Inflammation-related markers and prognosis of alpha-fetoprotein producing gastric cancer

BACKGROUND Inflammation-related markers including neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),monocyte-to-lymphocyte ratio(MLR),systemic immune-inflammation index(SII),systemic inflammation response index(SIRI)and prognostic nutritional index(PNI)could reflect tumor immune microenvironment and predict prognosis of cancers.However,it had not been explored in alpha-fetoprotein(AFP)producing gastric cancer(GC).AIM To determine the predictive value of inflammation-related peripheral blood markers including as NLR,PLR,MLR,SII,SIRI and PNI in the prognosis of AFPproducing GC(AFPGC).Besides,this study would also compare the differences in tumor immune microenvironment,clinical characteristics and prognosis between AFPGC and AFP-GC patients to improve the understanding of this disease.METHODS 573 patients enrolled were retrospectively studied.They were divided into AFP+group(AFP≥20 ng/mL)and AFP-group(AFP<20 ng/mL),comparing the levels of NLR/PLR/MLR/SII/SIRI/PNI and prognosis.In AFP+group,the impact of NLR/PLR/MLR/SII/SIRI/PNI and their dynamic changes on prognosis were further explored.RESULTS Compared with AFP-patients,AFP+patients had higher NLR/PLR/MLR/SII/-SIRI and lower PNI levels and poorer overall survival(OS).In the AFP+group,mortality was significantly lower in the lower NLR/PLR/MLR/SII/SIRI group and higher PNI group.Moreover,the dynamic increase(NLR/PLR/MLR/SII/-SIRI)or decrease(PNI)was associated with the rise of mortality within 1 year of follow-up.CONCLUSION Compared with AFP-patients,the level of inflammation-related peripheral blood markers significantly increased in AFP+patients,which was correlated with OS of AFP+patients.Also,the gradual increase of SII and SIRI was associated with the risk of death within one year in AFP+patients.AFPGC should be considered as a separate type and distinguished from AFP-GC because of the difference in tumor immune microenvironment.It requires basic experiments and large clinical samples in the future.

Complementary monogamy and polygamy properties among multipartite systems

Monogamy and polygamy relations are essential properties of quantum entanglement,which characterize the distributions of entanglement in multipartite systems.In this paper,we establish the general monogamy relations forγ-th(0≤γ≤α,α≥1)power of quantum entanglement based on unified-(q,s)entanglement and polygamy relations forδ-th(δ≥β,0≤β≤1)power of entanglement of assistance based on unified-(q,s)entanglement of assistance,which provides a complement to the previous research in terms of different parameter regions ofγandδ.These results are then applied to specific quantum correlations,e.g.,entanglement of formation,Renyi-q entanglement of assistance and Tsallis-q entanglement of assistance to get the corresponding monogamy and polygamy inequalities.Moreover,typical examples are presented for illustration.

Effect of Optimized Concentrations of Basic Fibroblast Growth Factor and Epidermal Growth Factor on Proliferation of Fibroblasts and Expression of Collagen： Related to Pelvic Floor Tissue Regeneration

Background： Fibroblasts were the main seed cells in the studies of tissue engineering of the pelvic floor ligament. Basic fibroblast growth factor （bFGF） and epidermal growth factor （EGF） were widely studied but at various concentrations. This study aimed to optimize the concentrations of combined bFGF and EGF by evaluating their effects on proliferation and collagen secretion of fibroblasts. Methods： Fibroblasts were differentiated from rat adipose mesenchymal stem cells （ADSCs）. Flow cytometry and immunohistochemistry were used for cell identification. The growth factors were applied at concentrations of 0, 1, 10, and 100 ng/ml as three groups： （1） bFGF alone, （2） EGF alone, and （3） bFGF mixed with EGF. Cell proliferation was evaluated by Cell Counting Kit-8 assays. Expression of Type I and III collagen （Col-I and Col-1II） mRNAs was evaluated by real-time quantitative reverse transcription-polymerase chain reaction. Statistical analysis was performed with SPSS software and GraphPad Prism using one-way analysis of variance and multiple t-test. Results： ADSCs were successfully isolated from rat adipose tissue as identified by expression of typical surface markers CD29, CD44, CD90, and CD45 in flow cytometry. Fibroblasts induced from ADSC, compared with ADSCs, were with higher mRNA expression levels of Col I and Col III （F = 1.29, P = 0.0390）. bFGF, EGF, and the mixture ofbFGF with EGF can enhanced fibroblasts proliferation, and the concentration of 10 ng/ml of the mixture ofbFGF with EGF displayed most effectively （all P 〈 0.05）. The expression levels of Col-I and Col-Ill mRNAs in fibroblasts displayed significant increases in the 10 ng/ml bFGF combined with EGF group （all P 〈 0.05）. Conclusions： The optimal concentration of both bFGF and EGF to promote cell proliferation and collagen expression in fibroblasts was 10 ng/ml at which fibroblasts grew faster and secreted more Type I and III collagens into the extracellular matrix, which might contribute to the stability of the pelvic floor microenvironment.

