Translating and Adapting the DISCERN Instrument Into a Simplified Chinese Version and Validating Its Reliability: Development and Usability Study.

BACKGROUND: There is a wide variation in the quality of information available to patients on the treatment of the diseases afflicting them. To help patients find clear and accessible information, many scales have been designed to evaluate the quality of health information, including the Patient Education Materials Assessment Tool; the Suitability Assessment of Materials for evaluation of health-related information for adults; and DISCERN, an instrument for judging the quality of written consumer health information on treatment choices. These instruments are primarily in English. Few of them have been translated and adapted into simplified Chinese tools for health information assessment in China. OBJECTIVE: This study aimed to translate and adapt DISCERN into the first simplified Chinese version and validate the psychometric properties of this newly developed scale for judging the quality of patient-oriented health information on treatment choices. METHODS: First, we translated DISCERN into simplified Chinese using rigorous guidelines for translation and validation studies. We tested the translation equivalence and measured the content validity index. We then presented the simplified Chinese instrument to 3 health educators and asked them to use it to assess the quality of 15 lung cancer-related materials. We calculated the Cohen κ coefficient and Cronbach α for all items and for the entire scale to determine the reliability of the new tool. RESULTS: We decided on the simplified Chinese version of the DISCERN instrument (C-DISCERN) after resolving all problems in translation, adaptation, and content validation. The C-DISCERN was valid and reliable: the content validity index was 0.98 (47/48, 98% of the items) for clarity and 0.94 (45/48, 94% of the items) for relevance, the Cronbach α for internal consistency was .93 (95% CI 0.699-1.428) for the whole translated scale, and the Cohen κ coefficient for internal consistency was 0.53 (95% CI 0.417-0.698). CONCLUSIONS: C-DISCERN is the first simplified Chinese version of the DISCERN instrument. Its validity and reliability have been attested to assess the quality of patient-targeted information for treatment choices.

The Chinese Version of the Patient Education Materials Assessment Tool for Printable Materials: Translation, Adaptation, and Validation Study.

BACKGROUND: Providing people with understandable and actionable health information can considerably promote healthy behaviors and outcomes. To this end, some valid and reliable scales assessing the patient-friendliness of health education materials, like the PEMAT-P (Patient Education Materials Assessment Tool for printable materials), have been well developed in English-speaking countries. However, the English version of the PEMAT-P has not been translated and adapted into simplified Chinese and validated in mainland China. OBJECTIVE: This study sought to translate the PEMAT-P tool into a simplified Chinese (Mandarin) version (C-PEMAT-P, a Chinese version of the Patient Education Materials Assessment Tool for printable materials) and verify its validity and reliability for assessing the comprehensibility and actionability of health education resources written in simplified Chinese. As a result, the validated C-PEMAT-P could be used to guide health researchers and educators to design more comprehensible and actionable materials for more tailored and targeted health education and interventions. METHODS: We translated the PEMAT-P into simplified Chinese in the following three steps: (1) forward-translating the PEMAT-P into simplified Chinese, (2) back-translating the simplified Chinese version into English, and (3) testing translation equivalence linguistically and culturally by examining the original English version of the PEMAT-P and the back-translated English version of the tool. Any discrepancies between the original English tool and the back-translated English tool were resolved through a panel discussion among the research team of all authors to produce a revised forward-translated Chinese version (C-PEMAT-P). We then evaluated the clarity of construction and wording as well as the content relevance of the C-PEMAT-P using a 4-point ordinal scale to determine its content validity. After that, 2 native Chinese speakers (health educators) used the C-PEMAT-P to rate 15 health education handouts concerning air pollution and health to validate their reliability. We calculated the Cohen coefficient and Cronbach α to determine the interrater agreement and internal consistency of the C-PEMAT-P, respectively. RESULTS: We finalized the translated Chinese tool after discussing the differences between the 2 English versions (original and back-translated) of the PEMAT-P, producing the final Chinese version of the PEMAT-P (C-PEMAT-P). The content validity index of the C-PEMAT-P version was 0.969, the Cohen coefficient for the interrater scoring agreement was 0.928, and the Cronbach α for internal consistency was .897. These values indicated the high validity and reliability of the C-PEMAT-P. CONCLUSIONS: The C-PEMAT-P has been proven valid and reliable. It is the first Chinese scale for assessing the comprehensibility and actionability of Chinese health education materials. It can be used as an assessment tool to evaluate health education materials currently available and a guide to help health researchers and educators design more comprehensible and actionable materials for more tailored and targeted health education and interventions.

Assessing Patients' Critical Health Literacy and Identifying Associated Factors: Cross-sectional Study.

