Tyrosine Phosphatase PTPRO Deficiency in ERBB2-Positive Breast Cancer Contributes to Poor Prognosis and Lapatinib Resistance

Despite the initial benefit from treating ERBB2-positive breast cancer with tyrosine kinase inhibitor lapatinib, resistance develops inevitably. Since the expression of protein tyrosine phosphatase receptor-type O (PTPRO), a member of the R3 subfamily of receptor protein tyrosine phosphatases (PTPs), is inversely correlated with the aggressiveness of multiple malignancies, we decided to explore the correlation between PTPRO and lapatinib resistance in ERBB2-positive breast cancer. Results of immunohistochemical (IHC) staining and the correlation analysis between the expression levels of PTPRO and the clinicopathological parameters indicate that PTPRO is downregulated in cancer tissues as compared with normal tissues and negatively associated with differentiation, tumor size, tumor depth, as well as the expression of ERBB2 and Ki67. Results from Kaplan–Meier analyses indicate that lower expression of PTPRO is correlated with shorter relapse-free survival for patients with ERBB2-positive breast cancer, and multivariable Cox regression analysis found that PTPRO can potentially serve as an independent prognostic indicator for ERBB2-positive breast cancer. Results from both human breast cancer cells with PTPRO knockdown or overexpression and mouse embryonic fibroblasts (MEFs) which derived from Ptpro ( +/+ ) and Ptpro ( −/− ) mice with then stably transfected plasmid FUGW-Erbb2 consistently demonstrated the essentiality of PTPRO in the lapatinib-mediated anticancer process. Our findings suggest that PTPRO is not only able to serve as an independent prognostic indicator, but upregulating PTPRO can also reverse the lapatinib resistance of ERBB2-positive breast cancer

Salivary extracellular miRNAs for early detection and prognostication of esophageal cancer:a clinical study

BACKGROUND AND AIMS: Early detection of esophageal squamous cell carcinoma (ESCC) will facilitate curative treatment. We aimed to establish a micro-RNA (miRNA) signature derived from salivary extracellular vesicles and particles (EVPs) for early ESCC detection and prognostication.METHODS: Salivary EVP miRNA expression was profiled in a pilot cohort (n=54) using microarray. Area under the receiver-operator characteristic curve (AUROC) and lasso regression analyses were used to prioritize miRNAs that discriminated ESCC patients from controls. Using quantitative reverse transcription-polymerase chain reaction, the candidates were measured in a discovery cohort (n=72) and cell lines. The prediction models for the biomarkers were derived from a training cohort (n=342) and validated in an internal cohort (n=207) and an external cohort (n=226).RESULTS: The microarray analysis identified 7 miRNAs for distinguishing ESCC patients from control subjects. Since one was not always detectable in the discovery cohort and cell lines, the other 6 miRNAs formed a panel. A signature of this panel accurately identified all-stage ESCC patients in the training cohort (AUROC=0.968) and was successfully validated in two independent cohorts. Importantly, this signature could distinguish early-stage (stage Ⅰ/ Ⅱ) ESCC patients from control subjects in the training cohort (AUROC=0.969, sensitivity=92.00%, specificity=89.17%), internal (sensitivity=90.32%, specificity=91.04%) and external (sensitivity=91.07%, specificity=88.06%) validation cohorts. Moreover, a prognostic signature based on the panel was established and efficiently predicted the high-risk cases with poor progression-free survival and overall survival.CONCLUSION: The salivary EVP-based 6-miRNA signature can serve as noninvasive biomarkers for early detection and risk stratification of ESCC. Chinese Clinical Trial Registry, ChiCTR2000031507.</p

Spatial distribution of tuberculosis and its association with meteorological factors in mainland China

BACKGROUND: The incidence of tuberculosis (TB) remains high worldwide. Current strategies will not eradicate TB by 2035; instead, by 2182 is more likely. Therefore, it is urgent that new risk factors be identified. METHODS: An ecological study was conducted in 340 prefectures in China from 2005 to 2015. The spatial distribution of TB incidence was shown by clustering and hotspot analysis. The relationship between the distribution patterns and six meteorological factors was evaluated by the geographically weighted regression (GWR) model. RESULTS: During the 11 years of the study period, TB incidence was persistently low in the east and high in the west. Local coefficients from the GWR model showed a positive correlation between TB incidence and yearly average rainfall (AR) but a negative correlation with other meteorological factors. Average relative humidity (ARH) was negatively correlated with the incidence of TB in all prefectures (p \u3c 0.05). CONCLUSION: Meteorological factors may play an important role in the prevention and control of TB