Identification of new fusion genes and their clinical significance in endometrial cancer

Background:Fusion genes may play an important role in tumorigenesis, prognosis, and drug resistance;however, studies on fusion genes in endometrial cancer (EC) are rare. This study aimed to identify new fusion genes and to explore their clinical significance in EC. Methods: A total of 28 patients diagnosed with EC were enrolled in this study. RNA sequencing was used to obtain entire genomes and transcriptomes. STAR-comparison and STAR-fusion prediction were applied to predict the fusion genes. Chi-square tests and Student t tests were used to verify the clinical significance with SPSS 13.0 software. Results: New fusion genes were found, and the number of fusion genes varied from 3 to 110 among all patients with EC. The type of fusion genes varied and included messenger RNA (mRNA)-mRNA, long non-coding RNA (lncRNA)-lncRNA, and lncRNAmRNA. There were six fusion genes with high fusion rates, namely, RF11-123010.4-GRIP1-RP11-444D3.1-SOXS,RP11-680G10.1-GSE1,NRIP1-AF127936.7,RP11-96H19.1-RP11-446N19.1,andDPH7-PTP4A3. Further studies showed that these fusion genes are related to stage, grade, and recurrence, in which NRIP1-AF127936.7andDPH7-PTP4A3 were found only in stage Ⅲ patients with EC. DPH7-PTP4A3was found in grades 2 and 3, and recurrent patients with EC. Conclusion: Fusion genes play an essential role in EC. Six genes that are overexpressed with high fusion rates are identified. NRIP1-AF127936.7and DPH7-PTP4A3 might be related to stage, and DPH7-PTP4A3 be related to grade and recurrence.

Dual-specificity Phosphatase 1 Deficiency Induces Endometrioid Adenocarcinoma Progression via Activation of Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase Pathway

Background： Previously, we reported that dual-specificity adenocarcinoma （EEA）. However, the role of DUSP1 medroxyprogesterone （MPA） are still unclear. phosphatase I （DUSPI） was differentially expressed in endometrioid in EEA progression and the relationship between DUSPI and Methods： The expression of DUSPI in EEA specimens was detected by immunohistochemical analysis. The effect of DUSPI on cell proliferation was analyzed by Cell Counting Kit 8 and colony formation assay, and cell migration was analyzed by transwell assay. MPA-induced DUSPI expression in EEA cells was measured by Western blot. Results： DUSPI expression was deficient in advanced International Federation of Gynecology and Obstetrics stage, high-grade and myometrial invasive EEA. In EEA cell lines （HeclA, Hecl B, RL952, and Ishikawa）, the DUSP1 expression was substantially higher in lshikawa cells than in other cell lines （P 〈 0.05）. Knockdown ofDUSP I promoted lshikawa cells proliferation, migration, and activation of mitogen-activated protein kinases/extracellular signal-regulated kinase （MAPK/Erk） pathway. MPA-induced DUSP1 expression and inhibited MAPK/Erk pathway in Ishikawa cells. Conclusions： Our data suggest that DUSP1 deficiency promotes EEA progression via MAPK/Erk pathway, which may be reversed by MPA, suggesting that DUSP I may serve as a potential therapeutic target for the treatment of EEA.

Intra-tumor heterogeneity for endometrial cancer and its clinical significance

Background:Management of tumors has become more complex owing to tumor heterogeneity.Fewer studies have been performed on intra-tumor heterogeneity of endometrial cancer(EC)until now.Therefore,it is of great clinical value to explore the intra-tumor heterogeneity of EC based on clinical features and gene expression profiles.Methods:A total of 1688 patients with EC were screened and 114 patients were finally selected,including specimens from 84 patients with primary EC without relapse(PE)and the paired metastases(P-M)specimens,as well as specimens from 30 patients with primary EC with relapse(RPE)and the paired relapsed EC(P-RE)specimens.Microarray and RNA-seq were used to detect gene expression of EC samples.Clinicopathological characteristics and molecular data were compared between PE and P-M groups and between RPE and P-RE groups to explore the intra-tumor heterogeneity of EC.Results:The clinical intra-tumor spatial heterogeneity of pathological type,grade,ER status,and PR status between PE and P-M were 17.9%,13.1%,28.6%,and 28.6%,respectively.The clinical intra-tumor spatiotemporal heterogeneity of pathological type,grade,ER status,and PR status between RPE and P-RE were 16.7%,33.3%,25.0%,and 37.5%,respectively.Cluster analysis sorts EC samples based on progression type of lesion and their pathological type.There were differentially expressed genes between PE and P-M and between RPE and P-RE,of which gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis were mainly enriched in cell proliferation,the p53 signaling pathway,etc.Conclusions:Clinical and molecular data showed that there was spatiotemporal heterogeneity in intra-tumor of EC,which may add to the complexity of diagnosis and therapeutics for EC.Considering the intra-tumor heterogeneity,sequential chemotherapy and precision medicine may be a more suitable treatment plan for EC.