Identification of hub genes in AR-induced tamoxifen resistance in breast cancer based on weighted gene co-expression network analysis.

BACKGROUND: Approximately 30% of patients with oestrogen receptor (ER)-positive breast cancer (BC) exhibit intrinsic or recurrent resistance to tamoxifen (TAM) adjuvant endocrine therapy. The androgen receptor (AR) is expressed in about 90% of ER-positive patients. Our previous studies found that BC patients with an AR:ER expression ratio ≥ 2.0 are more susceptible to TAM resistance. However, the specific mechanism by which a high AR:ER ratio promotes TAM resistance remains unknown. METHODS: RNA sequencing was performed on 10 cases of BC tissues with AR:ER ratios ≥ 2.0 and 3 cases with AR:ER ratios < 2.0. We then compared our data with the screened TAM-resistant and TAM-sensitive cases from the TCGA BC database. Bioinformatics methods were used to screen differentially expressed genes (DEGs) and to perform gene enrichment analysis. Weighted correlation network analysis (WGCNA) was used to screen hub genes in the AR-induced TAM resistance process. RESULTS: PAM50 analysis showed that the molecular phenotype of BC patients with AR:ER ratios ≥ 2.0 was similar to that of triple-negative breast cancer (TNBC), whereas the BC samples with AR:ER ratios < 2.0 were classified as the luminal subtype. Among the AR:ER ratio ≥ 2.0 and AR:ER < 2.0 BC tumours, 1855 DEGs were identified. Gene enrichment analysis showed that DEGs were enriched mainly in proliferation-related molecular pathways, such as the cell cycle, necroptosis, metabolic pathways and DNA replication. WGCNA analysis showed that SEC14L2, RIIAD1, STC2 and MAGEA6 served as hub genes in AR-induced TAM resistance and were associated with BC survival prognosis in the TCGA cohort. CONCLUSIONS: A high AR:ER expression ratio is a biomarker for patients who might develop TAM resistance, and AR expression seems to be a possible mechanism of resistance to endocrine therapy.

Endoreplication and its role in tumor development and progression / 中国肿瘤临床

Most diploid cells proliferate by proceeding through the canonical G1 (DNA pre-synthesis), S (DNA synthesis), G2 (DNA post-synthesis), and M(mitosis) phases of the cell cycle. However, there is another type of cell cycle that occurs frequently in both plants and animals, known as endoreplication. Endoreplication consists of alternating periods of G and S phases without cytokinesis, which results in polyploidy. It is indispensable for normal development, organ formation, and wound healing in humans. In recent years, con-siderable attention has been paid to delineating the connections of endoreplication with tumorigenesis and tumor progression. Here, we review the role of endoreplication in normal human development and discuss its possible role in tumor development and the un-derlying molecular mechanisms.

Dickkopf-1 inhibits vasculogenic mimicry formation of colon can-cer and relevant mechanism / 中国肿瘤临床

Objective:To investigate the inhibitory effect of Dickkopf-1 (Dkk1) on vasculogenic mimicry (VM) formation and the relevant mechanism. Methods:CD34-PAS dual staining and immunohistochemical staining were used to detect and analyze the re-lationship between VM existence and Dkk1 expression in 217 human colon cancer tissue samples;three dimensional (3D) culture was used to detect the influence of Dkk1 on tube structure formation and on VE-cadherin expression;a subcutaneous mouse xenograft mod-el was made to further validate the inhibitory role of Dkk1 on VM formation in vivo. Results:VM-positive samples indicated a lower expression of Dkk1(P<0.05);colon cancer cells with Dkk1 overexpression exhibited a decreased ability to form tube-like structure and a decreased expression of VE-cadherin;Dkk1 inhibited the VM-formation abilities of human colorectal carcinoma cell line xenograft tu-mor tissue. Conclusion:Dkk1 inhibits the VM formation of colon cancer.

Mechanism and research advances regarding adaption of nutrition insufficiency for tumor cells / 中国肿瘤临床

Given the unlimited proliferation and aerobic glycolysis in tumor cells, these cells require more glucose, glutamine, and other nutrients compared with normal cells. Tumor cells are often affected by insufficient nutrient supply. However, by sensing changes in the nutrient supply in tumor microenvironment and by regulating signal-transduction pathways, some specific proteins can help tumor cells in blocking the cell cycle, reprogramming metabolism, and regulating autophagy to progress and survive against nutri-ent stress. Exciting innovations have been made to elucidate the mechanisms relevant to this process. This review aims to highlight re-cent studies on the mechanisms of sensing the low nutrient supply in microenvironments, as well as the downstream effect factors in cancer cells.

Renal and extra-renal rhabdoid tumor:analysis of 4 cases and lit-erature review / 中国肿瘤临床

Objective:To analyze the clinico-pathological characteristics, pathological diagnosis, and treatment of rhabdoid tu-mor. Methods:The medical records of four rhabdoid tumor patients that were admitted to the Tianjin Medical University Cancer Insti-tute and Hospital since 2000 were analyzed based on existing literature. Results:In one of the four cases, the tumor originated from the kidney, whereas in the other three, the tumor occurred from extra-renal soft tissues. Histologic analysis revealed that the tumor cells were loosely arranged with diffuse growth, vesicular nuclei, dyed cytoplasm, visible eosinophilic inclusions, and more nuclear fission. The results of immunohistochemical staining showed that the vimentin and epithelial membrane antigen were positive, whereas CK, CD99, CD34, and S-100 were positive at different degrees. MyoD1, Desmin, and INI-1 were negative. Conclusion:Rhabdoid tumor is rare and highly aggressive. It occurs mainly in the kidney and can also be found in other systems. The unique pathological form and im-munohistochemical staining observed on the tumor can be used as reference for diagnosis.

Research of colon cancer stem cell-like cells induced to differenti-ate into vascular endothelial cells / 中国肿瘤临床

Objective:This study aims to investigate the potential of colon cancer cells to differentiate into vascular endothelial cells in endothelial-induced specific environment. Methods:Three colon cancer cells with different differentiated level HCT116 (poor-ly differentiated), SW480 (moderately differentiated), HT29 (well differentiated) were cultured in the conditioned medium containing the endothelial-inducing factors for 15 days respectively. The expression of vascular endothelial indicators Platelet endothelial cell adhe-sion molecule-1、Endothelial cell adhesion molecule CD34 was detected via western blot. Immunofluorescence staining was performed to examine CD31 and CD34 expression level in HCT116 after cultured in endothelial-inducing medium and ordinary medium for 15 days respectively, and the three-dimensional (3D) culture was used to detect the abililty of in vitro tube-like structure formation. Re-sults:Western blot showed that CD31 and CD34 expression level were negatively correlated with degree of differentiation in colon can-cer cells. CD31 and CD34 expression in endothelial-inducing medium HCT116 cells (poorly differentiated) were higher then in the nor-mal medium, while the CD31 and CD34 expression in SW480 cells (moderately differentiated) and HT29 cells (well differentiated) in the two cultural mediums were not notably changed. Immunofluorescence staining illustrated that CD31 and CD34 expression in HCT116 cells cultured in endothelial-inducing medium increased compared with those cultured in ordinary medium. In vitro three-di-mensional culture demonstrated that ability of tube-like structure formation was notably enhanced after endothelial-inducing cultured. Conclusion:Endothelial-inducing medium could promote colon cancer cells with strong stemness differentiate toward vascular endo-thelial cells.