Metabolic Heterogeneity and Potential Immunotherapeutic Responses Revealed by Single-Cell Transcriptomics of Breast Cancer.

BACKGROUND: Breast cancer (BC) exhibits remarkable heterogeneity. However, the transcriptomic heterogeneity of BC at the single-cell level has not been fully elucidated. METHODS: We acquired BC samples from 14 patients. Single-cell RNA sequencing (scRNA-seq), bioinformatic analyses, along with immunohistochemistry (IHC) and immunofluorescence (IF) assays were carried out. RESULTS: According to the scRNA-seq results, 10 different cell types were identified. We found that Cancer-Associated Fibroblasts (CAFs) exhibited distinct biological functions and may promote resistance to therapy. Metabolic analysis of tumor cells revealed heterogeneity in glycolysis, gluconeogenesis, and fatty acid synthetase reprogramming, which led to chemotherapy resistance. Furthermore, patients with multiple metastases and progression were predicted to benefit from immunotherapy based on a heterogeneity analysis of T cells and tumor cells. CONCLUSIONS: Our findings provide a comprehensive understanding of the heterogeneity of BC, provide comprehensive insight into the correlation between cancer metabolism and chemotherapy resistance, and enable the prediction of immunotherapy responses based on T-cell heterogeneity.

Long noncoding RNA HOTAIR promotes breast cancer development through the lncRNA HOTAIR/miR-1/GOLPH3 axis

Background The lncRNA HOTAIR is frequently overexpressed in breast cancer tissues and plays an important role in the development of breast cancer. Here, we investigated the effect of the lncRNA HOTAIR on the biological behaviour of breast cancer cells and its molecular mechanism. Methods We investigated the level of HOTAIR in breast cancer and its clinical pathological characteristics by bioinformatic methods. Then, we evaluated the effects of HOTAIR and miRNA-1 expression on the biological behaviour of breast cancer cells by qPCR, Cell Counting Kit-8 (CCK-8) assay, clonogenic assays, Transwell assay and flow cytometry for cell proliferation, invasion migration and apoptosis, and cell cycle analysis. Finally, the target genes of the lncRNA HOTAIR/miR-1/GOLPH3 regulatory axis were validated by luciferase reports. Results The expression of HOTAIR in breast cancer tissues was significantly higher than that in normal breast tissues (P < 0.05). Silencing of HOTAIR suppressed cell proliferation, invasion and migration, promoted apoptosis and induced G1 phase block in breast cancer (P < 0.0001). We also verified that miR-1 is a target of HOTAIR and that GOLPH3 is a target of miR-1 by luciferase reporter assays (P < 0.001). Conclusions The expression of HOTAIR was significantly elevated in breast cancer tissues. Reducing the expression of HOTAIR inhibited the proliferation, invasion and migration of breast cancer cells and promoted apoptosis, and the mechanism was mainly the effect of the lncRNA HOTAIR/miR-1/GOLPH3 regulatory axis on the biological behaviour of breast cancer cells (AU)

Efficacy and safety of utidelone plus capecitabine in advanced first-line therapy for metastatic breast cancer: A multicenter real-world study.

