IL-34 and its receptors as predictors of brain metastasis and prognosis in lung adenocarcinoma: Unveiling insights through bioinformatic and immunohistochemical investigations.

Background: Brain metastasis (BM) is a prevalent form of metastasis in lung adenocarcinoma (LUAD), necessitating investigations into the underlying mechanisms. Interleukin 34 (IL-34) and its receptors, macrophage colony-stimulating factor-1 receptor (CSF-IR), Syndecan-1 (SDC-1), and protein-tyrosine phosphatase zeta receptor (PTPRZ1), are known to play pivotal roles in the metastasis of malignant tumors, thereby holding promise as potential biomarkers for studying BM in LUAD. Methods: We performed immunohistochemistry to analyze the expression of IL-34, CSF-1R, SDC-1, and PTPRZ1 in 10 pairs of LUAD primary tissues and BMs, along with 96 unpaired primary tissues and 68 unpaired BMs. Subsequently, we evaluated the association between protein expression and the occurrence of BM. Furthermore, Kaplan-Meier survival curve analysis was conducted on both network and clinical data to explore the association between protein expression and patient prognosis and survival. Results: At the protein level, the expression of IL-34 and its receptors showed significant variation between paired primary tumors and BMs in 10 LUAD patients. The levels of IL-34, CSF-1R, and SDC-1 expression are typically elevated in brain metastatic lesions of LUAD compared to primary LUAD tumors. Furthermore, patients with high CSF-1R expression in primary LUAD are at a greater risk of developing brain metastases. High expression of IL-34 and CSF-1R in primary LUAD lesions indicated poor disease-free survival (DFS) and overall survival (OS), while high expression of SDC-1 indicated poor OS. Cox multivariate analysis further revealed that CSF-1R and IL-34+CSF-1R positivity independently affected LUAD OS. These findings were further substantiated in unpaired samples. Conclusions: Our results indicate significant alterations in the expression of IL-34 and its receptors, CSF-1R and SDC-1, between LUAD primary lesions and BMs, with increased expression observed in BMs. LUAD patients with positive CSF-1R expression in primary lesions exhibited a higher likelihood of developing BM, and high expression of IL-34, CSF-1R, and SDC-1 correlated with poor prognosis. These findings contribute novel insights towards identifying potential treatment or diagnostic targets for metastatic LUAD.

Sec61γ is a vital protein in the endoplasmic reticulum membrane promoting tumor metastasis and invasion in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most common malignant tumors worldwide. Finding effective prognostic markers and therapeutic targets is of great significance for controlling metastasis and invasion clinically. METHODS: The open copy-number aberrations and gene expression datasets were analysed, and the data of 102 LUAD patients was used for further validation. The cell proliferation, colony formation, migration, invasion assays and mice tumor models were used to detect the function of SEC61G. The epidermal growth factor receptor (EGFR) pathway was also detected to find the mechanism of Sec61γ. RESULTS: Based on the open datasets, we found that the high level of SEC61G mRNA may drive LUAD metastasis. Furthermore, the overexpression of Sec61γ protein was significantly associated with poor prognosis and greater tumor cell proliferation and metastasis. The SEC61G knockdown could inhibit the EGFR pathway, including STAT3, AKT and PI3K, which can be reversed by Sec61γ overexpression and epithelial growth factor (EGF) supplement. CONCLUSIONS: Sec61γ promoted the proliferation, metastasis, and invasion of LUAD through EGFR pathways. Sec61γ might be a potential target for the treatment of LUAD metastases.

PM2.5 Exposure Induces Lung Injury and Fibrosis by Regulating Ferroptosis via TGF-ß Signaling.

