ObjectiveUsing data from NHANES 2007–2018, to examine the association between WWI (weight-adjusted waist index) index and prevalence of kidney stones.MethodsUsing multiple logistic regression analysis of the National Health and Nutrition Examination Survey (NHANES) 2007–2018, we evaluated the association between WWI index and the prevalence of kidney stones, followed by subgroup analysis of sensitive populations. Smooth curve fitting was used to determine whether there was a non-linear relationship between the WWI index and kidney stone prevalence, and threshold effect analysis was used to test this relationship.ResultsAmong 29,280 participants, 2,760 self-reported renal calculi. After adjustment for all confounders, there was a positive association between WWI and kidney stone prevalence (OR = 1.20, 95% CI: 1.12, 1.28), and this positive association was stronger with increasing WWI (and P = 0.01 for trend). Our results indicate a non-linear positive correlation between WWI index and kidney stones, with the saturation threshold effect analysis and the most important threshold value at 11.02. According to subgroup analysis, WWI showed the strongest association with kidney stone prevalence in participants aged 20–39 years, males, other US ethnic groups, and participants without hypertension and diabetes.ConclusionIncreased WWI is positively associated with increased incidence of kidney stones, and increased WWI is a high risk for kidney stones that should be treated with caution. This association should be more pronounced in people between the ages of 20 and 39 years, in men, in other US ethnic populations, and in participants who do not have hypertension or diabetes.

Background Triple-negative breast cancer (TNBC) has the poorest prognosis among all breast cancer subtypes. While several tumor types are excepted to have a curative response to immunotherapy through the AT-rich interaction domain 1A (ARID1A) gene, its role in TNBC remains unclear.Methods The expression of the ARID1A gene and immune infiltration in TNBC were analyzed by way and function enrichment analysis. Additionally, 27 gene mutations, including ARID1A mutation, were detected in paraffin-embedded TNBC specimens and normal breast specimens using Next Generation Sequencing (NGS). Immunohistochemical staining was employed to detect the expression of AIRD1A, TP53, Ki67, CD4, CD8, and PD-L1 proteins in TNBC and the adjacent normal tissue samples.Results The bioinformatics analysis revealed that ARID1A was mutated in TNBC and significantly associated with tumor immune infiltration. NGS analysis showed a high mutation rate of ARID1A (35%) in TNBC, but the mutation status of ARID1A was not associated with age at onset, lymph node metastasis, pathological grade, or Ki67 index. Low expression or loss of AIRD1A was more commonly observed in TNBC tissues (36/108) as compared to normal tissues (3/25). Positive expression of CD8 and PD-L1 was observed in TNBC tissues with low ARID1A expression. ARID1A mutation was associated with low protein expression, and patients with ARID1A mutation or low protein expression had shorter progression-free survival.Conclusion The ARID1A mutation and low expression are associated with poor prognosis and high immune infiltration in TNBC, and might be biomarkers for TNBC prognosis and immunotherapy efficacy.

<p>Details for variant processing, analysis of TCGA data, and the FM mutation hotspot caller.</p>

High podoplanin (PDPN) expression correlates with poor prognosis in various cancers. However, the expression and clinical value of PDPN in glioma are unclear. In this study, PDPN expression was compared in 227 glioma tissues and 22 paired non-neoplastic tissues, and its association with prognostic factors was statistically analyzed. The effect of PDPN knockdown on the proliferation ability of glioma cells (U87MG and U118MG cell lines) was assessed along with the underlying molecular mechanism. Overexpression of PDPN was observed in the majority of glioma tissues compared with the expression in normal tissues. PDPN overexpression was positively correlated with IDH wild-type status, TERT promoter mutation status, and ATRX retention status, and was negatively correlated with 1p/19q codeletion status. The expression level of PDPN was positively correlated with the glioma grade in the diffuse astrocytoma, IDH wild-type. High PDPN expression was also negatively correlated with survival in astrocytoma patients with IDH mutation or wild-type and in glioblastoma patients with IDH wild-type. Grade, radiochemotherapy, and PDPN overexpression emerged as independent indicators for a poor prognosis of glioma patients. PDPN knockdown suppressed proliferation and reduced p-Akt and p-mTOR protein expression in glioma cells. PDPN is a potential biomarker or therapeutic target for glioma that is closely associated with tumor grade and poor prognosis, which may play a role in enhancing cell proliferation via Akt/mTOR signaling.

