NXPH4 mediated by m5C contributes to the malignant characteristics of colorectal cancer via inhibiting HIF1A degradation.

OBJECTIVE: Colorectal cancer (CRC) is a form of malignancy that exhibits a comparatively elevated occurrence and fatality rate. Given the relatively slower progress in diagnostic and therapeutic approaches for CRC, there is a need to investigate more accurate and efficient biomarkers. METHODS: Core regulatory genes were screened using the TCGA database, and the expression of neurexophilin 4 (NXPH4) and its prognostic implications were validated using tissue microarray staining. The assessment of NXPH4 functions involved a range of experiments, including cellular, organoid, and murine models. Furthermore, a regulatory network between m5C, NXPH4, and HIF1A was established through several in vitro experiments. RESULTS: The overexpression of NXPH4 is associated with unfavorable prognoses in patients with CRC and hepatocellular carcinoma. Additionally, it facilitates the progression of malignant tumors both in laboratory settings and in living organisms of colorectal carcinoma. Our research also reveals that NXPH4 mRNA can avoid degradation through RNautophagy, relying on an m5C-dependent mechanism. Moreover, NXPH4 amplifies the HIF signaling pathway and stabilizes HIF1A by competitively binding to PHD4. CONCLUSIONS: NXPH4, regulated by m5C, promotes malignant tumor progression and regulates the HIF pathway. Consequently, targeting NXPH4 through molecular therapies could potentially serve as an efficacious therapeutic strategy for the management of CRC exhibiting elevated NXPH4 expression.

CircBIRC6 facilitates the malignant progression via miR-488/GRIN2D-mediated CAV1-autophagy signal axis in gastric cancer.

Circular RNAs (circRNAs) represent a novel class of non-coding RNAs that play significant roles in tumorigenesis and tumor progression. High-throughput sequencing of gastric cancer (GC) tissues has identified circRNA BIRC6 (circBIRC6) as a potential circRNA derived from the BIRC6 gene, exhibiting significant upregulation in GC tissues. The expression of circBIRC6 is notably elevated in GC patients. Functionally, it acts as a molecular sponge for miR-488, consequently upregulating GRIN2D expression and promoting GC proliferation, migration, and invasion. Moreover, overexpression of circBIRC6 leads to increased GRIN2D expression, which in turn enhances caveolin-1 (CAV1) expression, resulting in autophagy deficiency due to miR-488 sequestration. This cascade of events significantly influences tumorigenesis in vivo. Our findings collectively illustrate that the CircBIRC6-miR-488-GRIN2D axis fosters CAV1 expression in GC cells, thereby reducing autophagy levels. Both circBIRC6 and GRIN2D emerge as potential targets for treatment and independent prognostic factors for GC patients.

Lysosome-Related Genes and RNF19B as Prognostic Markers for Survival and Immunotherapy Efficacy in Hepatocellular Carcinoma.

INTRODUCTION: Hepatocellular carcinoma (HCC) poses a considerable worldwide health concern due to its associated high risk of death. The heterogeneity of HCC poses challenges in developing practical risk stratification tools and identifying prognostic markers for personalized targeted treatments. Recently, lysosomes were shown to be crucial contributors to numerous cellular activities, including tumor initiation and immune response regulation. We aimed to construct a reliable prognostic signature based on lysosome-related genes and determine its association with the immune microenvironment. METHODS: We comprehensively analyzed lysosome-related genes in HCC to investigate their influence on patient survival and the tumor immune microenvironment. A prognostic signature comprising 14 genes associated with lysosomes was created to estimate the survival outcomes of individuals with HCC. In addition, we verified the prognostic importance of Ring Finger Protein 19B (RNF19B) in patients with HCC through multiplex immunohistochemistry analysis. RESULTS: Our constructed lysosome-related prediction model could significantly discriminate between HCC patients with good and poor survival outcomes ( P < 0.05). We also found that elevated RNF19B expression was linked to unfavorable prognostic outcomes and showed a connection with specific clinicopathological characteristics. Moreover, it was observed that RNF19B could facilitate the transformation of macrophages into M2-polarized macrophages and showed a significant positive correlation with PD-1 and CTLA-4. DISCUSSION: In summary, our study proposes that the expression of lysosome-related genes is associated with the immune microenvironment, serving as a predictor for HCC patient survival. Meanwhile, RNF19B was identified as a novel prognostic marker for predicting overall survival and immunotherapy effects in patients with HCC.

