Identification of a seven-lncRNAs panel that serves as a prognosis predictor and contributes to the malignant progression of laryngeal squamous cell carcinoma.

Background: Laryngeal squamous cell carcinoma (LSCC) is one of the most frequent head and neck cancers worldwide. Long non-coding RNAs (lncRNAs) play a critical role in tumorigenesis. However, the clinical significance of lncRNAs in LSCC remains largely unknown. Methods: In this study, transcriptome sequencing was performed on 107 LSCC and paired adjacent normal mucosa (ANM) tissues. Furthermore, RNA expression and clinical data of 111 LSCC samples were obtained from The Cancer Genome Atlas (TCGA) database. Bioinformatics analysis were performed to construct a model for predicting the overall survival (OS) of LSCC patients. Moreover, we investigated the roles of lncRNAs in LSCC cells through loss-of-function experiments. Results: A seven-lncRNAs panel including ENSG00000233397, BARX1-DT, LSAMP-AS1, HOXB-AS4, MNX1-AS1, LINC01385, and LINC02893 was identified. The Kaplan-Meier analysis demonstrated that the seven-lncRNAs panel was significantly associated with OS (HR:6.21 [3.27-11.81], p-value<0.0001), disease-specific survival (DSS) (HR:4.34 [1.83-10.26], p-value=0.0008), and progression-free interval (PFI) (HR:3.78 [1.92-7.43], p-value=0.0001). ROC curves showed the seven-lncRNAs panel predicts OS with good specificity and sensitivity. Separately silencing the seven lncRNAs inhibited the proliferation, migration, and invasion capacity of LSCC cells. Conclusion: Collectively, this seven-lncRNAs panel is a promising signature for predicting the prognosis of LSCC patients, and these lncRNAs could serve as potential targets for LSCC treatment.

[Influence of Land Use and Land Cover Patterns on Water Quality at Different Spatio-temporal Scales in Hehuang Valley].

Based on the measured water quality data of Huangyuan County, Huzhu Tu Autonomous County, and Minhe Hui Tu Autonomous County in Hehuang Valley of Qinghai province in the normal and wet seasons, the effects of land use and land cover patterns on regional seasonal water quality were analyzed using remote sensing technology and mathematical statistics. The results showed that:① the concentrations of total nitrogen and total phosphorus in the surface water of Hehuang Valley were high. Water pollution areas (Class Ⅳ and Ⅴ) were mainly concentrated in the lower reaches of the river and the junction of tributaries. ② The explanation rate of land use to water quality in the normal season was higher than that in the wet season. The optimal scale was the 200 m buffer scale in the normal season, and farmland and towns were the main influencing factors. The optimal scale in the wet season was the 5 km buffer scale, and the main influencing factor was the forest. ③ In the normal season, the proportion of farmland was positively correlated with the concentration of total nitrogen and permanganate index but negatively correlated with the concentration of total phosphorus. The proportion of town area was positively correlated with the water quality index. The proportion of grassland area in the wet season was positively correlated with the permanganate index. The proportion of forestland area was negatively correlated with water quality index in both periods. Farmland, grassland, and town areas were the "source" landscape of pollutants, but farmland also played a role in intercepting pollutants to a certain extent. Forest land was the "sink" landscape of pollutants. ④ The pattern of forestland in the 200 m buffer zone in the normal season had a high explanatory rate for water quality, and the largest patch index (LPI) and patch density (PD) were the main factors. The study showed that it is an important measure to purify the surface water quality of Hehuang Valley by rationally planning the proportion of residential land and cultivated land and improving the coverage rate and aggregation degree of forestland around the riparian zone.

Trewioidesine A, an unsaturated fatty acid from rhizomes of Alchornea trewioides, shows synergy with NGF in inducing differentiation of pheochromocytoma PC12 cells.