Background: Lung fibrosis is a severe lung disorder featured by chronic nonspecific inflammation of the interstitial lung and deposition of collagen, leading to lung dysfunction. It has been identified that ferroptosis is involved in the progression of lung injury. Particulate matter (PM2.5) is reported to be correlated with the incidence of pulmonary fibrosis. However, mechanisms underlying ferroptosis in PM2.5-related lung fibrosis is unclear. In this study, we aimed to explore the effect of PM2.5 on ferroptosis in lung fibrosis and the related molecular mechanisms. Methods: PM2.5-treated mouse model and cell model were established. Fibrosis and tissue damage were measured by Masson's trichrome staining and HE staining. Fibrosis biomarkers, such as α-SMA, collagen I, and collagen III, were examined by histological analysis. The ferroptosis phenotypes, including the levels of iron, Fe2+, MDA, and GSH, were measured by commercial kits. ROS generation was checked by DCFH-DA. The oxidative stress indicators, 3-nitro-L-tyrosine (3'-NT), 4-HNE, and protein carbonyl, were checked by enzyme linked immunosorbent assay (ELISA). The thiobarbituric acid reactive substances (TBARS) and GSH/GSSG ratio were assessed by TBARS assay kit and GSH/GSSG assay kit, respectively. TGF-ß signaling was detected by Western blotting. Results: PM2.5 induced the lung injury and fibrosis in the mice model, along with elevated expression of fibrosis markers. PM2.5 enhanced oxidative stress in the lung of the mice. The SOD2 expression was reduced, and NRF2 expression was enhanced in the mice by the treatment with PM2.5. PM2.5 triggered ferroptosis, manifested as suppressed expression of GPX4 and SLC7A11, decreased levels of iron, Fe2+, and MDA, and increased GSH level in mouse model and cell model. The TGF-ß and Smad3 signaling was inhibited by PM2.5. ROS inhibitor NAC reversed PM2.5-regulated ROS and ferroptosis in primary mouse lung epithelial cells. Conclusions: Therefore, we concluded that PM2.5 exposure induced lung injury and fibrosis by inducing ferroptosis via TGF-ß signaling.

RNA-binding motif protein 10 represses tumor progression through the Wnt/ß- catenin pathway in lung adenocarcinoma.

RNA-binding motif protein 10 (RBM10), one of the members of the RNA-binding protein (RBP) family, has a tumor suppressor role in multiple cancers. However, the functional role of RBM10 in lung adenocarcinoma (LUAD) and the underlying molecular mechanism remains unclear. In this study, we observed that RBM10 is significantly downregulated in LUAD tissues compared with normal tissues. Low RBM10 expression is significantly associated with poor outcome of LUAD patients. In vitro and in vivo experiments show that RBM10 inhibits cell proliferation, metastasis and EMT progression in LUAD. Mechanistically, we demonstrate that RBM10 interacts with ß-catenin interacting protein 1 (CTNNBIP1) and positively regulates its expression, disrupting the binding of ß-catenin to the transcription factor TCF/LEF, thereby inactivating the Wnt/ß-catenin pathway. In conclusion, this is the first study reporting the role of RBM10 in suppressing LUAD progression at least via partly inactivating the Wnt/ß-catenin pathway, which provides new insights into the tumorigenesis and metastasis of LUAD. Thus, RBM10 may be a promising new therapeutic target or clinical biomarker for LUAD therapy in the future.

The combination of pretreatment prognostic nutritional index and neuron-specific enolase enhances prognosis predicting value of small cell lung cancer.

INTRODUCTION: Tumor and immune-inflammatory biomarkers have been demonstrated to be closely associated with cancer prognosis. OBJECTIVE: The present study aims to assess the prognostic value of pretreatment prognostic nutritional index (PNI), carcinoembryonic antigen (CEA), and neuron-specific enolase (NSE) in small cell lung cancer (SCLC). METHODS: A retrospective analysis of 301 SCLC patients treated with platinum-based chemotherapy was performed. Overall survival (OS) was assessed by Kaplan-Meier and multivariate Cox hazard analyses. RESULTS: The median OS for total cases was 15.0 months. On univariate analysis, tumor stage (P < 0.001), pretreatment PNI (P < 0.001), CEA (P = 0.039), NSE (P = 0.010), distant metastasis numbers (P < 0.001), and thoracic radiotherapy (P < 0.001) were found to be the predictors of OS. Multivariate analysis showed limited stage, high PNI, NSE < 15 µg/L, and chemoradiotherapy were positive independent prognostic factors (P < 0.05). Low PNI and NSE ≥ 15 µg/L were closely correlated with a high tumor burden status. Three cohorts of SCLC with significant different survival outcomes were divided based on variable PNI and NSE levels. Patients with high PNI and NSE < 15 µg/L showed the best OS of 24.5 months, while patients with low PNI and NSE ≥ 15 µg/L had the worst survival outcome of 10.0 months. Patients with low PNI and NSE < 15 µg/L or high PNI and NSE ≥ 15 µg/L had the similar outcome of 16.5 and 17.0 months, respectively. CONCLUSIONS: Pretreatment PNI and NSE were independent prognostic factors of SCLC. The combination of PNI and NSE enhanced the OS predicting ability, and patients with high PNI and NSE < 15 µg/L had the best survival outcome.

