Identification of SAA1 as a novel metastasis marker in ovarian cancer and development of a graphene-based detection platform for early assessment.

BACKGROUND: Ovarian cancer (OC) is a prevalent gynecological malignancy with the highest mortality rate, which generally diagnosed at late stages due to the lack of effective early screening methods and the nonspecific symptoms. Hence, here we aim to identify new metastasis markers and develop a novel detection method with the characteristics of high sensitivity, rapid detection, high specificity, and low cost when compared with other conventional detection technologies. METHODS: Blood from OC patients with or without metastasis were collected and analyzed by 4D Label free LC - MS/MS. Surgically resect samples from OC patients were collected for Single cell RNA sequencing (sc-RNA seq). Short hairpin RNA (shRNA) was used to silence SAA1 expression in SKOV3 and ID8 to verify the relationship between endogenous SAA1 and tumor invasion or metastasis. The functional graphene chips prepared by covalent binding were used for SAA1 detection. RESULTS: In our study, we identified Serum Amyloid A1 (SAA1) as a hematological marker of OC metastasis by comprehensive analysis of proteins in plasma from OC patients with or without metastasis using 4D Label free LC - MS/MS and gene expression patterns from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Further validation using tumor tissues and plasma from human OC and mouse OC model confirmed the correlation between SAA1 and tumor metastasis. Importantly, sc-RNA seq of human OC samples revealed that SAA1 was specifically expressed in tumor cells and upregulated in the metastasis group. The functional role of SAA1 in metastasis was demonstrated through experiments in vitro and in vivo. Based on these findings, we designed and investigated a graphene-based platform for SAA1 detection to predict the risk of metastasis of OC patients. CONCLUSION: Our study suggests that SAA1 is a biomarker of OC metastasis, and we have developed a rapid and highly sensitive platform using graphene chips to detection of plasma SAA1 for the early assessment of metastasis in OC patients.

Construction and validation of a metabolism-related prognostic model for thyroid cancer.

Metabolic reprogramming is a common pathological process of cancer. Expression of metabolism-related genes differs in thyroid cancer (TC) patients with different prognoses. This work committed to constructing a prognostic model for TC through identifying metabolism-related signatures. Expression profiles of mRNAs and clinical data of TC, were acquired from The Cancer Genome Atlas. Differential analysis was performed on mRNA expression profiles. The obtained differentially expressed genes (DEGs) were overlapped with metabolism-related genes from MSigDB database to acquire metabolism-related DEGs. Cox regression and Least Absolute Shrinkage and Selection Operator analyses were performed to ascertain feature genes and to build a prognostic model for TC. The model was evaluated comprehensively through survival curve, time-dependent receiver operating characteristic (ROC) curve, gene set enrichment analysis (GSEA), and Cox regression analyses combining varying clinical information. 7 key genes related to metabolism, including AWAT2, GGT6, ENTPD1, PAPSS2, CYP26A, ACY3 and PLA2G10, were identified, based on which a prognostic model was constructed. The survival analysis indicated that high-risk group presented shorter survival time than low-risk group. ROC curve results exhibited that AUC values of 3-year and 5-year survival of TC patients were both >0.70. Besides, GSEA on high/low-risk groups revealed that DEGs were mainly gathered in biological functions and signaling pathways linked with keratan sulfate catabolism and triglyceride catabolism. Combined with clinical information, Cox regression analyses unveiled that the 7-gene prognostic model can be an independent predictor. In conclusion, this model can effectively predict prognoses of TC patients, and also offer guidance for clinical treatment of TC.

Identification and validation of a five-gene prognostic signature based on bioinformatics analyses in breast cancer.

Background: This study aimed to identify prognostic signatures to predict the prognosis of breast cancer (BRCA) patients based on a series of comprehensive analyses of gene expression data. Methods: The RNA-sequencing expression data and corresponding BRCA patient clinical data were collected from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) datasets. Firstly, the differently expressed genes (DEGs) related to prognosis between tumor tissues and normal tissues were ascertained by performing R package "limma". Secondly, the DEGs were used to construct a polygenic risk scoring model by the weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator Cox regression (Lasso-cox) analysis method. Thirdly, survival analysis was performed to investigate the risk score values in the TCGA cohort. And the enrichment analysis, immune cell infiltration levels analysis, and protein-protein internet (PPI) analysis were performed. Simultaneously, the GEO cohort was used to validate the model. Lastly, we constructed a nomogram to explore the influence of polygenic risk score and other clinical factors on the survival probability of patients with BRCA. Results: A total of 1000 DEGs including 396 upregulated genes and 604 downregulated genes were identified from the TCGA-BRCA dataset. We obtained 5 prognosis-related genes, as the key biomarkers by Lasso-cox analysis (FBXL19, HAGHL, PHKG2, PKMYT1, and TXNDC17), all of which were significantly upregulated in breast tumors. The prognostic prediction of the 5 genes model was great in training and validation cohorts. Moreover, the high-risk group had a poorer prognosis. The Cox regression analysis showed that the comprehensive risk score for 5 genes was an independent prognosis factor. Conclusion: The 5 genes risk model constructed in this study had an independent predictive ability to distinguish patients with a high risk of death from those with a low-risk score, and it can be used as a practical and reliable prognostic tool for BRCA.