BACKGROUND: Previous studies have revealed that functional health literacy plays a less important role than communicative and critical health literacy (CRHL) and that communicative literacy and CRHL contribute more to better patient self-management. Although improving health literacy has been identified as an approach to fostering community involvement and empowerment, CRHL may be regarded as the neglected domain of health literacy, rarely achieving any focus or interventions that claim to be working toward this outcome. Considering this research background, close scholarly attention needs to be paid to CRHL and its associated factors. OBJECTIVE: This study aimed to assess CRHL and identify essential factors closely associated with the status of CRHL among Chinese patients and to provide some implications for clinical practice, health education, medical research, and public health policy making. METHODS: We conducted this cross-sectional study, which lasted from April 8, 2022, to September 23, 2022, following the steps below. We first designed a 4-section survey questionnaire and then recruited Mandarin Chinese-speaking patients from Qilu Hospital of Shandong University, China, using randomized sampling. Subsequently, we administered the questionnaire via wenjuanxing, the most popular web-based survey platform in China, between July 20, 2022, and August 19, 2022. Finally, we used latent class modeling to analyze the valid data collected to classify the patient participants and identify the factors potentially associated with different CRHL levels. RESULTS: All data in the 588 returned questionnaires were valid. On the basis of the collected data, we classified the patient participants into 3 latent classes of limited, moderate, and adequate CRHL and identified 4 factors associated with limited CRHL, including middle and old age, male sex, lower educational attainment, and low internal drive to maintain one's health. CONCLUSIONS: Using latent class modeling, we identified 3 classes of CRHL and 4 factors associated with limited CRHL among the Chinese study participants. These literacy classes and the predicting factors ascertained in this study can provide some implications for clinical practice, health education, medical research, and health policy making.

Serum Membrane Type 1-Matrix Metalloproteinase (MT1-MMP) mRNA Protected by Exosomes as a Potential Biomarker for Gastric Cancer.

BACKGROUND Our previous research revealed that membrane type 1-matrix metalloproteinase (MT1-MMP) is overexpressed and plays a crucial role in gastric cancer (GC) progression. Exosomes are important for GC carcinogenesis, and the exosomal contents are ideal biomarkers. However, the expression of exosomal MT1-MMP mRNA in serum and its potential significance in GC remains unclear. MATERIAL AND METHODS The expression of exosomal MT1-MMP mRNA in serum of patients with GC, chronic gastritis, or atypical hyperplasia, and healthy controls was detected using real-time quantitative RT-PCR. Serum CEA, CA19-9, and CA72-4 were also measured by electrochemiluminescence assay. RESULTS Exosomes were isolated and identified in serum, and serum exosomal MT1-MMP mRNA was found to be higher in patients with GC compared with healthy controls and patients with chronic gastritis or atypical hyperplasia (all P<0.05). Serum exosomal MT1-MMP mRNA was significantly correlated with tumor diameter, differentiation, Borrmann type, invasion depth, lymphatic metastasis, distal metastasis, and TNM stage. The AUC of exosomal MT1-MMP mRNA was 0.788 (95% CI: 0.714-0.850) with 63.9% sensitivity and 87.1% specificity, and was higher than that of CEA (0.655 (95% CI: 0.573-0.730)). The combination of 2 markers gave an AUC of 0.821 (95% CI: 0.750-0.878), which was better than with the individual marker. The sensitivity, specificity, and positive and negative predictive values were 75.6%, 83.9%, 94.7%, and 47.3%, respectively. Moreover, the multiple logistic regression model showed that tumor diameter, differentiation, invasion depth, and exosomal MT1-MMP mRNA were the risk factors for lymphatic metastasis in GC. CONCLUSIONS Our results characterized serum exosomal MT1-MMP mRNA in GC, providing a foundation for discovering serum exosomes-targeted biomarkers for GC diagnosis.

Baicalein inhibits prostate cancer cell growth and metastasis via the caveolin-1/AKT/mTOR pathway.

Prostate cancer (PCa) is lethal type of genitourinary cancer due to its high morbidity and gradual resistance to androgen deprivation therapy. Accumulating evidence has recently suggested that the daily intake of flavonoids is negatively correlated with the risk of cancer. In this study, we aimed to investigate the potential effects of baicalein on androgen-independent PCa cells and the underlying mechanisms through which baicalein exerts its actions. Cell viability and flow cytometric apoptosis assays indicated that baicalein potently suppressed the growth and induced the apoptosis of DU145 and PC-3 cells in a time- and dose-dependent manner. Consistently, the inhibitory effects of baicalein on migration and invasion were also observed in vitro. Mechanistically, we found that baicalein can suppress caveolin-1 and the phosphorylation of AKT and mTOR in a time- and dose-dependent manner. Moreover, the inhibition of the activation of AKT with LY294002 significantly promoted the apoptosis and metastasis induced by baicalein. In conclusion, these findings suggested that baicalein can induce apoptosis and inhibit metastasis of androgen-independent PCa cells through inhibition of the caveolin-1/AKT/mTOR pathway, which implies that baicalein may be a potential therapeutic agent for the treatment of androgen-independent prostate cancer patients.