This file contains supplemental tables S1-S7. The data contained are as follows: (Table S1) Gene lists on the FoundationOne assay, (Table S2) Sample counts per disease, (Table S3) Foundation Medicine sample counts compared to TCGA sample counts, (Table S4) Genes with altered frequencies between local and metastatic disease, (Table S5) Merged MutationAssessor and PolyPhen-2 outputs, (Table S6) Enrichment of NOTCH1 alterations across diseases, (Table S7) Curated list of tumor suppressor genes on the FoundationOne assay.

AIM:To investigate the relationship between expression of C-MYC protein and clinicopathologic characteristics in angioimmunoblastic T-cell lymphoma (AITL), then discuss the prognosis. METHODS:Patient samples were collected and made into tissue microarray for the same experimental condition. Pathomorphological features and immunohistochemistry of specific markers were used to determine the diagnosis of AITL. Epstein-Barr virus (EBV) infection was detected by EBV-encoded small RNA by in situ molecular hybridizations. B cells atypical hyperplasia was explored by the immunohistochemistry and gene rearrangement, C-MYC protein was expressed by the immunohistochemical staining and C-MYC gene abnormalities were detected by fluorescence in situ hybridization (FISH). 44 AITL patients were divided into two groups and the relation among C-MYC protein, EBV infection and B cells hyperplasia was observed. We followed up the overall survival rate (OS) and progression-free survival (PFS), and analyzed C-MYC protein, and the relationship between the prognosis of survival. RESULTS:Among 44 AITL patients, 29 cases (65.9%) were C-MYC protein-positive, and 32 (32/44, 72.3%) were EBV-positive. The expression rate of C-MYC protein in the high-risk group ranked by international prognostic index (IPI) and stage III-IV were higher than that in the low-risk group and stage I-II (P<0.05). The expression rate of C-MYC protein was higher in B cells excessive proliferation group, including simple hyperplasia, atypical hyperplasia, monoclonal B cells hyperplasia, and the diffuse large B lymphoma than in the low-proliferation group (P<0.05). The expression rate of C-MYC protein in EBV-positive patients was indifferent compared with the negative group (P>0.05). C-MYC gene rearrangement was not found in any samples, while the multi-copies of the C-MYC gene were found in only one case. As followed, 5-year OS was significantly low, and there was no significant difference in OS between the C-MYC protein-positive and negative groups. PFS in the positive group was significantly lower than that of the negative group. The difference in response to treatment between the two groups was statistically significant (P<0.05). CONCLUSION:We discussed the clinicopathologic characteristics and significance in AITLs, which predominantly express MYC-protein in <50% of cells, lacking C-MYC gene rearrangement. C-MYC protein-positive or negative expression was closely related to B cells excessive proliferation. C-MYC protein may be used as an indicator to judge the malignancy and to predict the prognosis of AITL.

Abstract Glioblastoma multiforme (GBM) is an extremely aggressive and malignant tumor of the central nervous system in adults. Therefore, understanding its pathogenesis is urgently needed. This study aimed to investigate the role of long noncoding RNA (lncRNA) highly upregulated in liver cancer (HULC) in GBM. The levels of lncRNA HULC and proteins in PI3K/AKT pathway in GBM tissues were measured. Kaplan–Meier method was used to analyze the survival. An in-vivo tumor xenograft model in mice was constructed and monitored. In GBM SGH44 and U87 cells, the proliferation, migration, invasion, cell cycle and apoptosis, cellular expression of proteins in PI3K/AKT pathway, and that of lncRNA HULC and microRNA (miR)-128 were determined. The interactions between lncRNA HULC, miR-128, and tenascin-R (TNR) were verified. The result showed lncRNA HULC was an oncogene that can promote cell proliferation, migration, and invasion in human GBM tissue, orthotopic transplantation in mice, and GBM cell lines. LncRNA HULC was further confirmed to affect TNR expression via sponging miR-128 and activating the PI3K/AKT pathway to promote cell proliferation in GBM. LncRNA HULC can affect the expression of TNR protein, activate the PI3K/AKT pathway, promote GBM cell proliferation, migration, and invasion, and inhibit apoptosis mediated by miR-128.