Carbothermal redox reaction in constructing defective carbon as superior oxygen reduction catalysts.

Defects can greatly promote the catalytic activity of a carbon-based electrocatalyst due to charge redistribution of its electroneutral π-conjugated structure. However, it is still a huge challenge to introduce enough defects into carbon-based materials to improve their catalytic activity. Herein, we report a new method for defect generation by the pyrolysis of the sulfur-nitrogen-containing coordination polymer [Zn(ptt)2]n (ptt = 1-phenyl-1H-tetrazole-5-thiol). A series of controlled experiments clearly demonstrates that the carbothermal reduction reaction of zinc sulfide with carbon at a high temperature plays an important role in creating defects and enhancing the catalytic activity for the oxygen reduction reaction (ORR) of the carbon-based materials. The ZnS/C-1100 with a high content of defects and a small number of ZnS nanoparticles exhibits excellent ORR electrocatalytic performances in alkaline media, in which the half-wave potential (0.894 V vs. RHE), stability, and methanol tolerance are all superior to that of a 20 wt% Pt/C catalyst. Moreover, the ZnS/C-1100 driven ZAB (zinc air battery) exhibits a stable discharge at 10 mA, a peak power density of 134 mW cm-2 and a cathode current density of 265 mA cm-2, which are significantly better than that catalyzed by 20 wt% Pt/C under the same conditions. This research not only develops a new highly active catalyst, but also provides a new method for the preparation of defect-rich carbon materials.

[Ba4Cl] Cations Directed Perovskite-like Polar Metal Formate Frameworks {[Ba4Cl][M3(HCO2)13]}n (M = Mn, Co, and Mg): Microwave-Assisted Synthesis, Structures, and Properties.

Novel 3D metal formate frameworks {[Ba4Cl][M3(HCO2)13]}n (M = Mn for 1, Co for 2, and Mg for 3) were successfully assembled via microwave-assisted synthesis. The complexes are rare coordination polymers crystallized at space group P4cc with the polar point group C4v. In the structure, the MII ions are bridged by two types of anti-anti formate in forming a 3D pcu framework, and additional formates coordinate to the unsaturated sites of the MII ions in the framework, giving an anionic M-formate net. Ba4Cl clusters take the cavities of the net as charge balance, in which the chloride ion deviates from the center of the barium ions. The asymmetric Ba4Cl structure is transmitted throughout the crystal resulting in polar structure, which is further confirmed by nonlinear optical and piezoelectric test. Nonlinear optical activity tests of 1 and 3 show SHG signals 0.32 and 0.28 times that of KDP, while 2 has a piezoelectric coefficient d33 of 6.8 pC/N along polar axis. Magnetic studies reveal antiferromagnetic coupling between MII ions in 1 and 2. Spin canting was found only in 2 with anisotropic CoII ions, and 2 is a canted antiferromagnetically with TN = 5 K. Further field-induced spin flop was also found in 2 with a critical field 0.9 T.

Neoadjuvant chemotherapy combined with interval cytoreductive surgery in ovarian cancer.

PURPOSE: This study aimed to explore the value and prognosis-influencing factors for neoadjuvant chemotherapy combined with interval cytoreductive surgery in patients with advanced ovarian cancer. METHODS: 178 patients were divided into the research group and control group. The research group was treated with neoadjuvant chemotherapy combined with interval cytoreductive surgery, while the control group underwent primary cytoreductive surgery alone. Postoperative situation, efficacy, progression-free survival (PFS) and overall survival (OS) were compared between the two groups of patients, and the postoperative influencing factors for the patients were analyzed. RESULTS: The operation time, intraoperative blood loss and ascites volume in patients in the research group were shorter and lower than those in the control group (p<0.05). Univariate Cox regression analysis showed that the size of residual lesions after cytoreductive surgery, age, the International Federation of Gynecology and Obstetrics (FIGO) stage, the maximum primary tumor diameter and results of ascites cytological examination were the influencing factors for the OS of patients in the research group. The size of residual lesions after cytoreductive surgery, age and FIGO stage were independent factors affecting the postoperative OS of patients in the research group. CONCLUSION: Administering neoadjuvant chemotherapy combined with interval cytoreductive surgery for patients with advanced ovarian cancer can reduce the operation time, intraoperative blood loss and ascites volume. Besides, the size of residual lesions after cytoreductive surgery, age and FIGO stage are independent factors affecting the postoperative OS of patients.