Retraction: An MSN-PEG-IP drug delivery system and IL13Rα2 as targeted therapy for glioma.

Retraction of 'An MSN-PEG-IP drug delivery system and IL13Rα2 as targeted therapy for glioma' by Jinlong Shi et al., Nanoscale, 2017, 9, 8970-8981, https://doi.org/10.1039/C6NR08786H.

WSCD2 Expression: Its Relevance to Tumor-Infiltrating Immune Cells and Glioma Prognosis.

BACKGROUND: Patients with glioma have limited treatment options and experience poor prognoses. Therefore, it is urgently needed to explore new diagnostic and therapeutic targets. OBJECTIVE: This study aimed to investigate the relevance of WSC domain-containing 2 (WSCD2) expression to glioma, clinicopathological characteristics, tumor-infiltrating immune cells (TILs), and patient prognosis. METHODS: We analyzed WSCD2 mRNA expression in glioma tissues and patient survival using the Gene Expression Profiling Interactive Analysis database. Furthermore, the relationship between the expressions of WSCD2 mRNA and TILs in gliomas was evaluated utilizing the Tumor Immune Estimation Resource database. Lastly, we employed multiplex immunohistochemistry to detect the protein expressions of WSCD2 and TILs in glioma tissues. RESULTS: WSCD2 mRNA expression in glioma tissues was lower than that in tissues of benign brain disease. High WSCD2 mRNA expression was also significantly associated with a favorable outcome. Additionally, WSCD2 mRNA expression was correlated with TIL expression in glioma; however, no such relationship was detected between the protein expressions of WSCD2 and TILs in glioma tissues. Cox regression multivariate analysis and Kaplan-Meier survival analysis showed that WSCD2 expression in glioma tissues could be an independent prognostic factor. CONCLUSION: This study highlights the correlation between WSCD2 expression and TILs and demonstrates the prognostic significance of WSCD2 in glioma. Furthermore, our results suggest that WSCD2 may be a potential immunotherapy target in glioma.

Basic Transcription Factor 3 Like 4 Enhances Malignant Phenotypes through Modulating Tumor Cell Function and Immune Microenvironment in Glioma.

Recent investigations into the tumor microenvironment have provided insights into the limited response of glioma progression to immunotherapy. However, the specific involvement of basic transcription factor 3 like 4 (BTF3L4) in glioma progression and its correlation with immune cell infiltration remain areas of uncertainty that require further exploration. In the current study, BTF3L4 expression was delineated by using gene expression profiling/interactive analysis and multiplex-immunohistologic staining of tissue microarrays. The prognostic value of BTF3L4 was then assessed by using Cox regression models and Kaplan-Meier methods, and in vitro experiments were conducted to investigate how BTF3L4 protein affects the proliferation, migration, and invasion capabilities of glioma cells. Furthermore, the CIBERSORT and ESTIMATE methods were used to quantify immune cells that correlate to BTF3L4 expression, and multiplex-immunohistologic staining was applied to investigate its correlation with infiltrated immune cells in glioma tissues. These findings revealed higher BTF3L4 expression in glioma tissues compared with non-tumor brain tissues, which correlated with clinical characteristics and worse patient prognosis. Furthermore, the down-regulation of BTF3L4 protein in the glioma cell line had a detrimental effect on cell migration, invasion, and proliferation. In addition, the association between BTF3L4 and key immune molecules in glioma, particularly with the infiltration of CD66B+ neutrophils and programmed death ligand 1 expression, was identified. These results highlight the prognostic significance of BTF3L4 and propose BTF3L4 as a potential target for glioma immune therapy.

HDAC3 Inhibition Promotes Antitumor Immunity by Enhancing CXCL10-Mediated Chemotaxis and Recruiting of Immune Cells.