High systemic immune-inflammation index is a predictor of poor prognosis in patients with nonsmall cell lung cancer and bone metastasis.

Aim: This study aimed to evaluate whether systemic immune inflammation (SII) is correlated with overall survival (OS) in patients with nonsmall cell lung cancer (NSCLC) and bone metastasis. Settings and Design: This was a retrospective analysis of the value of pretreatment SII in patients with NSCLC and bone metastasis. Subjects and Methods: Two hundred and thirty-four patients with pathologically confirmed NSCLC and bone metastasis treated at Harbin between January 2008 and May 2010 were included. Baseline clinical characteristics and pretreatment SII were collected for further analysis. Statistical Analysis Used: Receiver operating characteristic curve analysis was used to calculate the optimal cutoff value for SII. Survival analysis was performed using the Kaplan-Meier method. Factors associated with OS were identified by univariate and multivariate analyses. Results: The optimal cutoff value for pretreatment SII was 618.3 × 109/L. Pretreatment SII ≥618.3 × 109/L was more commonly seen in patients with a greater number of distant metastases (<2 vs. ≥2, 56.4% vs. 70.0%, P = 0.033). Univariate analysis showed that sex, tumor histology, Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) score, pretreatment SII, and systemic chemotherapy were associated with OS (P < 0.05). Multivariate analysis showed that sex (hazard ratio [HR] = 1.349, 95% confidence interval [CI] = 1.029-1.708, P = 0.030), ECOG-PS (HR = 1.674, 95% CI = 1.256-2.232, P < 0.001), SII (HR = 1.456, 95% CI = 1.100-1.927, P = 0.009), and systemic chemotherapy (HR = 0.596, 95% CI = 0.437-0.813, P = 0.001) were independent prognostic factors. Subgroup analyses found that SII was prognostic for patients with the following characteristics: age <65 years (P = 0.002), female (P = 0.021), nonsmoker (P = 0.010), histology of adenocarcinoma (P = 0.022), ECOG-PS <2 (P = 0.013), two or more distant metastases (P = 0.004), and two or more bone metastases (P = 0.009). Conclusions: Pretreatment SII may be a prognostic biomarker for NSCLC and bone metastasis.

High prognostic nutritional index (PNI) as a positive prognostic indicator for non-small cell lung cancer patients with bone metastasis.

INTRODUCTION: Increasing evidence shows the close association between prognostic nutritional index (PNI) and overall survival (OS) of solid cancers including lung cancer. However, the role of PNI in non-small cell lung cancer patients (NSCLC) with bone metastasis remains unclear. OBJECTIVE: To explore the prognostic role of PNI in NSCLC patients with bone metastasis. METHODS: A retrospective analysis of 259 initially diagnosed NSCLC with bone metastasis was conducted. Univariate and multivariate analysis were used to assess the potential prognostic roles of parameters. RESULTS: The most common symptoms initially presented were cough and chest pain. Two hundred patients (77.2%) received the treatment of bisphosphonates. Patients with low PNI were found in 154 (59.5%) patients. Median survival time for all cases was 286 days. The median OS for patients with low and high PNI was 227 and 389 days, respectively. The 6-month, 1-year and 2-year survival rates for patients with low PNI were 66.2%, 29.9% and 10.4% compared to 79.0%, 52.4% and 26.7% in patients with high PNI level. On univariate analysis, female patients, non-smokers, high PNI and systematic chemotherapy (P < 0.05) were shown to be closely correlated with a better prognosis of NSCLC patients with bone metastasis. Only PNI (P = 0.002), systematic chemotherapy (P = 0.026) and distant metastasis number (P = 0.044) held statistical significance on multivariate analysis. CONCLUSIONS: PNI represents a non-invasive, efficiency and convenient biomarker of NSCLC patients with bone metastasis. High PNI, systematic chemotherapy and distant metastasis number <2 are independent positive prognostic factors of NSCLC patients with bone metastasis.

[Effect of NF-κB Inhibitor PDTC on Proliferation and Apoptosis of Acute Leukemia Cell HL-60].