Salivary extracellular miRNAs for early detection and prognostication of esophageal cancer:a clinical study

BACKGROUND AND AIMS: Early detection of esophageal squamous cell carcinoma (ESCC) will facilitate curative treatment. We aimed to establish a micro-RNA (miRNA) signature derived from salivary extracellular vesicles and particles (EVPs) for early ESCC detection and prognostication.METHODS: Salivary EVP miRNA expression was profiled in a pilot cohort (n=54) using microarray. Area under the receiver-operator characteristic curve (AUROC) and lasso regression analyses were used to prioritize miRNAs that discriminated ESCC patients from controls. Using quantitative reverse transcription-polymerase chain reaction, the candidates were measured in a discovery cohort (n=72) and cell lines. The prediction models for the biomarkers were derived from a training cohort (n=342) and validated in an internal cohort (n=207) and an external cohort (n=226).RESULTS: The microarray analysis identified 7 miRNAs for distinguishing ESCC patients from control subjects. Since one was not always detectable in the discovery cohort and cell lines, the other 6 miRNAs formed a panel. A signature of this panel accurately identified all-stage ESCC patients in the training cohort (AUROC=0.968) and was successfully validated in two independent cohorts. Importantly, this signature could distinguish early-stage (stage Ⅰ/ Ⅱ) ESCC patients from control subjects in the training cohort (AUROC=0.969, sensitivity=92.00%, specificity=89.17%), internal (sensitivity=90.32%, specificity=91.04%) and external (sensitivity=91.07%, specificity=88.06%) validation cohorts. Moreover, a prognostic signature based on the panel was established and efficiently predicted the high-risk cases with poor progression-free survival and overall survival.CONCLUSION: The salivary EVP-based 6-miRNA signature can serve as noninvasive biomarkers for early detection and risk stratification of ESCC. Chinese Clinical Trial Registry, ChiCTR2000031507.</p

Salivary Extracellular MicroRNAs for Early Detection and Prognostication of Esophageal Cancer: A Clinical Study.

BACKGROUND & AIMS: Early detection of esophageal squamous cell carcinoma (ESCC) will facilitate curative treatment. We aimed to establish a microRNA (miRNA) signature derived from salivary extracellular vesicles and particles (EVPs) for early ESCC detection and prognostication. METHODS: Salivary EVP miRNA expression was profiled in a pilot cohort (n = 54) using microarray. Area under the receiver operator characteristic curve (AUROC) and least absolute shrinkage and selector operation regression analyses were used to prioritize miRNAs that discriminated patients with ESCC from controls. Using quantitative reverse transcription polymerase chain reaction, the candidates were measured in a discovery cohort (n = 72) and cell lines. The prediction models for the biomarkers were derived from a training cohort (n = 342) and validated in an internal cohort (n = 207) and an external cohort (n = 226). RESULTS: The microarray analysis identified 7 miRNAs for distinguishing patients with ESCC from control subjects. Because 1 was not always detectable in the discovery cohort and cell lines, the other 6 miRNAs formed a panel. A signature of this panel accurately identified patients with all-stage ESCC in the training cohort (AUROC = 0.968) and was successfully validated in 2 independent cohorts. Importantly, this signature could distinguish patients with early-stage (stage Ⅰ/Ⅱ) ESCC from control subjects in the training cohort (AUROC = 0.969, sensitivity = 92.00%, specificity = 89.17%) and internal (sensitivity = 90.32%, specificity = 91.04%) and external (sensitivity = 91.07%, specificity = 88.06%) validation cohorts. Moreover, a prognostic signature based on the panel was established and efficiently predicted the high-risk cases with poor progression-free survival and overall survival. CONCLUSIONS: The salivary EVP-based 6-miRNA signature can serve as noninvasive biomarkers for early detection and risk stratification of ESCC. Chinese Clinical Trial Registry, ChiCTR2000031507

Salivary extracellular miRNAs for early detection and prognostication of esophageal cancer:a clinical study