Background: The purpose of this study was to compare the efficacy and safety of utidelone plus capecitabine for advanced first-line versus second-line or above therapy in metastatic breast cancer patients who had previously received anthracycline and taxane. At the same time, we compared the efficacy of utidelone plus capecitabine and vinorelbine plus cisplatin in advanced first-line treatment of metastatic breast cancer. Patients and methods: A retrospective cohort of 11 patients with metastatic breast cancer previously treated with anthracycline and taxane (including neoadjuvant and adjuvant therapies) for advanced first-line with utidelone plus capecitabine, 32 patients treated with second-line or above, and 60 patients with vinorelbine plus cisplatin between October 2011 and August 2022 was collected. The first and second groups were treated with utidelone plus capecitabine, and the third group was treated with vinorelbine plus cisplatin. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS), objective response rate (ORR), and treatment safety. Results: By 03/31/2023, median PFS reached 11.70 months (95 % CI 0.093-0.141) in utidelone plus capecitabine group in the advanced first-line therapy, compared to 5.60 months (95 % CI 0.025-0.079) in the second-line or above therapy [HR 0.42, (95 % CI 0.226-0.787), P = 0.0077]. In utidelone plus capecitabine, the median OS was not reached in the advanced first-line therapy, with a mean overall survival of 23.16 months (95 % CI 0.198-0.265); whereas the median OS in the second-line or above therapy was 19.50 months (95 % CI 0.083-0.307), with a mean overall survival of 16.89 months (95 % CI 0.136-0.202) [HR 0.26, (95 % CI 0.098-0.678), P = 0.0495]. The ORR for advanced first-line therapy was 27.27 % (95%CI 0.060, 0.610) compared with 15.63 % (95%CI 0.053, 0.328) for second-line or above. In advanced first-line therapy, utidelone plus capecitabine was superior to vinorelbine plus cisplatin with a median PFS of 6.12 months (95 % CI 0.051-0.072) [HR 0.49, (95 % CI 0.286-0.839), P = 0.0291]. Compared with utidelone plus capecitabine, the median OS in vinorelbine plus cisplatin advanced first-line therapy group was 35.37 months (95 % CI 0.258-0.449), and the mean overall survival was 40.79 months (95 % CI 0.315-0.501) [HR 0.54, (95 % CI 0.188-1.568), P = 0.2587]. The ORR for vinorelbine plus cisplatin was 18.33 % (95 % CI 0.095, 0.304). The most common adverse events in our study were neurological toxicity, hand-foot syndrome, hematological toxicity, gastrointestinal toxicity, and hepatic and renal function abnormalities. There were no deaths due to adverse effects during the utidelone plus capecitabine treatment period. Conclusions: In MBC, advanced first-line therapy with utidelone plus capecitabine resulted in more favorable PFS, OS, and ORR than second-line or above therapy. In advanced first-line therapy, utidelone plus capecitabine had superior PFS, and ORR compared with vinorelbine plus cisplatin. This study concludes that utidelone plus capecitabine is a more valuable chemotherapy option in advanced first-line MBC.

Long noncoding RNA HOTAIR promotes breast cancer development through the lncRNA HOTAIR/miR-1/GOLPH3 axis.

BACKGROUND: The lncRNA HOTAIR is frequently overexpressed in breast cancer tissues and plays an important role in the development of breast cancer. Here, we investigated the effect of the lncRNA HOTAIR on the biological behaviour of breast cancer cells and its molecular mechanism. METHODS: We investigated the level of HOTAIR in breast cancer and its clinical pathological characteristics by bioinformatic methods. Then, we evaluated the effects of HOTAIR and miRNA-1 expression on the biological behaviour of breast cancer cells by qPCR, Cell Counting Kit-8 (CCK-8) assay, clonogenic assays, Transwell assay and flow cytometry for cell proliferation, invasion migration and apoptosis, and cell cycle analysis. Finally, the target genes of the lncRNA HOTAIR/miR-1/GOLPH3 regulatory axis were validated by luciferase reports. RESULTS: The expression of HOTAIR in breast cancer tissues was significantly higher than that in normal breast tissues (P < 0.05). Silencing of HOTAIR suppressed cell proliferation, invasion and migration, promoted apoptosis and induced G1 phase block in breast cancer (P < 0.0001). We also verified that miR-1 is a target of HOTAIR and that GOLPH3 is a target of miR-1 by luciferase reporter assays (P < 0.001). CONCLUSIONS: The expression of HOTAIR was significantly elevated in breast cancer tissues. Reducing the expression of HOTAIR inhibited the proliferation, invasion and migration of breast cancer cells and promoted apoptosis, and the mechanism was mainly the effect of the lncRNA HOTAIR/miR-1/GOLPH3 regulatory axis on the biological behaviour of breast cancer cells.

Study on the correlation between B vitamins and breast cancer.