OBJECTIVE: To explore the effect of nuclear factor kappa-B (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC) on the proliferation and apoptosis of acute leukemia cell HL-60. METHODS: HL-60 cells were cultured with PDTC of 0, 25, 50, 100 µmol/L for 24, 48, 72 h. The inhibition rate of cell proliferation was detected by CCK-8 assay. Cell apoptosis was detected by Hoechst staining. Cell cycle was detected by flow cytometry. The expression of B-cell lymphoma-2 (BCL-2), BCL-2 associated X protein (BAX), cyclinD1, activated cysteinyl aspartate specific proteinase (cleaved caspase 3), cleaved caspase 8 and activation of NF-κB signal pathway related protein was detected by Western blot. RESULTS: After the HL-60 cells were cultured with PDTC of 25, 50, 100 µmol/L for 24, 48, 72 h, the inhibition rate of cell proliferation increased with the enhancement of PDTC concentration at the same time point (r=0.924, P<0.01). At the same PDTC concentration, the inhibition rate of cell proliferation increased with prolonging of time (r=0.952, P<0.01). After HL-60 cell was cultured with PDTC of 25, 50, 100 µmol/L for 48 h, compared with control group, PDTC of 25, 50, 100 µmol/L increased the cell apoptotic rate, arrested cell cycle at G1 phase (P<0.01), the expression of BCL-2, cyclinD1 and p-NF-κB p65 was down-regulated(P<0.05), the expression of BAX, cleaved caspase 3, cleaved caspase 8 was up-regulated(P<0.01). PDTC of 50, 100 µmol/L down-regulated the expression of p-inhibitor of NF-κB (p-IκBα)(P<0.01). CONCLUSION: PDTC can inhibit acute leukemia HL-60 cell proliferation and induce cell apoptosis.

Preparation and Characterization of Iron-Doped Tricalcium Silicate-Based Bone Cement as a Bone Repair Material.

Iron is one of the trace elements required by human body, and its deficiency can lead to abnormal bone metabolism. In this study, the effect of iron ions on the properties of tricalcium silicate bone cement (Fe/C3Ss) was investigated. It effectively solved the problems of high pH value and low biological activity of calcium silicate bone cement. The mechanical properties, in vitro mineralization ability and biocompatibility of the materials were systematically characterized. The results indicate that tricalcium silicate bone cement containing 5 mol% iron displayed good self-setting ability, mechanical properties and biodegradation performance in vitro. Compared with pure calcium silicate bone cement (C3Ss), Fe/C3Ss showed lower pH value (8.80) and higher porosity (45%), which was suitable for subsequent cell growth. Immersion test in vitro also confirmed its good ability to induce hydroxyapatite formation. Furthermore, cell culture experiments performed with Fe/C3Ss ion extracts clearly stated that the material had excellent cell proliferation abilities compared to C3Ss and low toxicity. The findings reveal that iron-doped tricalcium silicate bone cement is a promising bioactive material in bone repair applications.

Identification of an Immune Gene Expression Signature for Predicting Lung Squamous Cell Carcinoma Prognosis.

Growing evidence indicates that immune-related biomarkers play an important role in tumor processes. This study investigates immune-related gene expression and its prognostic value in lung squamous cell carcinoma (LUSC). A cohort of 493 samples of patients with LUSC was collected and analyzed from data generated by the TCGA Research Network and ImmPort database. The R coxph package was employed to mine significant immune-related genes using univariate analysis. Lasso and stepwise regression analyses were used to construct the LUSC prognosis prediction model, and clusterProfiler was used for gene functional annotation and enrichment analysis. The Kaplan-Meier analysis and ROC were used to evaluate the model efficiency in predicting and classifying LUSC case prognoses. We identified 14 immune-related genes to incorporate into our prognosis model. The patients were divided into two subgroups (Risk-H and Risk-L) according to their risk score values. Compared to Risk-L patients, Risk-H patients showed significantly improved overall survival (OS) in both training and testing sets. Functional annotation indicated that the 14 identified genes were mainly enriched in several immune-related pathways. Our results also revealed that a risk score value was correlated with various signaling pathways, such as the JAK-STA signaling pathway. Establishment of a nomogram for clinical application demonstrated that our immune-related model exhibited good predictive prognostic performance. Our predictive prognosis model based on immune signatures has potential clinical implications for assessing the overall survival and precise treatment for patients with LUSC.

Boosting Circularly Polarized Luminescence of Organic Conjugated Systems via Twisted Intramolecular Charge Transfer.