A new unsaturated fatty acid trewioidesine A (1), together with seven known compounds (2 - 8) were isolated from the rhizomes of Alchornea trewioides (Benth.) Muell. Arg. Their structures were established on the basis of extensive spectroscopic data interpretation (1 D and 2 D NMR, and HRESIMS). The absolute configuration of 1 was determined by electronic circular dichroism (ECD) calculations, confirming as trewioidesine A. The functionality of isolated compounds was tested in cultured PC12 cells, a cell line from rat pheochromocytoma. Trewioidesine A was the one showing robust activity in inducing neuronal differentiation: the induction was synergized when co-applied with nerve growth factor (NGF). In addition, a neurofilament 200 (NF200) promoter-luciferase (pNF200-Luc) reporter was used to evaluate the differentiating ability in the transfected PC12 cells for the isolated compounds. Trewioidesine A exhibited a strong NF200 promoter activation, and application of trewioidesine A with low dose of NGF significantly induced the promoter activity over 50%.

An original cuproptosis-related genes signature effectively influences the prognosis and immune status of head and neck squamous cell carcinoma.

Background: Recently, a non-apoptotic cell death pathway that is dependent on the presence of copper ions was proposed, named as cuproptosis. Cuproptosis have been found to have a strong association with the clinical progression and prognosis of several cancers. Head and neck squamous cell carcinoma (HNSC) are among the most common malignant tumors, with a 5-year relative survival rate ranging between 40% and 50%. The underlying mechanisms and clinical significance of cuproptosis-related genes (CRGs) in HNSC progression have not been clarified. Methods: In this study, expression pattern, biological functions, Immunohistochemistry (IHC), gene variants and immune status were analyzed to investigate the effects of CRGs on HNSC progression. Moreover, a 12-CRGs signature and nomogram were also constructed for prognosis prediction of HNSC. Results: The results revealed that some CRGs were dysregulated, had somatic mutations, and CNV in HNSC tissues. Among them, ISCA2 was found to be upregulated in HNSC and was strongly correlated with the overall survival (OS) of HNSC patients (HR = 1.13 [1.01-1.26], p-value = 0.0331). Functionally, CRGs was mainly associated with the TCA cycle, cell cycle, iron-sulfur cluster assembly, p53 signaling pathway, chemical carcinogenesis, and carbon metabolism in cancer. A 12-CRGs signature for predicting the OS was constructed which included, CAT, MTFR1L, OXA1L, POLE, NTHL1, DNA2, ATP7B, ISCA2, GLRX5, NDUFA1, and NDUFB2. This signature showed good prediction performance on the OS (HR = 5.3 [3.4-8.2], p-value = 3.4e-13) and disease-specific survival (HR = 6.4 [3.6-11], p-value = 2.4e-10). Furthermore, 12-CRGs signature significantly suppressed the activation of CD4+ T cells and antigen processing and presentation. Finally, a nomogram based on a 12-CRGs signature and clinical features was constructed which showed a significantly adverse effect on OS (HR = 1.061 [1.042-1.081], p-value = 1.6e-10) of HNSC patients. Conclusion: This study reveals the association of CRGs with the progression of HNSC based on multi-omics analysis. The study of CRGs is expected to improve clinical diagnosis, immunotherapeutic responsiveness and prognosis prediction of HNSC.

Increased expression of miR-181d is associated with poor prognosis and tumor progression of gastric cancer.

Aberrant expression of miR-181d has been noted in multiple human cancers, but its role in gastric cancer (GC) remains unclear. The aim of this study was to investigate the expression, clinical significance and functional role of miR-181d in GC. We applied quantitative real-time polymerase chain reaction (qRT-PCR) to quantify the expression of miR-181d in 131 GC tissues, as well as in GC cell lines. The correlation of miR-181d expression with overall survival of GC patients was analyzed using the Kaplan-Meier survival method. Cox regression analysis was conducted to further determine the prognostic value of miR-181d in GC. Cellular functional experiments were carried out to calculate the effect that miR-181d had on GC behaviors. MiR-181d expression was significantly up-regulated in both GC tissues and cells (all P< 0.001), and correlated with TNM stage and lymph node metastasis (all P< 0.05). GC patients in the high miR-181d expression group had shorter survival time than those in the low miR-181d expression group (log-rank P< 0.001). Multivariate Cox regression analysis demonstrated that miR-181d expression and TNM stage were two independent prognostic markers for GC. Overexpression of miR-181d significantly promoted the NCI-N87 and MGC-803 cells proliferation, migration and invasion (all P< 0.05). MiR-181d serves a role as an oncogene in GC by promoting tumor progression. And miR-181d might be a novel predictive marker for the prognosis of GC patients.

