CLCA1 is Poorly Expressed in Stomach Adenocarcinoma and Correlates with Immune Infiltration / CLCA1 se Expresa Deficientemente en el Adenocarcinoma de Estómago y se Correlaciona con la Infiltración Inmune

SUMMARY: Calcium-activated chloride channel regulator 1 (CLCA1) is associated with cancer progression. The expression and immunologic function of CLCA1 in stomach adenocarcinoma (STAD) remain unclear. In this investigation, the expression of CLCA1 in STAD tissues and its involvement in the progression and immune response of STAD were examined using databases such as cBioPortal, TISIDB, and UALCAN. In order to validate the expression level of CLCA1 protein in gastric adenocarcinoma, thirty clinical tissue specimens were gathered for immunohistochemical staining. The findings indicated a downregulation of CLCA1 in STAD patients, which was correlated with race, age, cancer grade, Helicobacter pylori infection, and molecular subtype. Through the examination of survival analysis, it was identified that diminished levels of CLCA1 within gastric cancer cases were linked to decreased periods of post-progression survival (PPS), overall survival (OS), and first progression (FP) (P<0.05). The CLCA1 mutation rate was lower in STAD, but the survival rate was higher in the variant group. The correlation between the expression level of CLCA1 and the levels of immune infiltrating cells in STAD, as well as the immune activating molecules, immunosuppressive molecules, MHC molecules, chemokines, and their receptor molecules, was observed. Gene enrichment analysis revealed that CLCA1 may be involved in STAD progression through systemic lupus erythematosus (SLE), proteasome, cell cycle, pancreatic secretion, and PPAR signaling pathways. In summary, CLCA1 is anticipated to function as a prognostic marker for patients with STAD and is linked to the immunization of STAD.

El regulador 1 del canal de cloruro activado por calcio (CLCA1) está asociado con la progresión del cáncer. La expresión y la función inmunológica de CLCA1 en el adenocarcinoma de estómago (STAD) aún no están claras. En esta investigación, se examinó la expresión de CLCA1 en tejidos STAD y su participación en la progresión y respuesta inmune de STAD utilizando bases de datos como cBioPortal, TISIDB y UALCAN. Para validar el nivel de expresión de la proteína CLCA1 en el adenocarcinoma gástrico, se recolectaron treinta muestras de tejido clínico para tinción inmunohistoquímica. Los hallazgos indicaron una regulación negativa de CLCA1 en pacientes con STAD, que se correlacionó con la raza, la edad, el grado del cáncer, la infección por Helicobacter pylori y el subtipo molecular. Mediante el examen del análisis de supervivencia, se identificó que los niveles reducidos de CLCA1 en los casos de cáncer gástrico estaban relacionados con períodos reducidos de supervivencia posterior a la progresión (PPS), supervivencia general (OS) y primera progresión (FP) (P <0,05). La tasa de mutación CLCA1 fue menor en STAD, pero la tasa de supervivencia fue mayor en el grupo variante. Se observó la correlación entre el nivel de expresión de CLCA1 y los niveles de células inmunes infiltrantes en STAD, así como las moléculas activadoras inmunes, moléculas inmunosupresoras, moléculas MHC, quimiocinas y sus moléculas receptoras. El análisis de enriquecimiento genético reveló que CLCA1 puede estar involucrado en la progresión de STAD a través del lupus eritematoso sistémico (LES), el proteasoma, el ciclo celular, la secreción pancreática y las vías de señalización de PPAR. En resumen, se prevé que CLCA1 funcione como un marcador de pronóstico para pacientes con STAD y está vinculado a la inmunización de STAD.

Comprehensive Analysis of CLCA1 Expression, Immune Infiltration and Immune Checkpoints in Colon Adenocarcinoma / Análisis Completo de la Expresión de CLCA1, Infiltración Inmune y Puntos de Control Inmunológico en Colonadenocarcinoma

SUMMARY: Colon adenocarcinoma (COAD) is a prevalent disease worldwide, known for its high mortality and morbidity rates. Despite this, the extent of investigation concerning the correlation between COAD's CLCA1 expression and immune cell infiltration remains insufficient. This study seeks to examine the expression and prognosis of CLCA1 in COAD, along with its relationship to the tumor immune microenvironment. These findings will offer valuable insights for clinical practitioners and contribute to the existing knowledge in the field. In order to evaluate the prognostic significance of CLCA1 in individuals diagnosed with colorectal cancers, we conducted a comprehensive analysis using univariate and multivariate Cox regression models along with receiver operating characteristic curve (ROC) analysis. This study was performed on the patient data of COAD obtained from The Cancer Genome Atlas (TCGA) database. Nomograms were developed to anticipate CLCA1 prognostic influence. Furthermore, the CLCA1 association with tumor immune infiltration, immune checkpoints, immune checkpoint blockade (ICB) response, interaction network, and functional analysis of CLCA1-related genes was analyzed. We found that Colon adenocarcinoma tissues significantly had decreased CLCA1 expression compared to healthy tissues. Furthermore, the study revealed that the group with high expression of CLCA1 demonstrated a significantly higher overall survival rate (OS) as compared to the group with low expression. Multivariate and Univariate Cox regression analysis revealed the potential of CLCA1 as a standalone risk factor for COAD. These results were confirmed using nomograms and ROC curves. In addition, protein-protein interaction (PPI) network analysis and functional gene enrichment showed that CLCA1 may be associated with functional activities such as pancreatic secretion, estrogen signaling and cAMP signaling, as well as with specific immune cell infiltration. Therefor, as a new independent predictor and potential biomarker of COAD, CLCA1 plays a crucial role in the advancement of colon cancer.