BACKGROUND AND AIMS: Early detection of esophageal squamous cell carcinoma (ESCC) will facilitate curative treatment. We aimed to establish a micro-RNA (miRNA) signature derived from salivary extracellular vesicles and particles (EVPs) for early ESCC detection and prognostication.METHODS: Salivary EVP miRNA expression was profiled in a pilot cohort (n=54) using microarray. Area under the receiver-operator characteristic curve (AUROC) and lasso regression analyses were used to prioritize miRNAs that discriminated ESCC patients from controls. Using quantitative reverse transcription-polymerase chain reaction, the candidates were measured in a discovery cohort (n=72) and cell lines. The prediction models for the biomarkers were derived from a training cohort (n=342) and validated in an internal cohort (n=207) and an external cohort (n=226).RESULTS: The microarray analysis identified 7 miRNAs for distinguishing ESCC patients from control subjects. Since one was not always detectable in the discovery cohort and cell lines, the other 6 miRNAs formed a panel. A signature of this panel accurately identified all-stage ESCC patients in the training cohort (AUROC=0.968) and was successfully validated in two independent cohorts. Importantly, this signature could distinguish early-stage (stage Ⅰ/ Ⅱ) ESCC patients from control subjects in the training cohort (AUROC=0.969, sensitivity=92.00%, specificity=89.17%), internal (sensitivity=90.32%, specificity=91.04%) and external (sensitivity=91.07%, specificity=88.06%) validation cohorts. Moreover, a prognostic signature based on the panel was established and efficiently predicted the high-risk cases with poor progression-free survival and overall survival.CONCLUSION: The salivary EVP-based 6-miRNA signature can serve as noninvasive biomarkers for early detection and risk stratification of ESCC. Chinese Clinical Trial Registry, ChiCTR2000031507.</p

Salivary extracellular miRNAs for early detection and prognostication of esophageal cancer:a clinical study

BACKGROUND AND AIMS: Early detection of esophageal squamous cell carcinoma (ESCC) will facilitate curative treatment. We aimed to establish a micro-RNA (miRNA) signature derived from salivary extracellular vesicles and particles (EVPs) for early ESCC detection and prognostication.METHODS: Salivary EVP miRNA expression was profiled in a pilot cohort (n=54) using microarray. Area under the receiver-operator characteristic curve (AUROC) and lasso regression analyses were used to prioritize miRNAs that discriminated ESCC patients from controls. Using quantitative reverse transcription-polymerase chain reaction, the candidates were measured in a discovery cohort (n=72) and cell lines. The prediction models for the biomarkers were derived from a training cohort (n=342) and validated in an internal cohort (n=207) and an external cohort (n=226).RESULTS: The microarray analysis identified 7 miRNAs for distinguishing ESCC patients from control subjects. Since one was not always detectable in the discovery cohort and cell lines, the other 6 miRNAs formed a panel. A signature of this panel accurately identified all-stage ESCC patients in the training cohort (AUROC=0.968) and was successfully validated in two independent cohorts. Importantly, this signature could distinguish early-stage (stage Ⅰ/ Ⅱ) ESCC patients from control subjects in the training cohort (AUROC=0.969, sensitivity=92.00%, specificity=89.17%), internal (sensitivity=90.32%, specificity=91.04%) and external (sensitivity=91.07%, specificity=88.06%) validation cohorts. Moreover, a prognostic signature based on the panel was established and efficiently predicted the high-risk cases with poor progression-free survival and overall survival.CONCLUSION: The salivary EVP-based 6-miRNA signature can serve as noninvasive biomarkers for early detection and risk stratification of ESCC. Chinese Clinical Trial Registry, ChiCTR2000031507.</p

Salivary extracellular miRNAs for early detection and prognostication of esophageal cancer:a clinical study

BACKGROUND AND AIMS: Early detection of esophageal squamous cell carcinoma (ESCC) will facilitate curative treatment. We aimed to establish a micro-RNA (miRNA) signature derived from salivary extracellular vesicles and particles (EVPs) for early ESCC detection and prognostication.METHODS: Salivary EVP miRNA expression was profiled in a pilot cohort (n=54) using microarray. Area under the receiver-operator characteristic curve (AUROC) and lasso regression analyses were used to prioritize miRNAs that discriminated ESCC patients from controls. Using quantitative reverse transcription-polymerase chain reaction, the candidates were measured in a discovery cohort (n=72) and cell lines. The prediction models for the biomarkers were derived from a training cohort (n=342) and validated in an internal cohort (n=207) and an external cohort (n=226).RESULTS: The microarray analysis identified 7 miRNAs for distinguishing ESCC patients from control subjects. Since one was not always detectable in the discovery cohort and cell lines, the other 6 miRNAs formed a panel. A signature of this panel accurately identified all-stage ESCC patients in the training cohort (AUROC=0.968) and was successfully validated in two independent cohorts. Importantly, this signature could distinguish early-stage (stage Ⅰ/ Ⅱ) ESCC patients from control subjects in the training cohort (AUROC=0.969, sensitivity=92.00%, specificity=89.17%), internal (sensitivity=90.32%, specificity=91.04%) and external (sensitivity=91.07%, specificity=88.06%) validation cohorts. Moreover, a prognostic signature based on the panel was established and efficiently predicted the high-risk cases with poor progression-free survival and overall survival.CONCLUSION: The salivary EVP-based 6-miRNA signature can serve as noninvasive biomarkers for early detection and risk stratification of ESCC. Chinese Clinical Trial Registry, ChiCTR2000031507.</p