BACKGROUND: Relevant studies suggest that serum vitamin level is related to the risk of breast cancer, and dietary pattern and drug supplementation can significantly affect the level of vitamin in the body. Therefore, intervention of vitamin level in the body is expected to be a potential strategy to reduce the risk of breast cancer. However, the current epidemiological findings of serum vitamin levels and breast cancer risk are inconsistent, and the relationship between serum vitamin and breast cancer is still controversial. In this study, we compared the serum vitamin expression levels of healthy people, benign breast patients, and breast cancer patients, and evaluated the relationship between B vitamin levels and breast cancer risk. METHODS: The study used liquid chromatography-tandem mass spectrometry to determine the serum vitamin levels of 520 people who attended Yunnan Cancer Hospital from September 2020 to December 2020. After screening by exclusion criteria, 38 patients with benign breast diseases, 87 patients with breast cancer and 91 healthy controls were finally included. The kruskal-wallis H test was used to compare the differences in serum vitamin levels of subjects. Χ2 test was used to evaluate the relationship between B vitamin level and age,BMI,TNM staging,Ki-67,Her-2,surgery and chemotherapy, and other baseline characteristics and through binary logistic regression analysis, calculating odds ratio and 95% confidence interval (CI) to evaluate the relationship between B vitamins and breast cancer risk. CONCLUSION: The levels of VitB1 and VitB5 in the serum of breast cancer patients and patients with benign breast diseases were higher than those in the healthy control group, while the expression levels of VitB3 in breast cancer patients were lower than those in the healthy control group and the breast benign disease groups. The level of VitB1 was positively correlated with breast cancer risk. The VitB3 level was negatively correlated with breast cancer risk. The VitB5 level is not significantly related to the risk of breast cancer.

Three-dimensional ultrasound integrating nomogram and the blood flow image for prostate cancer diagnosis and biopsy: A retrospective study.

Backgrounds: Prostate cancer (PCa) is the second most common male cancer in the world and based on its high prevalence and overwhelming effect on patients, more precise diagnostic and therapeutic methods are essential research topics. As such, this study aims to evaluate the value of three-dimensional transrectal ultrasound (3D-TRUS) in the detection, diagnosis and biopsy of PCa, and to provide a basis for clinical practice of PCa. Methods: Retrospective analysis and comparison of a total of 401 male patients who underwent prostate TRUS in our hospital from 2019 to 2020 were conducted, with all patients having prostate biopsy. Nomogram was used to estimate the probability of different ultrasound signs in diagnosing prostate cancer. The ROC curve was used to estimate the screening and diagnosis rates of 3D-TRUS, MRI and TRUS for prostate cancer. Results: A total of 401 patients were randomly divided into two groups according to different methods of prostate ultrasonography, namely the TRUS group (251 patients) and the 3D-TRUS group (150 patients). Of these cases, 111 patients in 3D-TRUS group underwent MRI scan. The nomogram further determined the value of 3D-TRUS for prostate cancer. The ROC AUC of prostate cancer detected by TRUS, MRI and 3D-TRUS was 0.5580, 0.6216 and 0.6267 respectively. Biopsy complications were lower in 3D-TRUS group than TRUS group, which was statistically significant (P<0.005). Conclusions: The accuracy of 3D-TRUS was higher in diagnosis and biopsy of prostate cancer. Meanwhile, the positive rate of biopsy could be improved under direct visualization of 3D-TRUS, and the complications could be decreased markedly. Therefore, 3D-TRUS was of high clinical value in diagnosis and biopsy of prostate cancer.

A comparison of Chinese multicenter breast cancer database and SEER database.

There are different characteristics of BC in developing countries and developed countries. We intended to study the factors which influence the survival and prognosis of BC between southern China and the United States. (a) To study the two groups BC patients in southern China from 2001 to 2016 and SEER database from 1975 to 2016. (b) To register, collect and analyze the clinicopathological features and treatment information. Our study found that there are significant differences in tumor size, positive lymph node status and KI-67 between southern China and SEER cohort (P < 0.000). The positive lymph node status may be one of the causes of difference of morbidity and mortality of BC patients in China. Furthermore, the differences in treatment methods may also account for the differences between China and seer databases.

The Interaction of NTN4 and miR-17-92 Polymorphisms on Breast Cancer Susceptibility in a Chinese Population.