El adenocarcinoma de colon (COAD) es una enfermedad prevalente a nivel mundial, conocida por sus altas tasas de mortalidad y morbilidad. Sin embargo, el alcance de la investigación sobre la correlación entre la expresión de CLCA1 de COAD y la infiltración de células inmunes sigue siendo insuficiente. Este estudio busca examinar la expresión y el pronóstico de CLCA1 en COAD, junto con su relación con el microambiente inmunológico del tumor. Estos hallazgos ofrecerán conocimientos valiosos para los profesionales clínicos y contribuirán al conocimiento existente en el campo. Para evaluar la importancia de pronóstico de CLCA1 en personas diagnosticadas con cáncer colorrectal, realizamos un análisis exhaustivo utilizando modelos de regresión de Cox univariados y multivariados junto con un análisis de la curva característica operativa del receptor (ROC). Este estudio se realizó con los datos de pacientes de COAD obtenidos de la base de datos The Cancer Genome Atlas (TCGA). Se desarrollaron nomogramas para anticipar la influencia pronóstica de CLCA1. Además, se analizó la asociación de CLCA1 con la infiltración inmunitaria tumoral, los puntos de control inmunitarios, la respuesta de bloqueo de los puntos de control inmunitarios (ICB), la red de interacción y el análisis funcional de genes relacionados con CLCA1. Descubrimos que los tejidos de adenocarcinoma de colon tenían una expresión significativamente menor de CLCA1 en comparación con los tejidos sanos. Además, el estudio reveló que el grupo con alta expresión de CLCA1 demostró una tasa de supervivencia general (SG) significativamente mayor en comparación con el grupo con baja expresión. El análisis de regresión de Cox multivariado y univariado reveló el potencial de CLCA1 como factor de riesgo independiente de COAD. Estos resultados se confirmaron mediante nomogramas y curvas ROC. Además, el análisis de la red de interacción proteína- proteína (PPI) y el enriquecimiento de genes funcionales mostraron que CLCA1 puede estar asociado con actividades funcionales como la secreción pancreática, la señalización de estrógenos y la señalización de AMPc, así como con la infiltración de células inmunes específicas. Por lo tanto, como nuevo predictor independiente y biomarcador potencial de COAD, CLCA1 desempeña un papel crucial en el avance del cáncer de colon.

Application of SERS in In-Vitro Biomedical Detection.

Surface-enhanced Raman scattering (SERS), as a rapid and nondestructive biological detection method, holds great promise for clinical on spot and early diagnosis. In order to address the challenging demands of on spot detection of biomedical samples, a variety of strategies has been developed. These strategies include substrate structural and component engineering, data processing techniques, as well as combination with other analytical methods. This report summarizes the recent SERS developments for biomedical detection, and their promising applications in cancer detection, virus or bacterial infection detection, miscarriage spotting, neurological disease screening et al. The first part discusses the frequently used SERS substrate component and structures, the second part reports on the detection strategies for nucleic acids, proteins, bacteria, and virus, the third part summarizes their promising applications in clinical detection in a variety of illnesses, and the forth part reports on recent development of SERS in combination with other analytical techniques. The special merits, challenges, and perspectives are discussed in both introduction and conclusion sections.

[Correlation between TOPA2A gene expression and the number of CD4+ T cells in hepatocellular carcinoma and its clinical prognostic significance].

Objective To analyze the correlation between the expression of TOP2A gene and the proportion of CD4+T cells in hepatocellular carcinoma (HCC) and its clinical prognostic significance. Methods The expression of TOP2A mRNA in normal liver tissues and HCC tissues and its significance for survival and prognosis of HCC patients were analyzed by BioGPS, GEPIA and Kaplan-Meier Plotter databases. The coexpression gene of TOP2A and its GO function were analyzed using GENE and Metascape databases, along with the KEGG pathway enrichment analysis. The correlation between TOP2A and microsatellite instability (MSI) and DNA repair gene was analyzed by Sangerbox database. Then, the correlation between TOP2A gene and CD4+ T cells and various immune cells was analyzed by TISIDB and TIMER database, and analysis was also performed regarding the effect of CD4+ T cells on the survival and prognosis of HCC patients. Results TOP2A mRNA is not significantly expressed in normal liver tissues and CD4+ T cells, but is significantly expressed in HCC tissue, which is not conducive to the survival and prognosis of patients. The GO function of TOP2A coexpression gene is mainly enriched in cell mitosis and cell proliferation, while KEGG is mainly enriched in cell cycle and platinum drug resistance pathway. The expression of TOP2A is positively correlated with MSI, MSH2 and MSH6 of DNA repair gene, the purity of tumor cells and the numbers of various immune cells. All kinds of immune cells reported certain copy number variation in HCC, but only the numbers of CD4+ T cells showed a significant effect on the survival and prognosis of HCC patients. Conclusion There is a significant positive correlation between the expression of TOP2A mRNA and the number of CD4+T cells in HCC, which is not conducive to the survival and prognosis of HCC patients.

