ABSTRACT
Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis. KCTD4 expression was found upregulated in metastatic ESCC. High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo. Mechanistically, KCTD4 binds to CLIC1 and disrupts its dimerization, thus increasing intracellular Ca2+ level to enhance NFATc1-dependent fibronectin transcription. KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner, which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback. Furthermore, a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4‒CLIC1 interaction, providing a potential therapeutic strategy. Taken together, our study not only uncovers KCTD4 as a regulator of calcium homeostasis, but also reveals KCTD4/CLIC1-Ca2+-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis. These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.
ABSTRACT
Objective@#To evaluate the reliability and validity of the Chinese version of the Sickness Experience Questionnaire (CESQ) in breast cancer patients, and to provide a scientific basis for caring for female breast cancer patients and reducing the level of stigma.@*Methods@#The English version of CESQ was translated and culturally adjusted. 200 questionnaires were sent out to breast cancer patients in our hospital from May 2017 to August 2018 by convenient sampling method. 190 questionnaires were effectively recovered. Sixty patients were randomly selected and retested after 2 weeks. Reliability and validity was examined by SPSS21.0 and AMOS21.0.@*Results@#The Chinese version of CESQ scale Cronbach α coefficient was 0.819, Guttman′s split-half reliability coefficient was 0.844, the correlation coefficient between each item score was 0.405-0.809, and the correlation coefficient between each item score and CESQ total score was 0.499-0.812 (P <0.05). The test-retest reliability coefficient was 0.898. Four experts rated the Chinese version of CESQ with a content validity index of 0.801 to 1.000, an overall consistency content validity index CVI of 0.804, and an average content validity index of 0.830. Principal component analysis was used to conduct exploratory factor analysis. After the orthogonal rotation of the variance, one common factor was obtained, and the cumulative variance contribution rate was 55.65%. Using AMOS 17.0, the data was subjected to confirmatory factor analysis with a chi-square/degree-of-freedom ratio of 1.20 and a goodness-of-fit index of 0.909. The approximate error root mean square was 0.069, the gauge fit index was 0.957, the relative fit index was 0.944, and the value-added fit index was 0.904. Non-standard fit The index was 0.907, the comparative fit index was 0.911, and the normalized regression coefficient was 0.435-0.668.@*Conclusions@#The Chinese version of CESQ has a good reliability and validity in evaluating the stigma of breast cancer patients. It has application value in evaluating the stigma of breast cancer patients in China.
ABSTRACT
Objective To evaluate the reliability and validity of the Chinese version of the Sickness Experience Questionnaire (CESQ) in breast cancer patients, and to provide a scientific basis for caring for female breast cancer patients and reducing the level of stigma. Methods The English version of CESQ was translated and culturally adjusted. 200 questionnaires were sent out to breast cancer patients in our hospital from May 2017 to August 2018 by convenient sampling method. 190 questionnaires were effectively recovered. Sixty patients were randomly selected and retested after 2 weeks. Reliability and validity was examined by SPSS21.0 and AMOS21.0. Results The Chinese version of CESQ scale Cronbach α coefficient was 0.819, Guttman′s split-half reliability coefficient was 0.844, the correlation coefficient between each item score was 0.405-0.809, and the correlation coefficient between each item score and CESQ total score was 0.499-0.812 (P<0.05). The test-retest reliability coefficient was 0.898. Four experts rated the Chinese version of CESQ with a content validity index of 0.801 to 1.000, an overall consistency content validity index CVI of 0.804, and an average content validity index of 0.830. Principal component analysis was used to conduct exploratory factor analysis. After the orthogonal rotation of the variance, one common factor was obtained, and the cumulative variance contribution rate was 55.65％. Using AMOS 17.0, the data was subjected to confirmatory factor analysis with a chi-square/degree-of-freedom ratio of 1.20 and a goodness-of-fit index of 0.909. The approximate error root mean square was 0.069, the gauge fit index was 0.957, the relative fit index was 0.944, and the value-added fit index was 0.904. Non-standard fit The index was 0.907, the comparative fit index was 0.911, and the normalized regression coefficient was 0.435-0.668. Conclusions The Chinese version of CESQ has a good reliability and validity in evaluating the stigma of breast cancer patients. It has application value in evaluating the stigma of breast cancer patients in China.