INTRODUCTION: Genome-wide association studies have identified a genetic variant rs17356907 in netrin 4 (NTN4) as a risk locus of breast cancer (BC) in Europeans. NTN4 is a target gene of miR-17-92 cluster that is an oncogenic miRNA in BC development. We aimed to replicate the rs17356907 in a Chinese population and examine the interaction of NTN4 and miR-17-92 on BC susceptibility. MATERIALS AND METHODS: The rs17356907 in NTN4 and 3 additional polymorphisms in the promoter of miR-17-92 (ie, rs9588884, rs982873, and rs1813389) were determined in 415 patients with BC and 420 healthy controls using a TaqMan assay. The expression levels of NTN4 in BC and normal tissues were performed using the quantitative reverse transcription-PCR. RESULTS: With reference to the rs17356907AA genotype, the GG genotype was associated with a decreased risk of BC with an adjusted OR of 0.38 (95% CI: 0.20-0.74). With reference to the rs17356907AA-rs982873CT/CC genotypes, the rs17356907 AG/GG-rs982873CT/CC genotypes were associated with a borderline decreased risk of BC with an adjusted OR of 0.67 (95% CI: 0.48-0.93). Gene-gene interaction analysis showed that the rs17356907-rs982873-rs9588884-rs1813389 was the best model on BC susceptibility. Furthermore, the rs17356907GG genotype displayed higher levels of NTN4 mRNA. CONCLUSIONS: The NTN4 rs17356907 may have a single and interactive effect with miR-17-92 polymorphisms on the risk of BC.

Overexpression of ING3 is associated with attenuation of migration and invasion in breast cancer.

Inhibitor of growth 3 (ING3) has been identified as a potential cancer drug target, but little is known about its role in breast cancer. Thus, the present study aimed to investigate ING3 expression in breast cancer, its clinical value, and how ING3 influences the migration and invasion of breast cancer cells. The Cancer Genome Atlas and UALCAN databases were used to analyze ING3 expression in cancer tissues and normal tissues. Survival analysis was performed using the UALCAN, UCSC Xena and KM-plot databases. In addition, reverse transcription-quantitative PCR and western blot analyses were performed to detect ING3 mRNA and protein expression levels. ING3 was overexpressed via lentiviral vector transfection, while the Transwell and wound healing assays were performed to assess the cell migratory and invasive abilities. Protein interaction and pathway analyses were performed using the GeneMANIA and Kyoto Encyclopedia of Genes and Genomes databases, respectively. The results demonstrated that ING3 expression was significantly lower in cancer tissues compared with normal tissues (P<0.05). In addition, luminal A and human epidermal growth factor receptor 2 (HER2)-enriched breast cancer tissues expressed lower levels of ING3 compared with normal breast tissues. Notably, statistically significant differences were observed in long-term survival between patients with luminal A (P=0.04) and HER2-enriched (P=0.008) breast cancer, with high and low expression levels of ING3. The results of the Transwell migration and invasion assays demonstrated that overexpression of ING3 significantly inhibited the migratory and invasive abilities of MCF7 (P<0.05) and HCC1937 (P<0.05) cells. The results of the wound healing assay demonstrated that the percentage wound closure significantly decreased in cells transfected with LV5-ING3 compared with the negative control group at 12 h (P<0.05) and 24 h (P<0.01). The PI3K/AKT, JAK/STAT, NF-κB and Wnt/ß-catenin pathways are the potential pathways regulated by ING3. Notably, overexpression of ING3 inhibited migration and invasion in vitro. However, further studies are required to determine whether ING3 regulates the biological behavior of breast cancer via tumor-related pathways.

Evaluation of the body mass index in breast cancer prognosis in a cohort of small-stature overweight patients: multi-center study in China.

BACKGROUND: Overweight and obesity have become a major health issue in the past 30 years. Several studies have already shown that obesity is significantly associated with a higher risk of developing breast cancer. However, few studies have assessed the prognostic value of the body mass index (BMI) in Asian populations. The purpose of this study was to retrospectively analyze the impact of BMI on the prognosis of breast cancer in overweight, under 160 cm tall patients from southern China. METHODS: We retrospectively analyzed data from 525 breast cancer patients diagnosed between 2003 to 2010 in a multi-center of China. After applying the exclusion criteria, 315 patients with complete data were retained. Their clinical and pathological characteristics were compared using the chi-square test. Survival analysis was performed with the Kaplan-Meier method. Univariate and multivariate analyses were performed using Cox regression to calculate hormone receptor status, HER-2 status, lymph node status, age, BMI and tumor size hazard ratio (HR), and 95% confidence intervals (95% CI). RESULTS: There was a strong correlation between BMI and age in the baseline feature analysis (P=0.001). After grouping the patients according to the molecular type of cancer, we found that in Luminal A and B, the BMI was related to age (P=0.002, P=0.010). The disease-free survival (DFS) and overall survival (OS) of patients with different BMI were not significantly different. This conclusion was also reached by pairwise comparison of subgroups. There was no significant difference in recurrence in patients from different BMI groups. We did not find a critical weight threshold associated with higher risk of recurrence. There were no statistically significant differences in treatment among the three BMI groups of overweight patients. CONCLUSIONS: We found that the BMI of Chinese breast cancer patients is related to age but not prognosis.