Topoisomerase â ¡α Gene as a Marker for Prognostic Prediction of Hepatocellular Carcinoma: A Bioinformatics Analysis.

Objective To investigate the expression of topoisomeraseⅡα (TOP2α) in hepatocellular carcinoma (HCC) and its role in predicting prognosis of HCC patients. Methods We used HCC-related datasets in UALCAN, HCCDB, and cBioPortal databases to analyze the expression and mutation of TOP2α and its co-expressed genes in HCC tissues. GO function and KEGG pathway enrichment of TOP2α and its co-expressed genes were identified. The TIMER database was used to analyze infiltration levels of immune cells in HCC. The impacts of TOP2α and its co-expression genes and the infiltrated immune cells on the survival of HCC patients were assayed by Kaplan-Meier plotter analysis. Results TOP2α and its co-expression genes were highly expressed in HCC (P< 0.001) and detrimental to overall survival of HCC patients (P< 0.001). TOP2α and its co-expression genes were mainly involved in cell mitosis and proliferation, and cell cycle pathway (ID: hsa04110, P = 0.001945). TOP2α and its co-expression genes were mutated in HCC and the mutations were significantly detrimental to overall survival (P = 0.0247) and disease-free survival (P = 0.0265) of HCC patients. High TOP2α expression was positively correlated with the infiltration of B cell (r = 0.459, P< 0.01), CD8+ T cell (r = 0.312, P< 0.01), CD4+ T cell (r = 0.370, P< 0.01), macrophage (r = 0.459, P< 0.01), neutrophil (r = 0.405, P< 0.01), and dendritic cell (r = 0.473, P< 0.01) in HCC. The CD8+ T cell infiltration significantly prolonged the 3- and 5-year survival of HCC patients (all P< 0.05), and CD4+ T cell infiltration significantly shortened the 3-, 5-, and 10-year survival of HCC patients (all P< 0.05). ConclusionTOP2α may be an oncogene, which was associated with poor prognosis of HCC patients and could be used as a biomarker for the prognostic prediction of HCC.

[Bioinformatics analysis and significance of expression of CC chemokine ligand 23 (CCL23) in hepatocellular carcinoma].

Objective To investigate the expression of C-C motif chemokine ligand 23 (CCL23) in hepatocellular carcinoma (HCC) and its clinical significance for survival and prognosis. Methods GEPIA, HCCDB, MetaScape, TIMER, TISIDB, Kaplan-Meier Plotter and other online databases were used to analyze the expression level of CCL23 in HCC, the functional notes of co-expression gene and its gene ontology (GO), the enrichment of Kyoto gene and genome encyclopedia (KEGG), the correlation between tumor cell purity, the expression of CCL23 in immune cells and its significance for survival and prognosis of patients. Results The expression of CCL23 in all stages of HCC was negatively correlated with the purity of HCC tumor cells. The short prognosis of HCC patients with low expression of CCL23 was poor. The GO function and KEGG pathway of CCL23 co-expressed gene in HCC were mainly enriched in immune cell activation and complement system activation. CCL23 was the strongest chemokine factor in HCC, and it could bind to multiple receptors including CC chemokine receptor 1 (CCR1), CCR2, CCR7 and CXC chemokine receptor 6 (CXCR6) to exert chemokine effect on immune cells, among which CD8+ T cells and macrophages have the most obvious chemokine effect. Conclusion The low expression of CCL23 in HCC tissue is not conducive to the development of anti-tumor immune defense in HCC patients and significantly shortens the survival of HCC patients.

Response of greenhouse gas emissions and microbial community dynamics to temperature variation during partial nitrification.

This study investigated the greenhouse gas emission characteristics and microbial community dynamics with the variation of temperature during partial nitrification. Low temperature weakened nitrite accumulation, and partial nitrification would shift to complete nitrification easily at 15 °C. Based on CO2 equivalents (CO2-eq), partial nitrification process released 2.7 g of greenhouse gases per gMLSS per cycle, and N2O accounted for more than 98% of the total CO2-eq emission. The total CO2-eq emission amount at 35 °C was 45.6% and 153.4% higher than that at 25 °C and 15 °C, respectively. During partial nitrification, the microbial community diversity greatly declined compared with seed sludge. However, the diversity was enhanced at low temperature. The abundance of Betaproteobacteria at class level increased greatly during partial nitrification. Proteobacteria abundance declined while Nitrospira raised at low temperature. The nosZ community abundance was not affected by temperature, although N2O emission was varied with the operating temperature.