Realizing a high luminescence dissymmetry factor (g lum) is a paramount yet challenging issue in the research field of circularly polarized luminescence (CPL). Here, we reported a novel set of organic conjugated systems with twisted intramolecular charge transfer (TICT) characteristics based on conjugated o-carborane-binaphthyl dyads composing of binaphthyl units as chiral electron donors and o-carborane units as achiral electron acceptors, demonstrating intense CPL with large g lum values. Interestingly, single-crystalline o-1 exhibited a high-level brightness and a large g lum factor as high as +0.13, whereas single-crystalline o-2 processed a relatively low brightness with a decreased g lum value to -0.04. The significant diversity of CPL-active properties was triggered by the selective introduction of o-carborane units onto the binaphthyl units. Benefiting from the large magnetic dipole transition moments in TICT states, the CPL activity of TICT o-carborane-based materials exhibited amplified circular polarization. This study provides an efficient molecular engineering strategy for the rational design and development of highly efficient CPL-active materials.

High Systemic Immune-Inflammation Index (SII) Represents an Unfavorable Prognostic Factor for Small Cell Lung Cancer Treated with Etoposide and Platinum-Based Chemotherapy.

PURPOSE: Systemic immune-inflammation index (SII) has been demonstrated to be closely associated with prognosis of a series of solid tumors. However, its role in small cell lung cancer (SCLC) remains poorly understood. The present study aims to evaluate the prognostic significance of pretreatment SII in SCLC treated with etoposide and platinum-based chemotherapy. METHODS: Sixty hundred and fifty-three newly diagnosed SCLC patients were enrolled. The optimal cut-off values for SII and LDH (lactate dehydrogenase) were obtained by a receiver operating characteristic (ROC) curve analysis. Overall survival (OS) was assessed by univariate and multivariate analyses. RESULTS: The optimal cut-off values of pretreatment SII and LDH were 748.51 × 109/L and 188.5 U/L, respectively. High pretreatment SII was significantly associated with advanced tumor stage (limited disease, LD vs. extensive disease, ED; 26.3% vs 46.5%; p < 0.001). On univariate analysis, age < 65 years, female, non-smoker, limited disease, SII < 748.51 × 109/L, LDH < 188.5 U/L, distant metastasis numbers < 2, chemotherapy + radiotherapy, and chemotherapy + surgery were closely correlated with a prolonged OS (p < 0.05). The median OS for patients in high SII group was 12.0 months, compared with that of 17.0 months for patients in low SII group. Multivariate analysis showed smoking history (p = 0.014), tumor stage (p < 0.001), pretreatment SII (p < 0.001), LDH (p = 0.002), distant metastasis numbers (p = 0.006), and chemotherapy + radiotherapy (p < 0.001) were independent prognostic factors of OS. Furthermore, SII remained prognostic significance for SCLC stratified by variable subgroups analysis. CONCLUSION: Pretreatment SII represents a powerful prognostic biomarker for SCLC patients treated with etoposide and platinum-based chemotherapy. It is significant for treatment strategy making in clinics.

TBL1XR1 is involved in c-Met-mediated tumorigenesis of human nonsmall cell lung cancer.

Nonsmall cell lung carcinoma (NSCLC) contributes to the highest number of cancer deaths globally. Metastases and chemoresistance are two major confounders to the treatment efficacy in NSCLC. Transducin (ß)-like 1 X-linked receptor 1 (TBL1XR1) has been associated with high rates of metastases in breast, gastric, and stomach cancers. However, the role of TBL1XR1 in lung cancers remains underexplored. We selected matched and cancerous lung tissues to establish the upregulation of TBL1XR1. Using in vitro assays, we assessed the influence of TBL1XR1 on various cancer phenotypes, namely cell proliferation, chemoresistance, invasion, and metastases in a CRISPR-Cas9-mediated knock out model (A549 cells), and H460 cell lines overexpressing TBL1XR1. We found that TBL1XR1 is overexpressed in NSCLC tissue and patient sera in comparison to paired adjacent normal tissue. Overexpression of TBL1XR1 in NSCLC cell lines mediates cell survival, proliferation, and metastases. TBL1XR1 was found to regulate MEK and Akt pathways through their master regulator c-Met. We observed that activation of c-Met is downregulated in the absence of TBL1XR1. Our study strengthens the contention that TBL1XR1 is a biomarker for prognosis of NSCLC. It may also be considered as an adjunct or core therapeutic target to overcome cisplatin resistance in lung cancers.