It is generally believed that histone deacetylase (HDAC) inhibitors, which represent a new class of anticancer agents, exert their antitumor activity by directly causing cell-cycle arrest and apoptosis of tumor cells. However, in this study, we demonstrated that class I HDAC inhibitors, such as Entinostat and Panobinostat, effectively suppressed tumor growth in immunocompetent but not immunodeficient mice. Further studies with Hdac1, 2, or 3 knockout tumor cells indicated that tumor-specific inactivation of HDAC3 suppressed tumor growth by activating antitumor immunity. Specifically, we found that HDAC3 could directly bind to promotor regions and inhibit the expression of CXCL9, 10, and 11 chemokines. Hdac3-deficient tumor cells expressed high levels of these chemokines, which suppressed tumor growth in immunocompetent mice by recruiting CXCR3+ T cells into the tumor microenvironment (TME). Furthermore, the inverse correlation between HDAC3 and CXCL10 expression in hepatocellular carcinoma tumor tissues also suggested HDAC3 might be involved in antitumor immune regulation and patient survival. Thus, our studies have illustrated that HDAC3 inhibition suppresses tumor growth by enhancing immune cell infiltration into the TME. This antitumor mechanism may be helpful in guiding HDAC3 inhibitor-based treatment.

KRTCAP2 as an immunological and prognostic biomarker of hepatocellular carcinoma.

Alterations in protein glycosylation affect tumor progression and immune responses in the tumor microenvironment. Keratinocyte-associated protein 2 (KRTCAP2) encodes the corresponding proteins involved in N-glycosylation. The clinical predictive significance and immune role of KRTCAP2 in hepatocellular carcinoma (HCC) largely remain elusive. Combining bioinformatics tools and multiplex immunohistochemistry analysis, we evaluated the KRTCAP2 expression in the HCC tumor microenvironment. The results showed that KRTCAP2 mRNA and protein expression were markedly increased in HCC tissues. Furthermore, high KRTCAP2 expression was an independent predictive factor of unfavorable prognosis in HCC. Moreover, high KRTCAP2 protein expression was associated with a lower proportion of CD8+ T cells and CD68+ macrophages in the stroma region. There was also a lower proportion of CD8+ T cells in the tumor region with high KRTCAP2 protein expression. Specifically, KRTCAP2 expression showed an inverse relationship with programmed cell death ligand-1 in HCC. Analysis of immunophenoscore showed that the low KRTCAP2 expression group had a stronger ability to predict response to immune checkpoint inhibitors. In conclusion, KRTCAP2 had a significant prognostic value for HCC and was correlated with the immune microenvironment. Our findings suggest that KRTCAP2 is a prognostic marker for HCC patients with potential clinical implications for predicting immunotherapeutic responsiveness.

Clinical and molecular profiling of EGFR-mutant lung adenocarcinomas transformation to small cell lung cancer during TKI treatment.

Introduction: Small cell lung cancer (SCLC) transformation serves as a significant mechanism of resistance to tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. To address this clinical challenge, we conducted a retrospective analysis at Zhejiang University School of Medicine, the First Affiliated Hospital, focusing on patients with EGFR sensitizing mutations. Methods: A total of 1012 cases were included in this retrospective analysis. The cohort primarily consisted of patients with EGFR sensitizing mutations. Biopsy-confirmed small cell transformation was observed in seven patients, accounting for 0.7% of the cases. All patients in this subset were initially diagnosed with stage IV adenocarcinoma (ADC), with four cases classified as poorly differentiated and three as moderately to poorly differentiated ADC. EGFR exon 19 deletions were identified in five of these cases. Next-generation sequencing (NGS) was performed on seven cases, revealing mutations in the tumor protein p53 (TP53) gene in four cases and loss of the retinoblastoma1 (RB1) gene in three cases. Results: The median duration from the initial diagnosis to small cell transformation was 35.9 months (interquartile range: 12.1-84 months). Following small cell transformation during EGFR inhibition, all patients received etoposide/platinum-based treatment, leading to a median progression-free survival (PFS) of 4.7 months (interquartile range: 2.7-10.1 months). Notably, most patients in this series had poorly differentiated adenocarcinomas at the outset. TP53 mutations and RB1 loss were common genetic alterations observed in patients with small cell transformation in this cohort. Discussion: The findings underscore the clinical significance of SCLC transformation as a resistance mechanism to EGFR TKIs in NSCLC with EGFR mutations. The observed genetic alterations, including TP53 mutations and RB1 loss, suggest potential associations with the transformation process and warrant further investigation. Understanding the genetic landscape and clinical outcomes in patients experiencing small cell transformation can contribute to improved strategies for managing resistance in EGFR-mutant NSCLC.