Salivary extracellular miRNAs for early detection and prognostication of esophageal cancer:a clinical study

BACKGROUND AND AIMS: Early detection of esophageal squamous cell carcinoma (ESCC) will facilitate curative treatment. We aimed to establish a micro-RNA (miRNA) signature derived from salivary extracellular vesicles and particles (EVPs) for early ESCC detection and prognostication.METHODS: Salivary EVP miRNA expression was profiled in a pilot cohort (n=54) using microarray. Area under the receiver-operator characteristic curve (AUROC) and lasso regression analyses were used to prioritize miRNAs that discriminated ESCC patients from controls. Using quantitative reverse transcription-polymerase chain reaction, the candidates were measured in a discovery cohort (n=72) and cell lines. The prediction models for the biomarkers were derived from a training cohort (n=342) and validated in an internal cohort (n=207) and an external cohort (n=226).RESULTS: The microarray analysis identified 7 miRNAs for distinguishing ESCC patients from control subjects. Since one was not always detectable in the discovery cohort and cell lines, the other 6 miRNAs formed a panel. A signature of this panel accurately identified all-stage ESCC patients in the training cohort (AUROC=0.968) and was successfully validated in two independent cohorts. Importantly, this signature could distinguish early-stage (stage Ⅰ/ Ⅱ) ESCC patients from control subjects in the training cohort (AUROC=0.969, sensitivity=92.00%, specificity=89.17%), internal (sensitivity=90.32%, specificity=91.04%) and external (sensitivity=91.07%, specificity=88.06%) validation cohorts. Moreover, a prognostic signature based on the panel was established and efficiently predicted the high-risk cases with poor progression-free survival and overall survival.CONCLUSION: The salivary EVP-based 6-miRNA signature can serve as noninvasive biomarkers for early detection and risk stratification of ESCC. Chinese Clinical Trial Registry, ChiCTR2000031507.</p

Development of attractants and repellents for Tuta absoluta based on plant volatiles from tomato and eggplant

IntroductionTuta absoluta is currently considered one of the most devastating invasive pests of solanaceous plants worldwide, causing severe damage to the tomato industry. Insects use volatile organic compounds (VOCs) to locate host plant for feeding and oviposition. Those VOCs could be developed as lures for pest monitoring and control.MethodsIn this study, the differentially accumulated VOCs between the preferred host (tomato) and non-preferred host (eggplant) were analyzed by GC–MS method, and their roles on female T. absoluta host selection and egg laying behaviors were investigated using electroantennography (EAG), olfactometer and cage experiments.ResultsA total of 39 differentially accumulated VOCs were identified in tomato and eggplant. Strong EAG signals were obtained in 9 VOCs, including 5 VOCs highly accumulated in tomato and 4 VOCs highly accumulated in eggplant. Further olfactometer bioassays showed that 4 compounds (1-nonanol, ethyl heptanoate, ethyl octanoate and o-nitrophenol) were attractive to T. absoluta females, while 5 compounds (2-phenylethanol, 2-pentylfuran, trans,trans-2,4-nonadienal, 2-ethyl-5-methylpyrazine and trans-2-nonenal) were repellent, indicating that VOCs from host plants play important roles in host plant preferences. The attractive activities of 1-nonanol and ethyl octanoate, as well as the repellent activities of trans,trans-2,4-nonadienal and trans-2-nonenal, were further confirmed in cage experiments.DiscussionIn this study, two attractants and two repellents for T. absoluta were developed from plant released VOCs. Our results could be useful to enhance the development of eco-friendly and sustainable pest management strategies for T. absoluta