Hypomethylated gene NRP1 is co-expressed with PDGFRB and associated with poor overall survival in gastric cancer patients.

Gastric cancer (GC) has been an increasingly serious problem in public health. However, there is still a lack of efficient approach to diagnosis and treatment in time, especially in the field of targeted therapy. Increasing evidences demonstrated that DNA methylation plays an essential role in tumorigenesis and progression of GC. Thus the present study aims to identify DNA methylation-based prognostic biomarkers in GC. Two methylation array datasets (GSE25869 and GSE30601) and RNA-seq based gene profiling dataset (TCGA-STAD) were employed for exploring candidate DNA methylation-based biomarkers. Univariate Cox regression analysis was used to select the most efficient prognostic genes in GC patients. Weighted gene correlation network analysis (WGCNA) was performed to screen the cluster of co-expressed genes. As a result, our data proved that NRP1 was a hypomethylated / upregulated gene in GC tissues, and PDGFRB was strongly co-expressed with it. Both of them were significantly associated with the overall survival of patients. More importantly, high expression levels of NRP1 and PDGFRB were associated with malignant phenotypes in GC patients, including Laurén histological diffuse type and higher histological grade. Patients carrying high expression level of NRP1 and PDGFRB had a nearly two-fold increased death risk than others. In summary, the hypomethylated gene, NRP1, and its co-expressed gene, PDGFRB, were significantly correlated with tumor malignant phenotypes, which might serve as potential prognostic biomarkers for GC patients.

Efficacy and safety of apatinib combined with chemotherapy for the treatment of advanced gastric cancer in the Chinese population: a systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the efficacy and safety of the combination of apatinib targeted therapy and chemotherapy (CT) in the treatment of patients with advanced gastric cancer (GC). MATERIALS AND METHODS: Clinical trials were extracted from PubMed, the Cochrane Library, Web of Science, EMBASE, CNKI, and the Wanfang database. Outcome measures, including therapeutic efficacy, quality of life (QOL), and adverse events, were extracted and evaluated. RESULTS: Nineteen trials, including 1,256 advanced GC patients, were included. The results indicated that, compared with CT alone, the combination of apatinib targeted therapy with CT significantly improved the patients' complete response rate (OR=1.85, 95% CI=1.04-3.28, P=0.04), partial response rate (OR=2.19, 95% CI=1.71-2.80, P<0.00001), overall response (OR=2.57, 95% CI=1.99-3.32, P<0.00001), and disease control rate (OR=3.46, 95% CI=2.57-4.66, P<0.00001). Moreover, the combined therapy exhibited advantages over CT alone in the patients' QOL including the QOL improved rate (OR=1.77, 95% CI=0.94-3.33, P=0.08) and the Karnofsky performance score (OR=1.77, 95% CI=0.94-3.33, P=0.08). The group that received the combined therapy had higher rates of hypertension (OR=5.75, 95% CI=2.22-14.92, P=0.0003), albuminuria (OR=15.42, 95% CI=5.39-44.10, P<0.00001), and hand-foot syndrome (OR=2.09, 95% CI=1.26-3.48, P=0.004), whereas analyses of other adverse events, such as leucopenia, thrombocytopenia, and neutropenia, did not reveal significant differences (P>0.05). CONCLUSION: The combination of apatinib targeted therapy and CT is more effective for GC treatment than CT alone. However, this combined treatment could lead to greater rates of hypertension, albuminuria, and hand-foot syndrome. Therefore, the benefits and risks should be considered before treatment.