Prognostic significance of sex determining region Y-box 2,Ecadherin,and vimentin in esophageal squamous cell carcinoma

BACKGROUND Sex determining region Y-box 2(SOX2) can promote squamous cell carcinoma(SSC) because it regulates the migration and invasion of several different types of squamous carcinoma cells.However,few studies have examined the prognostic value of SOX2 and its effect on the epithelial-mesenchymal transition(EMT) in esophageal SSC(ESCC),a cancer characterized by high invasion and rapid metastasis.AIM To verify the relationship of SOX2 and the EMT in ESCC and determine the prognostic value and significance of SOX2 and protein markers of the EMT in ESCC.METHODS One hundred and eighty-five postsurgical ESCC patients were retrospectively examined.Immunohistochemistry was used to detect SOX2,E-cadherin,and vimentin in ESCC tissues.The chi-square test was used to determine the relationships of the expression of these proteins with clinical data.Kaplan-Meier survival curves were used to evaluate factors associated with overall survival(OS).RESULTS SOX2 and vimentin had high expression in ESCC tissues and correlated with the depth of local carcinoma invasion.SOX2 expression had positive correlations with tumor size,vimentin expression,and the EMT,and a negative correlation with Ecadherin expression.Expression of SOX2 and vimentin had negative correlations with OS.SOX2 expression was an independent prognostic risk factor for poor OS in patients with ESCC.CONCLUSION SOX2 expression was an independent risk factor for OS in patients with ESCC and its expression had a positive correlation with the expression of vimentin,a classic marker of the EMT.SOX2 promoted the migration and invasion of ESCC,and this may related to its effect on vimentin in promoting the EMT.

Sox2, a key factor in the regulation of pluripotency and neural differentiation

Sex determining region Y-box 2(Sox2), a member of the SoxB1 transcription factor family, is an important transcriptional regulator in pluripotent stem cells(PSCs). Together with octamer-binding transcription factor 4 and Nanog, they co-operatively control gene expression in PSCs and maintain their pluripotency. Furthermore, Sox2 plays an essential role in somatic cell reprogram-ming, reversing the epigenetic configuration of differ-entiated cells back to a pluripotent embryonic state. In addition to its role in regulation of pluripotency, Sox2 is also a critical factor for directing the differentiation of PSCs to neural progenitors and for maintaining the properties of neural progenitor stem cells. Here, we review recent findings concerning the involvement of Sox2 in pluripotency, somatic cell reprogramming and neural differentiation as well as the molecular mecha-nisms underlying these roles.

Sex-determining Region of Y Chromosome-related High-mobility-group Box 2 in Malignant Tumors： Current Opinions and Anticancer Therapy

Objective： To gain insight into the mechanism by which sex-determining region of Y chromosome （SRY）-related high-mobility-group box 2 （SOX2） involved in carcinogenesis and cancer stem cells （CSCs）. Data Sources： The data used in this review were mainly published in English from 2000 to present obtained from PubMed. The search terms were ＂SOX2,＂ ＂cancer,＂ ＂tumor＂ or ＂CSCs.＂ Study Selection： Articles studying the mitochondria-related pathologic mechanism and treatment of glaucoma were selected and reviewed. Results： SOX2, a transcription factor that is the key in maintaining pluripotent properties of stem cells, is a member of SRV-related high-mobility group domain proteins. SOX2 participates in many biological processes, such as modulation of cell proliferation, regulation of cell death signaling, cell apoptosis, and most importantly, tumor formation and development. Although SOX2 has been implicated in the biology of various tumors and CSCs, the findings are highly controversial, and information regarding the underlying mechanism remains limited. Moreover, the mechanism by which SOX2 involved in carcinogenesis and tumor progression is rather unclear yet. Conclusions： Here, we review the important biological functions of SOX2 in different tumors and CSCs, and the function of SOX2 signaling in the pathobiology ofneoplasia, such as Wnt/β-catenin signaling pathway, Hippo signaling pathway, Survivin signaling pathway, P13K/Akt signaling pathway, and so on. Targeting towards SOX2 may be an effective therapeutic strategy for cancer therapy.

Primary Ovarian Small Cell Carcinoma of Pulmonary Type: Analysis of 6 Cases and Review of 31 Cases in the Literatures