Factors Associated With Limited Cancer Health Literacy Among Chinese People: Cross-sectional Survey Study.

BACKGROUND: Limited cancer health literacy may be attributed to various factors. Although these factors play decisive roles in identifying individuals with limited cancer health literacy, they have not been sufficiently investigated, especially in China. There is a pressing need to ascertain the factors that effectively identify Chinese people with poor cancer health literacy. OBJECTIVE: This study aimed to identify the factor associated with limited cancer health literacy among Chinese people based on the 6-Item Cancer Health Literacy Test (CHLT-6). METHODS: We first categorized Chinese study participants according to the answers provided for cancer health literacy as follows: people who provided ≤3 correct answers were labeled as having limited cancer health literacy, whereas those who provided between 4 and 6 correct answers were labeled as having adequate cancer health literacy. We then adopted logistic regression to analyze the factors that were closely related to limited cancer health literacy among at-risk study participants. RESULTS: The logistic regression analysis identified the following factors that effectively predicted limited cancer health literacy: (1) male gender, (2) low education attainment, (3) age, (4) high levels of self-assessed general disease knowledge, (5) low levels of digital health literacy, (6) limited communicative health literacy, (7) low general health numeracy, and (8) high levels of mistrust in health authorities. CONCLUSIONS: Using regression analysis, we successfully identified 8 factors that could be used as predictors of limited cancer health literacy among Chinese populations. These findings have important clinical implications for supporting Chinese people with limited cancer health literacy through the development of more targeted health educational programs and resources that better align with their actual skill levels.

Using the Multidimensional Health Locus of Control Scale Form C to Investigate Health Beliefs About Bladder Cancer Prevention and Treatment Among Male Patients: Cross-Sectional Study.

BACKGROUND: Bladder cancer is a leading cause of death among Chinese male populations in recent years. The health locus of control construct can mediate health status and outcomes, and it has proven helpful in predicting and explaining specific health-related behaviors. However, it has never been used to investigate health beliefs about bladder cancer prevention and treatment. OBJECTIVE: This study aimed to classify male patients into different latent groups according to their beliefs about bladder cancer prevention and treatment and to identify associated factors to provide implications for the delivery of tailored education and interventions and the administration of targeted prevention and treatment. METHODS: First, we designed a four-section questionnaire to solicit data: section 1-age, gender, and education; section 2-the communicative subscale of the All Aspects of Health Literacy Scale; section 3-the eHealth Literacy Scale; and section 4-health beliefs about bladder cancer prevention and treatment measured by the Multidimensional Health Locus of Control Scale Form C. We hypothesized that the participants' health beliefs about bladder cancer prevention and treatment measured in section 4 could be closely associated with information collected through sections 1 to 3. We recruited 718 Chinese male patients from Qilu Hospital of Shandong University, China, and invited them to participate in a web-based questionnaire survey. Finally, we used latent class analysis to identify subgroups of men based on their categorical responses to the items on the Multidimensional Health Locus of Control Scale Form C and ascertained factors contributing to the low self-efficacy group identified. RESULTS: We identified 2 subgroups defined as low and moderate self-efficacy groups representing 75.8% (544/718) and 24.2% (174/718) of the total sample, respectively. Men in the low self-efficacy cluster (cluster 1: 544/718, 75.8%) were less likely to believe in their own capability or doctors' advice to achieve optimal outcomes in bladder cancer prevention and treatment. Men in the moderate self-efficacy cluster (cluster 2: 174/718, 24.2%) had distinct psychological traits. They had stronger beliefs in their own capability to manage their health with regard to bladder cancer prevention and treatment and moderate to high levels of trust in health and medical professionals and their advice to achieve better prevention and treatment outcomes. Four factors contributing to low self-efficacy were identified, including limited education (Year 6 to Year 12), aged ≥44 years, limited communicative health literacy, and limited digital health literacy. CONCLUSIONS: This was the first study investigating beliefs about bladder cancer prevention and treatment among Chinese male patients. Given that bladder cancer represents a leading cause of death among Chinese male populations in recent years, the low self-efficacy cluster and associated contributing factors identified in this study can provide implications for clinical practice, health education, medical research, and health policy-making.

The Simplified Chinese Version of the Suitability Assessment of Materials for the Evaluation of Health-Related Information for Adults: Translation and Validation Study.