MicroRNA-409-3p inhibits osteosarcoma cell migration and invasion by targeting catenin-δ1.

Osteosarcoma is the most common primary bone cancer which is associated with early metastatic potential and poor prognosis. However, the molecular mechanisms underlying osteosarcoma progression are not well characterized. Here, we investigated the role of miR-409-3p in osteosarcoma metastasis. Osteosarcoma tissue showed decreased expression of miR-409-3p compared to adjacent non-tumorous tissue. The expression level of miR-409-3p was negatively correlated with osteosarcoma metastasis. Overexpression of miR-409-3p in osteosarcoma cells (U2OS) inhibited cell migration and invasion. Bioinformatics analysis showed that catenin-δ1 (CTNND1, p120-catenin) is a direct target of miR-409-3p. Overexpression of miR-409-3p repressed the expression of catenin-δ1 in U2OS cells at both mRNA and protein levels. Meanwhile, miR-409-3p repressed the activity of luciferase reporter containing the 3'-untranslated region (3'UTR) of CTNND1 gene. Furthermore, expression of catenin-δ1 rescued the inhibitory effect of miR-409-3p on cell migration and invasion. Altogether, these results indicated that miR-409-3p targets catenin-δ1 to repress osteosarcoma metastasis.

Body Mass Index May Positively Correlate with Bone Mineral Density of Lumbar Vertebra and Femoral Neck in Postmenopausal Females.

BACKGROUND: Our study aimed to explore the relationship between body mass index (BMI) and bone mineral density (BMD) of lumbar vertebra and femoral neck in postmenopausal females. MATERIAL/METHODS: From September 2012 to September 2014, 236 healthy postmenopausal females who underwent physical examinations at the Women & Children's Health Care Hospital of Linyi were enrolled into our study. These subjects were divided into 3 groups: underweight group, normal weight group, and overweight group. In addition, there were 2 age stratifications: <60 years old and ≥60 years old. DPX-L type dual-energy X-ray bone densitometry (American Lunar Company) was used to measure the BMD of lumbar vertebra and femoral neck in the recruited subjects. Pearson test was used for correlation analysis. RESULTS: BMDs and T-scores of lumbar vertebra (L1-L4), femoral neck, proximal femur, and Ward's triangle region among the groups were ranked as follows: underweight group < normal weight group < overweight group. There were significant differences in body weight and BMI among the underweight, normal weight, and overweight groups (P<0.05). The T-scores of all examined anatomic locations showed significant differences between the underweight group and normal weight group, as well as between the underweight group and overweight group (both P<0.05). Only the T-scores of lumbar vertebra L2-L4 had significant differences between the normal weight group and overweight group (P<0.05). The BMDs of all anatomic components under study showed statistical differences in both age stratifications between the overweight group and underweight group, as well as between the overweight group and normal weight group (both P<0.05). When stratified above 60 years old, the BMDs of lumbar vertebra (L1, L2 and L4) showed statistical differences between the normal weight group and underweight group (P<0.05). Various factors could be ranked according to the absolute values of correlation coefficients as below: body weight, BMI, height, and age. Body weight, BMI, and height were positively correlated with the BMDs of all examined anatomic locations (P<0.05). However, age was negatively correlated with the various components of the body (lumbar vertebra L1, L2 and L4, femoral neck, proximal femur, Ward's triangle region: P<0.05; lumbar vertebra L3: P>0.05). CONCLUSIONS: Our study provides evidence that body weight and BMI are important factors affecting BMD. Postmenopausal females with low BMI are more likely to have osteopenia, and are likely to develop osteoporosis. BMI can be used as an important index to prevent osteoporosis.

microRNA-195 inhibits the proliferation, migration and invasion of cervical cancer cells via the inhibition of CCND2 and MYB expression.

The functions of microRNAs (miRNA/miR) in the development of cervical cancer remain largely undefined. The present study investigated the role of miR-195 in cervical cancer development. The expression of miR-195 mimics in the cervical cancer HeLa cell line significantly decreased the cell proliferation, migration and invasion capacities in vitro. Using miRNA target prediction algorithms and reporter assays, cyclin D2 (CCND2) and v-myb avian myeloblastosis viral oncogene homolog (MYB) were identified as direct targets of miR-195. Moreover, miR-195 repressed the expression of CCND2 and MYB in the HeLa cells at the mRNA and protein levels. Finally, the expression of miR-195 was downregulated in cervical cancer tissues compared with normal tissues. Together, these data suggest that miR-195 is a tumor suppressor in cervical cancer.