KLHDC8A Expression in Association with Macrophage Infiltration and Oxidative Stress Predicts Unfavorable Prognosis for Glioma.

Background: The tumor immune microenvironment (TME) is associated with cancer progression and immune escape. Although KLHDC8A has been reported in glioma in vitro, the expression and clinical significance of this gene in clinical samples are unknown. Methods: The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases were used to evaluate the mRNA expression level of KLHDC8A and its significance in the glioma TME. Tissue microarray-based multiple immunohistochemical staining was conducted to determine KLHDC8A protein levels and characterize the immune signature of tumor-infiltrating immune cells in gliomas. Results: Tumor cells and tumor-associated macrophages expressed KLHDC8A. The expression of KLHDC8A was higher in glioma tissues than in normal brain tissues and was associated with patient clinical characteristics. Gliomas exhibited a high abundance of macrophages, neutrophils, regulatory T cells, and the immune checkpoint PD-L1, as well as high KLHDC8A expression. Cox regression analysis showed that KLHDC8A+CD68+ macrophages and KLHDC8A predicted unfavorable survival in patients with glioma. Finally, protein-protein interaction network analysis showed that the KLHDC8A expression was associated with hypoxia and oxidative stress. Conclusions: KLHDC8A is a potential marker for the clinical diagnosis of glioma. The immune characteristics of macrophages play a crucial role in predicting patients with glioma, providing a new avenue for targeted glioma therapy.

SPTSSA Is a Prognostic Marker for Glioblastoma Associated with Tumor-Infiltrating Immune Cells and Oxidative Stress.

Background: SPTSSA encodes the small subunit A of serine palmitoyltransferase. It catalyzes the formation of sphingoid long-chain base backbone of sphingolipids. Its role in glioma prognosis and tumor-infiltrating immune cells remains unclear. Methods: We analyzed SPTSSA expression and association with clinical prognosis using GEPIA and CGGA database. Then, GSEA was performed to identify relevant biological functions of SPTSSA. The correlations between SPTSSA expression and tumor immune infiltrates were investigated using CIBERSORT and TIMER. Finally, IHC and IF were performed to confirm the value of prognosis and the correlation with immune infiltration. Results: SPTSSA expression was significantly upregulated in diffuse glioma compared to normal tissues and associated with poor survival in GEPIA and CGGA database. Then, we identified biological processes and signaling pathways associated with SPTSSA expression. The result showed that SPTSSA enriched in the GO term like oxidative stress. Finally, we showed that SPTSSA expression was significantly associated with tumor-infiltrating immune cells and overall survival via IHC. Conclusion: These findings suggest that SPTSSA expression might be used as a prognostic biomarker for glioma and potential target for novel glioma therapy.

Identifying immune cells-related phenotype to predict immunotherapy and clinical outcome in gastric cancer.

Background: The tumor microenvironment is mainly composed of tumor-infiltrating immune cells (TIICs), fibroblast, extracellular matrix, and secreted factors. TIICs are often associated with sensitivity to immunotherapy and the prognosis of multiple cancers, yet the predictive role of individual cells on tumor prognosis is limited. Methods: Based on single-sample gene set enrichment analysis, we combined three Gene Expression Omnibus (GEO) cohorts to build a TIIC model for risk stratification and prognosis prediction. The performance of the TIIC model was validated using our clinical cohort and the TCGA cohort. To assess the predictive power of the TIIC model for immunotherapy, we plotted the receiver operating characteristic curve with the IMvigor210 and GSE135222 cohorts. Results: Chemokines, tumor-infiltrating immune cells, and immunomodulators differed between the two TIIC groups. The TIIC model was vital for predicting the outcome of immunotherapy. In our clinical samples, we verified that the expression levels of PD-1 and PD-L1 were higher in the low TIIC score group than in the high TIIC score group, both in the tumor and stroma. Conclusions: Collectively, the TIIC model could provide a novel idea for immune cell targeting strategies in gastric cancer and predict the survival outcome of patients.

Comprehensive Analysis of RELL2 as a Potential Biomarker Associated with Tumor Immune Infiltrating Cells in a Pan-Cancer Analysis.