BACKGROUND: Suitable health education materials can educate people about the potential harms of high-risk factors, leading to expected behavior changes and improved health outcomes. However, most patient education materials were not suitable in terms of content, structure, design, composition, and language, as stated in the literature. There is a pressing need to use well-designed scales to assess the suitability of health education materials. Although such assessment is a common practice in English-speaking communities, few assessment tools are available in mainland China. OBJECTIVE: This study aimed to translate the Suitability Assessment of Materials (SAM) for the evaluation of health-related information for adults into a simplified Chinese version (S-C-SAM) and validate its reliability for evaluating the suitability of health education materials written in simplified Chinese in mainland China. METHODS: The SAM was translated into an S-C-SAM in three steps: (1) translating the SAM into an S-C-SAM, (2) translating the S-C-SAM back into an English version, and (3) testing the translation equivalence between the 2 English versions (original and back-translated) of the SAM linguistically and culturally. Any differences between these 2 English versions were resolved through a panel discussion. The validity of the S-C-SAM was determined by measuring its content validity index. The final version of the S-C-SAM was used by 3 native Chinese-speaking health educators to assess 15 air pollution-related health education materials. The Cohen κ coefficient and Cronbach α were calculated to determine the interrater agreement and internal consistency of the S-C-SAM. RESULTS: We agreed on the final version of the S-C-SAM after settling the discrepancies between the 2 English versions (original and back-translated) and revising 2 items (sentences) rated negatively in content validation. The S-C-SAM was proven valid and reliable: the content validity index was 0.95 both in clarity and in relevance, the Cohen κ coefficient for the interrater agreement was 0.61 (P<.05), and Cronbach α for the internal consistency of the whole scale was .71. CONCLUSIONS: The S-C-SAM is the first simplified Chinese version of the SAM. It has been proven valid and reliable for evaluating the suitability of air pollution-related health education materials written in simplified Chinese in mainland China. It has the potential to be used for assessing the suitability of health education materials specifically selected for other health education purposes.

Functional Health Literacy Among Chinese Populations and Associated Factors: Latent Class Analysis.

BACKGROUND: Poor functional health literacy has been found to be independently associated with poor self-assessed health, poor understanding of one's health condition and its management, and higher use of health services. Given the importance of functional health literacy, it is necessary to assess the overall status of functional health literacy in the general public. However, the literature review shows that no studies of functional health literacy have been conducted among the Chinese population in China. OBJECTIVE: This study aimed to classify Chinese populations into different functional health literacy clusters and ascertain significant factors closely associated with low functional health literacy to provide some implications for health education, medical research, and public health policy making. METHODS: We hypothesized that the participants' functional health literacy levels were associated with various demographic characteristics. Therefore, we designed a four-section questionnaire including the following information: (1) age, gender, and education; (2) self-assessed disease knowledge; (3) 3 validated health literacy assessment tools (ie, the All Aspects of Health Literacy Scale, the eHealth Literacy Scale, and the 6-item General Health Numeracy Test); and (4) health beliefs and self-confidence measured by the Multidimensional Health Locus of Control Scales Form B. Using randomized sampling, we recruited survey participants from Qilu Hospital affiliated to Shandong University, China. The questionnaire was administered via wenjuanxing. A returned questionnaire was valid only when all question items included were answered, according to our predefined validation criterion. All valid data were coded according to the predefined coding schemes of Likert scales with different point (score) ranges. Finally, we used latent class analysis to classify Chinese populations into clusters of different functional health literacy and identify significant factors closely associated with low functional health literacy. RESULTS: All data in the 800 returned questionnaires proved valid according to the predefined validation criterion. Applying latent class analysis, we classified Chinese populations into low (n=292, 36.5%), moderate-to-adequate (n=286, 35.7%), and low-to-moderate (n=222, 27.8%) functional health literacy groups and identified five factors associated with low communicative health literacy: (1) male gender (aged 40-49 years), (2) lower educational attainment (below diploma), (3) age between 38 and 68 years, (4) lower self-efficacy, and (5) belief that staying healthy was a matter of luck. CONCLUSIONS: We classified Chinese populations into 3 functional health literacy groups and identified 5 factors associated with low functional health literacy. These associated factors can provide some implications for health education, medical research, and health policy making.

Susceptibility to Breast Cancer Misinformation Among Chinese Patients: Cross-sectional Study.