FAM83A signaling induces epithelial-mesenchymal transition by the PI3K/AKT/Snail pathway in NSCLC.

Family with sequence similarity 83, member A (FAM83A), as a potential tumor promoter, was reported to contribute to the progression of several malignant tumors. However, the significance of FAM83A in invasion and metastasis of non-small cell lung cancer (NSCLC) remains largely unknown. In this study, we found that FAM83A expression was significantly increased in NSCLC tissues. High expression of FAM83A was positively associated with tumor metastasis and poor survival of NSCLC patients. Functional experiments revealed that FAM83A knockdown could suppress NSCLC cell migration and invasion both in vivo and in vitro. While opposite results were observed in FAM83A-transfected cells. Mechanically, we found that FAM83A promoted NSCLC cell migration and invasion by inducing epithelial-mesenchymal transition (EMT) via PI3K/ATK/Snail signaling. Rescue experiment demonstrated that inhibition of either AKT or Snail could partially counteract the promoting effect of FAM83A overexpression in NSCLC metastasis. Taken together, our findings are the first time to demonstrate that increased expression of FAM83A in NSCLC was correlated with EMT and tumor metastasis, which may provide a novel therapeutic target in NSCLC treatment.

Clinical impact of pretreatment prognostic nutritional index (PNI) in small cell lung cancer patients treated with platinum-based chemotherapy.

INTRODUCTION: Numbers of prognostic factors of small cell lung cancer (SCLC) have been demonstrated in previous studies. However, the identification of biomarkers with easy access, convenience, and low consumption is of great value in clinics. OBJECTIVES: In order to find such a biomarker, a single institution study with 1156 SCLC patients was retrospectively conducted to assess the prognostic value of prognostic nutritional index (PNI) on SCLC patients treated with platinum-based chemotherapy. METHODS: The optimal cut-off values were determined by a receiver operating characteristic (ROC) curve analysis. Univariate and multivariate analyses were used to assess their prognostic values for overall survival (OS). RESULTS: On univariate analysis, age, smoking history, tumor stage, PNI, radiotherapy, and surgery were significantly associated with OS. Age, stage, PNI, radiotherapy, and surgery held statistical significance on multivariate analysis. High PNI was closely associated with younger age, limited disease, and radiotherapy. PNI was also demonstrated to be an independent prognostic factor in subgroups analysis, especially in patients with age ≤ 60, no smoking history, no family history of tumor, and no radiotherapy. CONCLUSIONS: Age ≤ 60 years, limited disease, high PNI, radiotherapy, and surgery were independent positive prognostic factors of SCLC patients treated with chemotherapy. PNI was a good biomarker for the assessment of SCLC prognosis for its easy access, convenience to be calculated, and low consumption. Pretreatment PNI can better predict the prognosis of SCLC, especially in patients with age ≤ 60, no smoking history, no family history of tumor, and no radiotherapy.

The expression and clinical significance of microRNA-1258 and heparanase in human breast cancer.

OBJECTIVES: To investigate the expression profile of miR-1258 and heparanase (HPSE) in breast cancer and to assess their clinicopathological significance. DESIGN AND METHODS: The expression levels of miR-1258 and HPSE were analyzed in normal, benign and malignant breast tissues. Their serum levels were evaluated in healthy women and in patients with benign and malignant breast disease. We studied the correlation between the expression of miR-1258 and HPSE and the clinical features presented by the patients. RESULTS: MiR-1258 was down-regulated and HPSE was up-regulated in breast cancer, with a significant inverse correlation. A reduced miR-1258 expression and an elevated HPSE expression were associated with the lymph node status, late clinical stages, a short overall survival and a short relapse-free survival. In frozen fresh tissue samples, the miR-1258 levels in breast cancer with lymph node metastasis were significantly lower than that of breast cancer without lymph node metastasis and benign disease (BD). In contrast, the HPSE levels in breast cancer with lymph node metastasis were the highest. In serum samples, the miR-1258 levels in metastatic breast cancer (M1) were lower than that of primary breast cancer (M0) and BD. However, serum HPSE levels of M1 patients were significantly higher than that of M0 patients and BD patients. CONCLUSIONS: MiR-1258 may play an important role in breast cancer development and progression by regulating the expression of HPSE, and they might be potential prognostic biomarkers for breast cancer.