Background: Receptor expressed in lymphoid tissues-like 2 (RELL2), which is a member of RELT family, is closely associated with the plasma membrane and acts as a modulator for RELT signaling. Overexpression of RELL2 induces the activation of MAPK14/p38 cascade and apoptosis. However, whether RELL2 contributes to cancers remains unclear. Here, we examined its role in cancer patient prognosis and various tumors. Methods: We used several bioinformatics methods, specifically gene set enrichment analysis (GSEA), ScanNeo, and ESTIMATE, to analyze the CCLE dataset, GTEx dataset, and TCGA dataset. We investigated the possible association of RELL2 with the microsatellite instability (MSI) of various tumors, tumor mutational burden (TMB), immune checkpoint, immune neoantigens, immune microenvironment, and patient prognosis. Result: RELL2 is highly expressed in cancer compared with normal tissues. RELL2 expression is linked with worse progression-free interval and overall survival in numerous cancers. In most cancers, high RELL2 expression was related to a poor prognosis. RELL2 expression was significantly associated with the tumor microenvironment, MSI, and TMB. RELL2 expression is strongly associated with phenotypes that are of major clinical significance, particularly those associated with immune neoantigens and the expression profiles of immune checkpoint genes in pan-cancer. RELL2 expression strongly linked with the expressions of methyltransferases and DNA repair genes. It also significantly correlated with multiple signaling pathways through gene set enrichment analysis. Conclusion: RELL2 may be a prognostic biomarker in pan-cancer and may have an important function in tumorigenesis and progression.

SNORD1C maintains stemness and 5-FU resistance by activation of Wnt signaling pathway in colorectal cancer.

Small nucleolar RNAs (snoRNAs) are a class of non-coding RNAs that play indispensable roles in cancers, including colorectal cancer (CRC). However, the role of SNORD1C in CRC is unclear. In the current study, SNORD1C expression was measured in CRC tissues using quantitative real-time PCR. A series of in vivo and in vitro experiments were performed to examine the functional role of SNORD1C in CRC. Quantitative real-time PCR, western blotting, sphere formation assay, and chemotherapy resistance analysis were conducted to illustrate the SNORD1C molecular mechanism. SNORD1C was upregulated in CRC and that high SNORD1C expression was related to poor prognosis. After knocking down SNORD1C in CRC cell lines, cell proliferation, colony formation, cell migration, and invasion were alleviated, while apoptosis was increased. Transcriptional RNA-sequencing analysis revealed that following SNORD1C knockdown, ß-catenin was downregulated, as was the transcription factor TCF7, which inhibited the Wnt/ß-catenin pathway. Meanwhile, levels of the stem cell-related factors were reduced, diminishing cell stemness and tumorigenesis. Our findings suggest that SNORD1C functions via the Wnt/ß-catenin pathway to enhance cancer cell stemness in CRC and could be a predictive biomarker for the prognosis ad aggressiveness of this malignancy. Additionally, targeting SNORD1C may be a novel therapeutic strategy for CRC.

Kinase DYRK2 acts as a regulator of autophagy and an indicator of favorable prognosis in gastric carcinoma.

Gastric cancer (GC) is the third leading cause of cancer-related death worldwide; therefore, new and more specific molecules for GC are needed. Here, we found that dual specificity tyrosine phosphorylation regulated kinase 2 (DYRK2) may be a specific marker for GC. Immunohistochemistry (IHC) and statistical and bioinformatics analyses were conducted to detect DYRK2 expression in stomach tissues. The role of DYRK2 in GC was analyzed with a nude mouse model and CCK-8, wound healing and Transwell assays. Western blotting and immunofluorescence experiments were also performed to elucidate the relationship between DYRK2 expression and both epithelial-mesenchymal transition (EMT) and autophagy progression. We found that DYRK2 expression in GC tissues was lower than that in benign or normal tissues, and patients with high DYRK2 expression had a good prognosis. The in vitro results showed that DYRK2 expression inhibited the tumorigenic activities of GC, including proliferation, migration, and invasion. By analyzing the expression of EMT markers after altering DYRK2 expression, we observed that DYRK2 inhibits the occurrence of EMT. The nude mouse model revealed that DYRK2 inhibits tumor growth. Finally, we used Western blotting and immunofluorescence assays and found that DYRK2 promotes autophagy. Based on these data, DYRK2 may be a good reference indicator for the clinical diagnosis of GC.

GARP Correlates With Tumor-Infiltrating T-Cells and Predicts the Outcome of Gastric Cancer.