BACKGROUND: Currently, breast cancer is the most commonly diagnosed cancer and the sixth-leading cause of cancer-related deaths among Chinese women. Worse still, misinformation contributes to the aggravation of the breast cancer burden in China. There is a pressing need to investigate the susceptibility to breast cancer misinformation among Chinese patients. However, no study has been performed in this respect. OBJECTIVE: This study aims to ascertain whether some demographics (age, gender, and education), some health literacy skills, and the internal locus of control are significantly associated with the susceptibility to misinformation about all types of breast cancers among randomly sampled Chinese patients of both genders in order to provide insightful implications for clinical practice, health education, medical research, and health policy making. METHODS: We first designed a questionnaire comprising 4 sections of information: age, gender, and education (section 1); self-assessed disease knowledge (section 2); the All Aspects of Health Literacy Scale (AAHLS), the eHealth Literacy Scale (eHEALS), the 6-item General Health Numeracy Test (GHNT-6), and the "Internal" subscale of the Multidimensional Health Locus of Control (MHLC) scales (section 3); and 10 breast cancer myths collected from some officially registered and authenticated websites (section 4). Subsequently, we recruited patients from Qilu Hospital of Shandong University, China, using randomized sampling. The questionnaire was administered via wenjuanxing, the most popular online survey platform in China. The collected data were manipulated in a Microsoft Excel file. We manually checked the validity of each questionnaire using the predefined validity criterion. After that, we coded all valid questionnaires according to the predefined coding scheme, based on Likert scales of different point (score) ranges for different sections of the questionnaire. In the subsequent step, we calculated the sums of the subsections of the AAHLS and the sums of the 2 health literacy scales (the eHEALS and GHNT-6) and the 10 breast cancer myths. Finally, we applied logistic regression modeling to relate the scores in section 4 to the scores in sections 1-3 of the questionnaire to identify what significantly contributes to the susceptibility to breast cancer misinformation among Chinese patients. RESULTS: All 447 questionnaires collected were valid according to the validity criterion. The participants were aged 38.29 (SD 11.52) years on average. The mean score for their education was 3.68 (SD 1.46), implying that their average educational attainment was between year 12 and a diploma (junior college). Of the 447 participants, 348 (77.85%) were women. The mean score for their self-assessed disease knowledge was 2.50 (SD 0.92), indicating that their self-assessed disease knowledge status was between "knowing a lot" and "knowing some." The mean scores of the subconstructs in the AAHLS were 6.22 (SD 1.34) for functional health literacy, 5.22 (SD 1.54) for communicative health literacy, and 11.19 (SD 1.99) for critical health literacy. The mean score for eHealth literacy was 24.21 (SD 5.49). The mean score for the 6 questions in the GHNT-6 was 1.57 (SD 0.49), 1.21 (SD 0.41), 1.24 (SD 0.43), 1.90 (SD 0.30), 1.82 (SD 0.39), and 1.73 (SD 0.44), respectively. The mean score for the patients' health beliefs and self-confidence was 21.19 (SD 5.63). The mean score for their response to each myth ranged from 1.24 (SD 0.43) to 1.67 (SD 0.47), and the mean score for responses to the 10 myths was 14.03 (SD 1.78). Through interpreting these descriptive statistics, we found that Chinese female patients' limited ability to rebut breast cancer misinformation is mainly attributed to 5 factors: (1) lower communicative health literacy, (2) certainty about self-assessed eHealth literacy skills, (3) lower general health numeracy, (4) positive self-assessment of general disease knowledge, and (5) more negative health beliefs and lower levels of self-confidence. CONCLUSIONS: Drawing on logistic regression modeling, we studied the susceptibility to breast cancer misinformation among Chinese patients. The predicting factors of the susceptibility to breast cancer misinformation identified in this study can provide insightful implications for clinical practice, health education, medical research, and health policy making.

Factors Associated With Limited Digital Health Literacy Among Chinese Male Populations: Cross-sectional Study.

BACKGROUND: eHealth resources and interventions promise to promote favorable behavior change, self-efficacy, and knowledge acquisition, thereby improving health literacy. However, individuals with limited eHealth literacy may find it difficult to identify, understand, and benefit from eHealth use. It is necessary to identify the self-assessed eHealth literacy of those who use eHealth resources to classify their eHealth literacy levels and to determine the demographic characteristics associated with higher and lower eHealth literacy skills. OBJECTIVE: This study aimed to identify notable factors closely associated with limited eHealth literacy among Chinese male populations to provide some implications for clinical practice, health education, medical research, and public health policy making. METHODS: We hypothesized that participants' eHealth literacy status was associated with various demographic characteristics. Therefore, we elicited the following information in the questionnaire: age and education, self-assessed disease knowledge, 3 well-developed health literacy assessment tools (ie, the All Aspects of Health Literacy Scale, eHealth Literacy Scale, and General Health Numeracy Test), and the 6 Internal items on health beliefs and self-confidence in the Multidimensional Health Locus of Control Scales. Using randomized sampling, we recruited survey participants from Qilu Hospital of Shandong University, China. After validating the data collected through a web-based questionnaire survey via wenjuanxing, we coded all valid data according to predefined coding schemes of Likert scales with different point (score) ranges. We then calculated the total scores of the subsections of the scales or the entire scale. Finally, we used logistic regression modeling to associate the scores of the eHealth Literacy Scale with the scores of the All Aspects of Health Literacy Scale, the General Health Numeracy Test-6, and age and education to ascertain factors considerably associated with limited eHealth literacy among Chinese male populations. RESULTS: All data from the 543 returned questionnaires were valid according to the validation criteria. By interpreting these descriptive statistics, we found that 4 factors were significantly correlated with participants' limited eHealth literacy: older age, lower education attainment, lower levels of all aspects of health literacy (functional, communicative, and critical), and weaker beliefs and self-confidence in internal drivers and strengths to stay healthy. CONCLUSIONS: By applying logistic regression modeling, we ascertained 4 factors that were significantly correlated with limited eHealth literacy among Chinese male populations. These relevant factors identified can inform stakeholders engaging in clinical practice, health education, medical research, and health policy making.