Histological imaging is essential for the biomedical research and clinical diagnosis of human cancer. Although optical microscopy provides a standard method, it is a persistent goal to develop new imaging methods for more precise histological examination. Here, we use nitrogen-vacancy centers in diamond as quantum sensors and demonstrate micrometer-resolution immunomagnetic microscopy (IMM) for human tumor tissues. We immunomagnetically labeled cancer biomarkers in tumor tissues with magnetic nanoparticles and imaged them in a 400-nm resolution diamond-based magnetic microscope. There is barely magnetic background in tissues, and the IMM can resist the impact of a light background. The distribution of biomarkers in the high-contrast magnetic images was reconstructed as that of the magnetic moment of magnetic nanoparticles by employing deep-learning algorithms. In the reconstructed magnetic images, the expression intensity of the biomarkers was quantified with the absolute magnetic signal. The IMM has excellent signal stability, and the magnetic signal in our samples had not changed after more than 1.5 y under ambient conditions. Furthermore, we realized multimodal imaging of tumor tissues by combining IMM with hematoxylin-eosin staining, immunohistochemistry, or immunofluorescence microscopy in the same tissue section. Overall, our study provides a different histological method for both molecular mechanism research and accurate diagnosis of human cancer.

Background: OSBPL3 is overexpressed in a variety of malignancies and is closely associated with tumor growth and metastasis. However, its expression and function in colorectal cancer (CRC) are unclear. We aimed to investigate its prognostic and therapeutic value in this disease by detecting its expression in CRC and its correlation with the clinicopathological characteristics and prognosis of patients. Methods: A total of 92 CRC samples were included in this study. According to the 2020 WHO diagnostic criteria, the criteria of the American Joint Committee on Cancer (AJCC) 8th edition staging system were used. OSBPL3 and Ki-67 expression in these samples was detected by immunohistochemistry. OSBPL3 mRNA expression was detected by qRT-PCR. KRAS/NRAS mutations were detected by an amplification refractory mutation system (ARMS). Data analysis was performed using the statistical analysis software Prism 8. Results: OSBPL3 was found to be significantly overexpressed in CRC tumor tissues and was associated with worse progression-free survival and overall survival in patients. Additionally, OSBPL3 expression was negatively correlated with the degree of tumor differentiation. KRAS mutations were detected in approximately 32.6% of patients and were significantly associated with high OSBPL3 expression. In addition, OSBPL3 and Ki-67 expression was significantly correlated. Conclusions: OSBPL3 is highly expressed in CRC samples and predicts a worse prognosis. OSBPL3 may become a new potential therapeutic target for CRC.

Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. More and more studies have shown that the tumor immune microenvironment (TME) of TNBC is closely related to its poor prognosis and early metastasis. We try to explain how tumor-associate macrophages (TAMs), an important component of the TME, function in the matrix of TNBC. Therefore, we induced THP-1 cells to become M1-TAMs and M2-TAMs, investigated their influence on breast cancer cells. 82 TNBC paraffin samples were made into tissue microarrays. The expression of macrophages makers were measured by immunohistochemistry. Scratch assay, Transwell assay, CCK-8 cell proliferation assay were performed in the co-culture system of breast cancer cells lines and macrophages to observe the invasion and proliferation ability of breast cancer cell lines. Western Blot (WB) was performed to detect the expression of E-cadherin (CDH1) and N-cadherin (CDH2). M2-TAMs were more numerous than M1-TAMs in the matrix of TNBC cancer nests and associated with poor prognosis. M2-TAMs promoted the invasion, migration, and proliferation of TNBC cells. M1-TAMs had inhibitory effects. In MCF-7 cells, WB showed a decrease in CDH1 and an increase in CDH2. In MDA-MB-231 cells and BT549 cells, CDH2 expression was reduced and CDH1 expression was increased. All of the above results were statistically significant, p < 0.001. M2-TAMs were more numerous in TNBC and associated with poor prognosis. M2-TAMs promoted the invasion, migration, and proliferation of breast cancer cells. The mechanism may be related to the epithelial-mesenchymal transition.