Accepting the crucial role of the immune microenvironment (TME) in tumor progression enables us to identify immunotherapeutic targets and develop new therapies. Glycoprotein A repetitions predominant (GARP) plays a vital part in maintaining regulatory T cell (Treg)-mediated immune tolerance. The impact of GARP in TME of gastric cancer is still worth exploring. We investigated public genomic datasets from The Cancer Genome Atlas and Gene Expression Omnibus to analyze the possible role of GARP and its relationship with TME of gastric cancer. Fluorescence-based multiplex immunohistochemistry and immunohistochemistry for T-cell immune signatures in a series of tissue microarrays were used to validate the value of GARP in the TME. We initially found that GARP expression was upregulated in gastric carcinoma cells, and diverse levels o3f immune cell infiltration and immune checkpoint expression were detected. Gene expression profiling revealed that GARP expression was related to the TME of gastric cancer. GARP upregulation was usually accompanied by increased FOXP3+ Treg and CD4+ T cell infiltration. In addition, GARP expression had positive relationships with CTLA-4 and PD-L1 expression in gastric cancer. Cox regression analysis and a nomogram highlighted that the probability of poor overall survival was predicted well by GARP or GARP+CD4+ T cell. Taken together, this research underlines the potential effect of GARP in regulating survival and tumor-infiltrating T-cells. In addition, the function of CD4+ T cell immune signatures in the prognosis can be clinically meaningful, thereby providing a new idea for the immunotherapeutic approach.

Isolation and characterization of a novel chicken astrovirus in China.

Chicken astrovirus (CAstV) is associated with kidney disease and visceral gout, runting and stunting syndrome, and white chick hatchery disease, causing economic losses to the poultry industry worldwide. In this study, 55.6% of 36 clinical samples from Guangdong province in China were positive for CAstV, but negative for other common enteric viruses, including avian nephritis virus, infectious bronchitis virus, fowl adenovirus Group I, Newcastle disease virus, chicken parvovirus, reovirus, and rotavirus by PCRs and RT-PCRs. A CAstV strain, named GD202013, was isolated from Guangdong province in south China, and was identified by CAstV RT-PCR. A whole genome sequence analysis demonstrated that GD202013 shares 76.0 to 88.1% identity with 24 reference strains in GenBank. Phylogenetic analysis, based on whole genome and capsid protein, showed that GD202013 is more closely related to 2 US strains (GA2011/US/2011 and 4175/US/2011) belonging to subgroup Bii. Recombination analysis indicated that GD202013 is a recombinant strain formed by 3 strains: a major parent strain CkP5/US/2016, and 2 minor parent strains (GA2011/US/2011 and G059/PL/2014). In addition, the chicken embryo infection experiment demonstrated that GD202013 causes hatchability reduction, growth depression, and death of embryos. Macroscopic and microscopic lesions in the liver, kidney and small intestine were observed in the dead-in-shell embryos. This is the first report of the novel CAstV infection in China.

EphA8 inhibits cell apoptosis via AKT signaling and is associated with poor prognosis in breast cancer.

Erythropoietin­producing hepatocellular receptors (Ephs) comprise the largest subfamily of receptor tyrosine kinases and have been reported to be involved in a variety of biological cellular processes, including tumorigenesis and cancer progression. The present study aimed to determine the expression levels and clinicopathological significance of EphA8 in breast cancer (BC) using immunohistochemistry analysis of tissue microarrays. The results of the present study revealed that EphA8 expression levels were upregulated in BC tissue and were associated with tumor size and TNM stage. In addition, upregulated expression levels of EphA8 were identified to be a poor prognostic biomarker for patients with BC. The knockdown of EphA8 expression using short hairpin RNA resulted in increased levels of apoptosis as well as decreased proliferation, migration and invasion of BC cells both in vivo and in vitro. The knockdown of EphA8 also decreased the phosphorylation of AKT, which was accompanied by downregulation of Bcl­2 expression levels and upregulation of p53, Caspase­3 and Bax expression levels. Moreover, knockdown of EphA8 expression increased the chemosensitivity of BC cells to paclitaxel. In conclusion, the results of the present study indicated that EphA8 may be a useful prognostic marker in BC and that knockdown of EphA8 may represent a novel strategy in adjuvant chemotherapy for the treatment of BC.