The treatment process of an extremely rare giant borderline phyllodes tumor of breast: case report and literature review.

Giant phyllodes tumors are rare fibroepithelial neoplasms, usually defined as >10 cm. It is often difficult for pathologists to distinguish fibroadenomas from phyllodes tumors and determine the malignant potential level. The current treatment principle is to ensure the extended resection of tumors with a margin of 1 cm or more. For patients with multiple local recurrences or large tumors after surgery, simple mastectomy is recommended. Axillary management should be considered when breast cancer is diagnosed at the same time. We now present a rare case: a female patient found a right breast mass in 2014, and the mass had continued to grow for more than 7 months, and she was ultimately diagnosed with a giant phyllodes tumor with a diameter of 30 cm. Extensive resection is a suitable method to treat smaller phyllodes tumors, but giant phyllodes tumors require mastectomy, so the patient in this case underwent a total mastectomy. We removed the mass completely without destroying the normal tissue and structure. The treatment effect was obvious, and no related adverse events occurred during or after the operation, the postoperative recovery was good, and the patient was discharged once she was verified to be in a stable condition. This case is the first reported case of a patient who had a giant borderline phyllodes tumor with a diameter of 30 cm, underwent total mastectomy, and was followed up for 6 months without recurrence. The long-term effect of the treatment will be further evaluated after 5 years.

Clinical and pathological response to neoadjuvant chemotherapy with different chemotherapy regimens predicts the outcome of locally advanced breast cancer.

BACKGROUND: This retrospective analysis was designed to research whether clinical response partial response (PR)/complete response (CR) and pathological response (PCR) to neoadjuvant chemotherapy can translate into prognosis benefit pathological response in patients with locally advanced breast cancer and whether different chemotherapy regimens will influence the outcomes. METHODS: One hundred and thirty-five patients with breast cancer patients who received neoadjuvant chemotherapy were included in the retrospective analysis. Patients were followed up strictly. Overall survival (OS) was evaluated by the Kaplan-Meier analysis. The comparison of the clinical and pathological characteristics and recurrence was performed using the carried out by chi-squared and Fisher's exact tests. Univariate and multivariate analyses were performed by the Cox regression analysis. RESULTS: Clinical response was strongly correlated with lymph nodes status (P=0.032). The OS comparison of pathological response between the pCR group and non-pCR groups did not exhibit statistically significant differences (P=0.400). A similar non-significant response result was observed in the comparison of clinical response between the PR/CR and SD/PD groups group (P=0.108). Univariate and multivariate analyses did not support clinical response (P=0.156 P=0.095 respectively) or pathological response (P=0.600 P=0.144 respectively) as the predictors of prognosis. There were no significant differences in either the comparison of the clinical response group it seems no statistically significance (P=0.496) or the comparison of the pathological response group (P=0.460). OS analyses across different neoadjuvant chemotherapy regimens demonstrated no significant differences (P=0.307). In the PR/CR and PD/SD comparison of every single regimen, there were no significant differences. However, for patients with PR/CR patients from the comparison of five regimens, namely, TAC, FAC, AC-T, AT and TCBP demonstrated a significant difference (P=0.022). In the group of patients with luminal A breast cancer, the result of the Fisher's exact test approached significant (P=0.059). CONCLUSIONS: Neither PR/CR nor pCR can translate into long-term outcome benefit. PR/CR and PCR are not independent predictors in patients with advanced breast cancer. Patients who received a taxane + anthracycline regimen exhibited a higher recurrence rate than any other regimens, especially those patients with luminal A breast cancer.

Overexpression of serum exosomal HOTAIR is correlated with poor survival and poor response to chemotherapy in breast cancer patients.

