediated malignant tumor cells, while the CSDE1 regulatory network mainly regulated ribosomes, metabolic pathways and oxidative phosphorylation. Reverse transcription-quantitative PCR indicated that ELF1 overexpression led to significant downregulation of C-X-C motif chemokine-8 and -6 expression levels in MCF-7 cells, while overexpression of CSDE1 significantly induced the mRNA expression of CSDE1-associated target genes, which included mitochondrial ribosomal protein L4, NADH: ubiquinone oxidoreductase subunit B7, small nuclear ribonucleoprotein polypeptide E, ribosomal protein S26 (RPS26), RPS11 and RPS6, in the MCF-7 cells. In breast cancer MCF-7 cells, the target genes and regulatory pathways of ELF1 and CSDE1 were different. Understanding these regulatory pathways may help to develop strategies for personalized breast cancer treatment.

The novel long non­coding RNA PRNCR1­2 is involved in breast cancer cell proliferation, migration, invasion and cell cycle progression.

Long non­coding RNAs (lncRNAs) have recently been reported to act as important mediators of tumor initiation and progression. The present study aimed to investigate the expression and pathogenic roles of the lncRNA prostate cancer­associated non­coding RNA (PRNCR)1­2 in breast cancer. The expression levels of PRNCR1­2 were detected in breast cancer tissues and numerous breast cancer cell lines using reverse transcription­quantitative polymerase chain reaction. Depletion of PRNCR1­2 expression in breast cancer cells was conducted through small interfering RNA­mediated silencing. Subsequently, cell proliferation was assessed by MTS assay, cell migration and invasion capacities were evaluated using the Transwell culture system, and cell cycle progression and apoptosis were analyzed by flow cytometry. Protein expression levels of the signaling components checkpoint kinase 2 (CHK2), protein kinase B (AKT), phosphorylated (p)­CHK2 and p­AKT were measured by western blotting. The results demonstrated that PRNCR1­2 expression was significantly elevated in breast cancer tissues compared with in adjacent normal tissues. Furthermore, depletion of PRNCR1­2 in HS­578T and MDA­MB­231 breast cancer cells markedly suppressed their proliferation rates, migration and invasion capacities, and cell cycle progression; however, it had no effect on cell apoptosis. In addition, PRNCR1­2 depletion increased CHK2 phosphorylation and decreased AKT phosphorylation in HS­578T and MDA­MB­231 cells. In conclusion, the lncRNA PRNCR1­2 may promote breast cancer cell proliferation, migration, invasion and cell cycle progression.

[Clinical analysis of 33 cases of primary esophageal small cell carcinoma].

BACKGROUND & OBJECTIVE: Esophagus is the most commonly involved site of extrapulmonary small cell carcinoma. However, no standard treatment has been established for primary esophageal small cell carcinoma. This study was to summarize the clinical characteristics, treatment, and prognosis of primary esophageal small cell carcinoma, and explore the impact of chemotherapy on the survival. METHODS: The records of 33 patients with primary esophageal small cell carcinoma, treated in Cancer Center of Sun Yat-sen University from Jan. 1985 to Dec. 2005, were reviewed to summarize the clinical characteristics and impact of therapy modality on the survival. Prognostic factors were analyzed by Kaplan-Meier and log-rank method. RESULTS: The median survival time of the 33 patients was 11.3 months; the 1-, 3-, and 5-year survival rates were 45.1%, 16.6%, and 3.5%, respectively. Clinical stage was the most important prognostic factor. The median survival time of the patients received local treatment (surgical operation or radiotherapy) was 6.3 months; the 1-, 2-, 3-year survival rates were 31.1%, 23.5%, and 8.2%, respectively. The median survival time of the patients received local treatment plus chemotherapy was 15.4 months; the 1-, 2-, 3-year survival rates were 69.3%, 34.6%, and 28.7%, respectively. CONCLUSION: Surgical operation plus chemotherapy can improve the survival of the patients with early stage primary esophageal small cell carcinoma.