High expression of CD147 and MMP-9 is correlated with poor prognosis of triple-negative breast cancer (TNBC) patients.

The aim of this study was to investigate expression of CD147 and MMP-9 in triple-negative breast cancer (TNBC) so as to determine whether these two proteins may be correlated with poor prognosis of TNBC patients. We examined the expression levels of the CD147 and MMP-9 in 127 patients with TNBC and 30 patients with mammary gland fibroma using immunohistochemical staining before any treatments. Furthermore, we analyzed the correlation between the expression of these two proteins and various clinicopathologic factors including survival status of patients with TNBC. Positive stain of CD147 and MMP-9 was observed in all samples of TNBC. A statistically positive correlation was observed between the expression levels of CD147 and MMP-9 in TNBC tissues. The incidences of high expression were 48.0 % for CD147 and 53.5 % for MMP-9 in 127 TNBC tissues, respectively. High expression of either CD147 or MMP-9 was significantly correlated with clinical feature and shorter progression-free survival (PFS) (P(CD147) = 0.039; P(MMP-9) = 0.017) and overall survival (OS) (P(CD147) = 0.037; P(MMP-9) = 0.023). The expression levels of CD147 and MMP-9 are positively correlated with invasion, metastasis and shorter PFS/OS of TNBC. Patients with high expression of CD147 and MMP-9 had poor prognosis than TNBC patients with low expression.

The expression and clinical significance of the androgen receptor and E-cadherin in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) has a poor prognosis and lacks prognostic indicators. The androgen receptor (AR) and E-cadherin are involved in the pathogenesis of breast cancer, but their roles are not clearly defined. We designed this study to evaluate AR and E-cadherin expression and to determine their relationships with the clinicopathologic parameters of triple-negative breast cancer. The present study included 127 TNBC patients. Immunohistochemical stains for AR and E-cadherin were performed, and the relationships between AR and E-cadherin expression and clinicopathologic data and prognosis were analyzed. We found that in TNBC patients, AR was expressed in 16(12.6%) cases, and E-cadherin was expressed in 41(33.0%) cases. AR expression was associated with tumor grade (P = 0.004) and menopausal status (P = 0.017), and E-cadherin expression was associated with node status (P= 0.016). A multivariate analysis demonstrated that tumor size, tumor grade, lymph node status, and E-cadherin were of prognostic significance for disease-free interval and overall survival. Compared with AR-positive patients, AR-negative patients showed significantly poorer outcomes with respect to the disease-free interval (P = 0.047) and overall survival (P = 0.038). E-cadherin-negative patients experienced shorter disease-free interval (P = 0.016) and poorer overall survival (P = 0.012) than did E-cadherin-positive patients. An AR-positive and E-cadherin-negative expression profile was associated with recurrence or metastasis (P = 0.036). Moreover, as the expression of nuclear AR increased (25% vs. 33.3%, P = 0.361), less E-cadherin staining was observed in TNBC samples. This finding suggested that AR and E-cadherin expression could be a useful prognostic marker for classifying subgroups of TNBC.

Down-regulation of ICBP90 contributes to doxorubicin resistance.

Acquired resistance to doxorubicin has become a serious obstacle in breast cancer treatment. The underlying mechanism responsible for this has not been completely elucidated. In this study, a doxorubicin-resistant MCF-7/Dox cell was developed to mimic the occurrence of acquired doxorubicin resistance. We next contrasted the expression profiles of ICBP90 and Topo IIα and tumor cell growth of different breast cancer cell lines to doxorubicin. Decreased expression levels of ICBP90 and Topo IIα were found in doxorubicin-resistant cells. To examine its function in chemoresistance, RNA interference (RNAi) and forskolin stimulation experiments further demonstrated that ICBP90 and Topo IIα were involved in the proliferation of cells that had acquired doxorubicin resistance. In MCF-7/Dox and ICBP90-siRNA cells, the cell growth wasn't inhibited by doxorubicin and preferentially arrested in G1 phase. However, after forskolin increased the Topo IIα expression, these breast cancer cells were again found to be inhibited by doxorubicin. Further, immunohistochemical assay breast cancer patients accepted EFC regimen showed ICBP90 was significantly associated with tumor cell proliferation, locally advanced disease and Topo IIα expression. In conclusion, down-regulation of ICBP90 induced the descended expression of Topo IIα protein which is the target enzyme of doxorubicin.