To investigate the source of serum exosomal HOTAIR, to uncover the diagnostic and prognostic values of serum exosomal HOTAIR, and to discern the expression of serum exosomal HOTAIR between neoadjuvant chemotherapy and response to tamoxifen therapy. Samples were collected from the Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan. Exosomes were isolated from serum, cell culture medium and tumor tissues. We used transmission electron microscopy and western immunoblotting assay to characterize exosomes, and real-time PCR (qPCR) to assess HOTAIR expression. Neoadjuvant chemotherapy and tamoxifen therapy were carried out according to established guidelines. Breast cancer patients expressed higher serum exosomal HOTAIR than did healthy individuals (P\0.001). Serum exosomal HOTAIR levels 3 months after surgery were markedly decreased compared with levels before surgery (P\0.001), and the expression level of exosomal HOTAIR in cell culture medium increased with time in both breast cancer cell lines (72 h greater than 48 h greater than 24 h, 48 h vs 24 h [ [P less than 0.05]; 72 h vs 24 h [P less than 0.01]. Expression of serum exosomal HOTAIR in nude mice was notably greater than in the mock control group (P less than 0.001). The results of the ROC analysis revealed an AUC for serum exosomal HOTAIR of 0.9178 with a 95% CI of 0.8407-1.017 (P less than 0.01). The AUC for the CA15-3 cell line was 0.7378 (95% CI, 0.5585-0.9170; P = 0.03). High expression of exosomal HOTAIR led to a worse disease-free survival (P = 0.0481) and overall survival (P = 0.0463). In the high-expression chemotherapy group, six patients achieved a partial response (PR) and eight demonstrated stable disease (SD) and nine patients achieved PR and two SD in the low-expression group (P = 0.048). In the low-expression tamoxifen group, one patient had a recurrence of breast cancer and another 10 patients exhibited no recurrence, while six showed recurrence, and seven had none in the highexpression group (P = 0.035). We isolated exosomes successfully, and demonstrated that serum exosomal HOTAIR originated from primary breast cancer tissue. We conclude that serum exosomal HOTAIR exhibits the potential to be a diagnostic and prognostic biomarker. High expression of serum exosomal HOTAIR was also correlated with poor neoadjuvant chemotherapy and response to tamoxifen therapy.

Long-term comparisons of the efficacy, safety, and pregnancy outcomes of adjuvant tamoxifen plus ovarian function suppression in premenopausal Han and Zhuang Chinese patients with hormone receptor-positive early breast cancer.

OBJECTIVE: To compare the efficacy, safety, and pregnancy outcomes of tamoxifen plus ovarian function suppression (OFS) between Han and Zhuang women with hormone receptor-positive breast cancer. METHODS: A total of 236 Han and 101 Zhuang women with hormone receptor-positive breast cancer who received tamoxifen plus OFS were analyzed retrospectively. Long-term disease-free survival (DFS) and overall survival (OS) were evaluated by Kaplan-Meier analysis, and adverse events and pregnancy outcomes were assessed by χ2 and Fisher's exact-probability tests. RESULTS: There was no significant difference in DFS or OS between Han and Zhuang women (5-year DFS 74.57% and 77.23%, OS 85.59% and 90.01%, respectively). The incidences of endometrial hyperplasia, ovarian cysts, nausea and vomiting, fatty liver, retinitis, and thrombocytopenic purpura were similar in both groups, but Zhuang women had significantly more allergic reactions (6.93% vs. 2.12%). Pregnancy rates among women who attempted pregnancy were similar (Han, 7/138, 5.07%; Zhuang, 2/46, 4.35%). CONCLUSIONS: OFS plus tamoxifen resulted in similar DFS and OS among premenopausal Han and Zhuang women with hormone receptor-positive breast cancer. However, Zhuang women were more likely to experience an allergic reaction. For women with fertility concerns, OFS plus tamoxifen was associated with similar pregnancy rates in Zhuang and Han women.

Expression of GOLPH3 in patients with non-small cell lung cancer and xenografts models.