The Value of H2BC12 for Predicting Poor Survival Outcomes in Patients With WHO Grade II and III Gliomas.

Purpose: Glioma is a common primary malignant brain tumor. Grade II (GII) gliomas are prone to develop into anaplastic grade III (GIII) gliomas, which indicate a higher malignancy and poorer survival outcome. This study aimed to satisfy the increasing demand for novel sensitive biomarkers and potential therapeutic targets in the treatment of GII and GIII gliomas. Methods: A TCGA dataset was used to investigate the expression of H2BC12 mRNA in GII and GIII gliomas and its relation to clinical pathologic characteristics. Glioma tissues were collected to verify results from the TCGA dataset, and H2BC12 mRNA was detected by RT-qPCR. ROC analysis was employed to evaluate the classification power for GII and GIII. The significance of H2BC12 mRNA GII and GIII gliomas was also investigated. In addition, H2BC12 expression-related pathways were enriched by gene set enrichment analysis (GSEA). DNA methylation level and mutation of H2BC12 were analyzed by the UALCAN and CBioPortal databases, respectively. Results: Based on the sample data from multiple databases and RT-qPCR, higher expression of H2BC12 mRNA was found in GII and GIII glioma tissue compared to normal tissue, which was consistent with a trend with our clinical specimen. H2BC12 mRNA had a better power in distinguishing between GII and GIII and yielded an AUC of 0.706 with a sensitivity of 76.9% and specificity of 81.8%. Meanwhile, high H2BC12 levels were associated with IDH status, 1p/19q codeletion, primary therapy outcome, and the histological type of gliomas. Moreover, the overall survival (OS), disease-specific survival (DSS), and progress-free interval (PFI) of GII glioma patients with higher levels of H2BC12 were shorter than those of patients with lower levels as well as GIII patients. In the multivariate analysis, a high H2BC12 level was an independent predictor for poor survival outcomes of gliomas. The Wnt or PI3K-AKT signaling pathways, DNA repair, cellular senescence, and DNA double-strand break repair were differentially activated in phenotypes that were positively associated with H2BC12. H2BC12 DNA methylation was high in TP53 nonmutant patients, and no H2BC12 mutation was observed in gliomas patients. Conclusion: H2BC12 is a promising biomarker for the diagnosis and prognosis of patients with WHO grade II and III gliomas.

Genetic features of TP53 mutation and its downstream FOXA1 in prostate cancer.

Metastasis is the most lethal form of prostate cancer, and finding new therapeutic targets remains a major clinical challenge. TP53 mutation has been identified to be involved in tumor progression and metastasis. Nevertheless, direct evidence of the role of TP53 mutation in prostate cancer metastasis and its underlying mechanism remain obscure. Herein, TP53 was found to be the most mutated gene in prostate cancer, and missense mutations were the primary mutation type based on bioinformatics data analysis. Subsequently, TP53 rs12947788 mutation site was significant in prostate cancer, and correlated with metastasis and tumor-node-metastasis (TNM) stage. Furthermore, forkhead box A1 (FOXA1), a target of TP53, was highly expressed in prostate cancer tissue, especially in TP53-mutant patients. It was also associated with patients' Gleason scores and nodal metastasis. Knockdown of FOXA1 suppressed the migration in prostate cancer cells in vitro. Our findings indicate that targeting TP53 mutation and FOXA1 might be a promising therapeutic target for prostate cancer metastasis.

Upregulation of AQP2 mediated by transcription factor FOXO1 inhibits TGF-ß-induced fibrosis in human urothelial cells.