Objective Primary ovarian small cell carcinoma of pulmonary type(SCCOPT)is a rare ovarian tumor with a poor prognosis.The platinum-based chemotherapy is the standard treatment.However,there is little research on the clinical characteristics of SCCOPT and the potential benefits of other treatments due to its low incidence.The study aims to investigate clinicopathological characteristics and treatment of SCCOPT.Methods We summarized the clinical,imaging,laboratorical and pathological characteristics of 37 SCCOPT cases,in which 6 cases were admitted to the Gansu Provincial Hospital from the year of 2008 to 2022 and 31 cases reported in 17 English and 3 Chinese literatures.Results The median age of the studied SCCOPT cases(n=37)was 56.00(range,22-80)years.Almost 80%of them had a stageⅢorⅣtumor.All patients underwent an operation and postoperative chemotherapy.Nevertheless,all cases had a poor prognosis,with a median overall survival time of 12 months.Immunohistochemical y,the SCCOPT of all patients showed positive expressions of epithelial markers,such as CD56 and sex-determining region of Y chromosome-related high-mobility-group box 2(SOX-2),and negative expressions of estrogen receptor,progesterone receptor,vimentin,Leu-7,and somatostatin receptor 2.The tumor of above 80%cases expressed synaptophysin.Only a few cases expressed neuron-specific enolase,chromogranin A,and thyroid transcription factor-1.Conclusions SCCOPT had a poor prognosis.SOX-2 could be a biomarker to be used to diagnose SCCOPT.

M1-type microglia can induce astrocytes to deposit chondroitin sulfate proteoglycan after spinal cord injury

After spinal cord injury(SCI),astrocytes gradually migrate to and surround the lesion,depositing chondroitin sulfate proteoglycan-rich extracellular matrix and forming astrocytic scar,which limits the spread of inflammation but hinders axon regeneration.Meanwhile,microglia gradually accumulate at the lesion border to form microglial scar and can polarize to generate a pro-inflammatory M1 phenotype or an anti-inflammatory M2 phenotype.However,the effect of microglia polarization on astrocytes is unclear.Here,we found that both microglia(CX3 CR1^(+))and astrocytes(GFAP^(+))gathered at the lesion border at 14 days post-injury(dpi).The microglia accumulated along the inner border of and in direct contact with the astrocytes.M1-type microglia(i NOS^(+)CX3 CR1^(+))were primarily observed at 3 and 7 dpi,while M2-type microglia(Arg1^(+)CX3 CR1^(+))were present at larger numbers at 7 and 14 dpi.Transforming growth factor-β1(TGFβ1)was highly expressed in M1 microglia in vitro,consistent with strong expression of TGFβ1 by microglia in vivo at 3 and 7 dpi,when they primarily exhibited an M1 phenotype.Furthermore,conditioned media from M1-type microglia induced astrocytes to secrete chondroitin sulfate proteoglycan in vitro.This effect was eliminated by knocking down sex-determining region Y-box 9(SOX9)in astrocytes and could not be reversed by treatment with TGFβ1.Taken together,our results suggest that microglia undergo M1 polarization and express high levels of TGFβ1 at 3 and 7 dpi,and that M1-type microglia induce astrocytes to deposit chondroitin sulfate proteoglycan via the TGFβ1/SOX9 pathway.The study was approved by the Institutional Animal Care and Use Committee of Anhui Medical University,China(approval No.LLSC20160052)on March 1,2016.

SOX13 gene downregulation in peripheral blood mononuclear cells of patients with Klinefelter syndrome

Klinefelter syndrome(KS)is the most common sex chromosome disorder in men.It is characterized by germ cell loss and other variable clinical features,including autoimmunity.The sex-determining region of Y(SRY)-box 13(Sox13)gene is expressed in mouse spermatogonia.In addition,it has been identified as islet cell autoantigen 12(ICA12),which is involved in the pathogenesis of autoimmune diseases,including type 1 diabetes mellitus(DM)and primary biliary cirrhosis.SOX13 expression has never been investigated in patients with KS.In this age-matched,case-control study performed on ten patients with KS and ten controls,we found that SOX13 is significantly downregulated in peripheral blood mononuclear cells of patients with KS compared to controls.This finding might be consistent with the germ cell loss typical of patients with KS.However,the role of SOX13 in the pathogenesis of germ cell loss and humoral autoimmunity in patients with KS deserves to be further explored.

Emerging signals regulating liver tumor initiating cells

Tumor initiating cells(TICs)have been identified as cells that account for tumor heterogeneity.Recent studies demonstrated that genes controlling stem cell biology play key roles in maintaining TICs and promote their development into cancer.In this review,we summarize findings from human and animal studies that indicate the presence of TICs during liver cancer development.Markers identified for liver development and regeneration are used to identify liver cancer TICs.Expression of these markers is often upregulated in human hepatocellular carcinoma(HCC)specimen.Using flow cytometry analysis and lineage tracing approaches,the presence of TICs is confirmed.Expression of TIC markers and the presence of TICs are also observed in genetically modified animals that target genes that are frequently altered in human HCC.The presence of these TICs represents a major challenge for therapeutic development.Elucidating signals that can regulate the fate,transformation and growth of liver TICs is an emerging need in liver research.Sex-determining region Y-box 9(SOX9)has recently become an important marker for liver TICs.Here,we summarize the role of SOX9 in TICs and its potential interaction with other signals.This includes the Notch-Numb signal that controls asymmetrical-symmetrical cell division,Wnt-b-catenin signal that maintains cell fate and transforming growth factor(TGF)-b signal that acts as upstream inducers.