Increased expression of Golgi phosphoprotein 3 (GOLPH3) has been reported to be associated with several types of human cancer. Patient-derived cancer xenograft models have demonstrated great potential in preclinical studies. In the present study, the link between GOLPH3 expression and survival was examined in patients with non-small cell lung cancer (NSCLC). Patient-derived lung cancer xenograft models were established with two different methods. Lastly, the association between GOLPH3 expression and establishment of the xenograft models was explored. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry analysis were used to examine GOLPH3 expression in 60 NSCLC tissues and matched adjacent non-cancerous tissues (ANT). In addition, tumor pieces from the 60 NSCLC tissues were implanted in the subcutaneous layer and in the subrenal kidney capsule of nude mice. RT-qPCR, histopathology and immunohistochemistry were used to confirm the human origin of the xenograft tumors. RT-qPCR was also used to research the mutation status of GOLPH3 in the xenograft tumors. The results demonstrated that NSCLC tissues had higher expression of GOLPH3, at the mRNA and protein level, compared with ANT. High expression of GOLPH3 correlated with poor survival in patients with NSCLC. Successful engraftment was established for 27 tissues in the subrenal kidney capsule and for 16 in the subcutaneous layer of nude mice. The subrenal kidney capsule group demonstrated significantly higher engraftment rates than the subcutaneous layer group. In addition, higher GOLPH3 expression in the tumor tissues was significantly correlated with higher engraftment rates in mice. In both groups, few xenografts lost the GOLPH3 mutation. In summary, GOLPH3 may be an important diagnosis and prognosis indicator in patients with NSCLC. The genotype and phenotype of the xenograft tumors derived from patient lung cancer tissues exhibited significant similarities to the originating primary tumors. High GOLPH3 expression may promote the successful establishment of xenograft models for NSCLC.

GOLPH3: a novel biomarker that correlates with poor survival and resistance to chemotherapy in breast cancer.

The association between Golgi phosphoprotein 3 (GOLPH3) and clinical pathological characteristics, as well as the clinical outcomes of both neoadjuvant and adjuvant chemotherapies in breast cancer, remain largely unknown. In this study, we investigated the biological role and clinical significance of GOLPH3 in breast cancer. We found that GOLPH3 expression in tumor tissue was higher than that in adjacent noncancerous tissue (ANT) and fibroadenoma. GOLPH3 silencing reduced the migration, invasion, and proliferation of breast cancer cells and promoted apoptosis of the cells. Importantly, patients with high GOLPH3 expression had worse disease-free survival (DFS) and overall survival (OS), and GOLPH3 expression was correlated with clinical pathological characteristics such as molecular subtype, tumor-node-metastasis classification, and age but was not associated with surgery type. Patients with high GOLPH3 expression had poor DFS and OS in every molecular subtype, and an increase in tumor invasion and lymph node metastasis. The risk of recurrence increased with age in patients with high GOLPH3 expression, and surgery type had no influence on patient survival. This is the first study to investigate the correlation between GOLPH3 and response to chemotherapy in breast cancer. Patients with high GOLPH3 expression showed resistance to neoadjuvant and adjuvant chemotherapies, and GOLPH3 overexpression indicated a high risk of recurrence in patients who received adjuvant chemotherapy. These data suggest that GOLPH3 may be a novel biomarker that correlates with poor survival and resistance to chemotherapy in breast cancer.

Heat shock factor 2 is associated with the occurrence of lung cancer by enhancing the expression of heat shock proteins.

Cancer is the leading cause of morbidity and mortality worldwide, particularly lung cancer. Heat shock proteins and their upstream heat shock factors are involved in the occurrence of cancer and have been widely researched. However, the role of heat shock factor 2 (HSF2) in lung cancer remains unclear. In the present study, expression levels of HSF2 in lung cancer tissues from 50 lung cancer patients were detected by reverse transcription quantitative polymerase chain reaction, and 76% (38/50) were upregulated compared with the matched normal tissues. This suggested possible involvement of HSF2 in lung cancer. To additionally investigate the role of HSF2 in lung cancer occurrence, a plasmid encoding HSF2 was constructed. HSF2 was over expressed in normal lung epithelial BEAS-2B cells and lung cancer A549 cells. The results showed that HSF2 overexpression promoted cell proliferation and cell migration in BEAS-2B and A549 cells. Additional experiments showed that the HSF2-induced cell proliferation and cell migration were dependent on induction of HSPs, particularly HSP27 and HSP90, as co-transfection of HSP27 small interfering RNA (siRNA) or HSP90 siRNA attenuated HSF2-induced cell growth and migration. In conclusion, the present study showed that HSF2 is aberrantly expressed in lung cancer, and it may be an upstream regulator of HSPs, which may strongly affect cell growth and cell migration. Additional studies are required to explain the detailed mechanism between lung cancer, HSF2, HSPs and other possible signaling pathways.