Bladder outlet obstruction (BOO) is a common urological disease, and inhibition of TGF-ß-induced bladder tissue fibrosis may serve as an alternative strategy for BOO treatment. Aquaporin (AQP)2 was reported to be aberrantly expressed in rat BOO, but its specific role was not clarified. The aim of the present study was to explore the role of AQP2 in TGF-ß-induced urothelial cell fibrosis and elucidate the potential underlying mechanism. The SV-HUC-1 human urinary tract epithelial cell line was treated with TGF-ß1 to establish an in vitro model of bladder fibrosis. Cell Counting Kit-8 and wound healing assays were performed to measure cell viability and migration, respectively. Cell transfection was conducted to silence/overexpress AQP2 and Forkhead box O1 (FOXO1). Protein expression was measured using western blotting. Luciferase reporter and chromatin immunoprecipitation assays were used to verify the predicted interaction between AQP2 and FOXO1. The present study found that AQP2 expression was downregulated in TGF-ß1-treated urothelial cells. Overexpression of AQP2 significantly suppressed cell viability, migration and epithelial-to-mesenchymal transition in TGF-ß1-treated SV-HUC-1 cells. In addition, FOXO1 overexpression exerted similar effects as AQP2 overexpression on TGF-ß-treated SV-HUC-1 cells, but these changes were partially abolished by AQP2 knockdown. It was also found that FOXO1 was able to bind to the AQP2 promoter and regulate AQP2 expression. In conclusion, the transcription factor FOXO1 may upregulate AQP2 expression, thereby inhibiting TGF-ß-induced fibrosis in human urothelial cells. The findings of the present study may provide a novel potential strategy for the clinical treatment of BOO by targeting AQP2.

Hypoxia-induced microRNA-155 overexpression in extracellular vesicles promotes renal cell carcinoma progression by targeting FOXO3.

Renal cell carcinoma (RCC) is a form of cancer arising from the renal epithelium, with high mortality rates that have reached stable levels over the past decade. The tumor microenvironment is an essential regulator of tumor progression and survival, and extracellular vesicles (EVs) are an important facet of this microenvironment. Herein, we explored the impact of hypoxia-induced miR-155 expression in EVs on FOXO3 expression in RCC cells and their associated oncogenic activity. We found that RCC patients exhibited elevated miR-155 expression in EVs relative to healthy controls, suggesting that this miRNA may be important in the context of RCC progression. We then characterized EVs produced from RCC cell lines (Caki-1 and 786-O) under normoxic and hypoxic conditions, revealing that hypoxia-induced EVs contained higher levels of miR-155 and promoted cell proliferation. Then, we identified FOXO3 as a miR-155 target. Lastly, hypoxia-induced EVs were found to be able to significantly inhibit FOXO3 activation via facilitating miR-155 up-regulation. Together, these findings indicate that hypoxia can promote the upregulation of miR-155 in EVs and that this miRNA can act in RCC cells to suppress FOXO3 expression, thereby enhancing cellular tumor progression.

LINC01106 post-transcriptionally regulates ELK3 and HOXD8 to promote bladder cancer progression.

Bladder cancer (BCa) is a kind of common urogenital malignancy worldwide. Emerging evidence indicated that long noncoding RNAs (lncRNAs) play critical roles in the progression of BCa. In this study, we discovered a novel lncRNA LINC01116 whose expression increased with stages in BCa patients and closely related to the survival rate of BCa patients. However, the molecular mechanism dictating the role of LINC01116 in BCa has not been well elucidated so far. In our study, we detected that the expression of LINC01116 was boosted in BCa cells. Moreover, the results of a series of functional assays showed that LINC01116 knockdown suppressed the proliferation, migration, and invasion of BCa cells. Thereafter, GEPIA indicated the closest correlation of LINC01116 with two protein-coding genes, ELK3 and HOXD8. Interestingly, LINC01116 was mainly a cytoplasmic lncRNA in BCa cells, and it could modulate ELK3 and HOXD8 at post-transcriptional level. Mechanically, LINC01116 increased the expression of ELK3 by adsorbing miR-3612, and also stabilized HOXD8 mRNA by binding with DKC1. Rescue experiments further demonstrated that the restraining influence of LINC01116 knockdown on the progression of BCa, was partly rescued by ELK3 promotion, but absolutely reversed by the co-enhancement of ELK3 and HOXD8. More intriguingly, HOXD8 acted as a transcription factor to activate LINC01116 in BCa. In conclusion, HOXD8-enhanced LINC01116 contributes to the progression of BCa via targeting ELK3 and HOXD8, which might provide new targets for treating patients with BCa.

Somatostatin Derivate (smsDX) Attenuates the TAM-Stimulated Proliferation, Migration and Invasion of Prostate Cancer via NF-κB Regulation.

Tumor development and progression are influenced by macrophages of the surrounding microenvironment. To investigate the influences of an inflammatory tumor microenvironment on the growth and metastasis of prostate cancer, the present study used a co-culture model of prostate cancer (PCa) cells with tumor-associated macrophage (TAM)-conditioned medium (MCM). MCM promoted PCa cell (LNCaP, DU145 and PC-3) growth, and a xenograft model in nude mice consistently demonstrated that MCM could promote tumor growth. MCM also stimulated migration and invasion in vitro. Somatostatin derivate (smsDX) significantly attenuated the TAM-stimulated proliferation, migration and invasion of prostate cancer. Immunohistochemistry revealed that NF-κB was over-expressed in PCa and BPH with chronic inflammatory tissue specimens and was positively correlated with macrophage infiltration. Further investigation into the underlying mechanism revealed that NF-κB played an important role in macrophage infiltration. SmsDX inhibited the paracrine loop between TAM and PCa cells and may represent a potential therapeutic agent for PCa.

Nitidine chloride induces apoptosis and inhibits tumor cell proliferation via suppressing ERK signaling pathway in renal cancer.

Nitidine chloride (NC), a natural bioactive alkaloid derived from Zanthoxylum nitidum (Roxb) DC, has been shown to have inhibitory effects on various tumors. However, whether NC could exert anti-cancer activity and the underlying mechanisms have not been elucidated in renal cancer cells. In this study, we demonstrated the growth inhibitory and pro-apoptotic effects of NC on renal cancer cells both in vitro and in vivo. With cell viability and flow cytometric apoptosis assays, we found that NC potently suppressed the growth of 786-O and A498 cells in a time- and dose- dependent manner. Consistently, the xenograft model performed in nude mice exhibited reduced tumor growth with NC treatment. Mechanically, we presented that NC significantly decreased phosphorylation of ERK and Akt, accompanied by up-regulation of P53, Bax, cleavage caspase-3 and cleavage PARP, downregulation of Bcl-2, caspase-3 and PARP. Furthermore, a specific MEK inhibitor, PD98059, could potentiate the pro-apoptotic effects of NC, which indicated that NC might trigger apoptosis in renal cancer cells partly via inhibition of ERK activity. Taken together, our results imply that NC could be developed as a potential anticancer agent to renal cancer and worthy of further studies.

Somatostatin derivative (smsDX) targets cellular metabolism in prostate cancer cells after androgen deprivation therapy.

Cancer cell metabolism responsive to androgen deprivation therapy (ADT) may be involved in the development and progression of prostate cancer and the ultimate failure of androgen-deprivation therapy. To investigate the metabolism regulation effects on androgen-independent growth of prostate cancer, an established LNCaP-s cell model that resembles the clinical scenario of castration-resistant prostate cancer (CRPC), was used in this current study. This cell line was cultured from androgen-sensitive LNCaP parental cells, in an androgen-reduced condition, resembling clinical androgen deprivation therapy. To assess the effects of smsDX on the invasiveness of prostate cancer cells we used wound healing assay and Matrigel™ invasion assay. We evaluated differentially expressed proteins of the parental LNCaP cells and LNCaP-s cells after ADT by means of two-dimensional gel electrophoresis (2-DE) followed by MALDI-TOF mass spectrometric analysis. The covered area in the wound and the number of cells invading through a Matrigel chamber were significantly smaller for cells treated with smsDX than they were for control cells treated with vehicle. 56 proteins were found differentially expressed in LNCaP-s cells compared to LNCaP cells, majority of them were down-regulated after ADT treatment. 104 proteins of LNCaP cells and 86 in LNCaP-s cells, separately, were found differentially expressed after treatment with smsDX, When we explored these protein functions within the website UniProtKB/Swiss-Prot, surprisingly, most of the proteins were found to be involved in the cellular metabolism and mitochondrial function regulation. LNCaP-s as potential metastatic androgen-independent cancer cells, its metabolism and mitochondrial functions could be altered by a new somatostatin derivative smsDX, the smsDX regulatory effects on metabolism in LNCaP-s deliver more therapeutic information with the treatment of CRPC.

Simvastatin inhibits renal cancer cell growth and metastasis via AKT/mTOR, ERK and JAK2/STAT3 pathway.

Renal cell carcinoma (RCC) is the most lethal type of genitourinary cancer due to its occult onset and resistance to chemotherapy and radiation. Recently, accumulating evidence has suggested stains, inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, were associated with the risk reduction of cancer. In the present study, we aimed to investigate the potential effects of simvastatin on RCC cells and the underlying mechanisms by which simvastatin exerted its actions. With cell viability, colony formation, and flow cytometric apoptosis assays, we found that simvastatin potently suppressed cell growth of A498 and 786-O cells in a time- and dose- dependent manner. Consistently, the xenograft model performed in nude mice exhibited reduced tumor growth with simvastatin treatment. In addition, the inhibitory effects of simvastatin on migration and invasion were also observed in vitro. Mechanically, we presented that simvastatin could suppress the proliferation and motility of RCC cells via inhibiting the phosphorylation of AKT, mTOR, and ERK in a time- and dose- dependent manner. Further investigation of the underlying mechanism revealed simvastatin could exert the anti-tumor effects by suppressing IL-6-induced phosphorylation of JAK2 and STAT3. In conclusion, these findings suggested that simvastatin-induced apoptosis and its anti-metastasis activity in RCC cells were accompanied by inhibition of AKT/mTOR, ERK, and JAK2/STAT3 pathways, which imply that simvastatin may be a potential therapeutic agent for the treatment of RCC patients.