目的 探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)中EGFR、ALK及ROS1基因突变和PD-L1蛋白表达与临床病理特征的相关性.方法 收集84例NSCLC标本,采用突变扩增阻止系统(amplification refractory mutation sys-tem,AMRS)技术检测EGFR基因突变;采用FISH技术检测ALK和ROS1基因重排;采用二代测序(next generation se-quencing,NGS)技术检测EGFR、ALK、ROS1基因突变;采用免疫组化法检测PD-L1(22 C3)蛋白表达.结果 84例NSCLC中,45例EGFR突变,2例ALK融合,1例ROS1融合;PD-L1不表达38例(45.2％),低表达23例(27.4％),高表达23例(27.4％).EGFR突变与患者性别、年龄、是否吸烟、肿瘤病理类型及分化程度有关(P<0.05),EGFR突变和ALK或ROS1重排具有排他性,未见同时出现.PD-L1表达与肿瘤病理类型有关(P<0.05),PD-L1蛋白表达与EGFR、ALK、ROS1基因突变等无关(P>0.05).结论 NSCLC患者应同时行多基因检测和免疫相关蛋白检测,有助于筛选靶向治疗及免疫治疗对象,指导临床个体化精准治疗.

AIMS:To investigate the clinicopathological and molecular characteristics of uterine tumours resembling ovarian sex cord tumours (UTROSCTs) and the value of molecular diversity in the clinical diagnosis and treatment.METHODS:Five patients with UTROSCT were enrolled, and their clinical data, pathological morphologies, immunophenotypes and molecular features were analysed. Fluorescence in situ hybridisation for NCOA1, NCOA2, NCOA3, JAZF1 and PHF1 and next-generation sequencing for 27 homologous recombination/repair (HRR) pathway genes were performed on five and three UTROSCT specimens, respectively.RESULTS:All five patients were treated for abnormal uterine bleeding and grossly presented with intrauterine polyps. Under a microscope, tumour cells grew diffusely and presented a cordlike arrangement and glandular duct-like structures, with nuclei ranging from round to oval, vesicular chromatin and visible nucleoli in some cases. The mitotic count was less than 3/10 high-power fields. Immunohistochemistry showed sex cord, epithelial cell and smooth muscle cell biomarkers and diffuse, strong staining for B cell lymphoma-2 (BCL-2). NCOA1 and NCOA3 rearrangements were identified in 80% (4/5) of the cases. JAZF1 and PHF1 rearrangements were not detected in any of five patients. HRR pathway gene mutations were detected in all three patients, including FANCE, ATR and ARID1A mutations in one case each.CONCLUSION:UTROSCT is a rare mesenchymal tumour, and biopsy specimens are easily misdiagnosed. UTROSCT diagnosis requires the combined use of biomarkers and molecular detection. BCL-2 has potential diagnostic value as a marker. UTROSCT can have mutations related to the HRR pathway, suggesting that this tumour type may be sensitive to platinum/poly (ADP-ribose) polymerase inhibitors.

目的 探讨甲状腺细针穿刺细胞学诊断中滤泡性肿瘤的临床病理学特征及鉴别诊断.方法 回顾性分析36例细胞学诊断为可疑滤泡性肿瘤后行手术切除的病例,分析细胞学特征及组织学诊断结果.结果 细胞学诊断为可疑滤泡性肿瘤的组织学诊断结果多样,包括良性滤泡性结节15例(41.7％)、滤泡性肿瘤14例(38.9％)、乳头状癌5例(13.9％)、甲状旁腺肿瘤2例(5.6％).其中滤泡性肿瘤包括滤泡性腺瘤5例(13.9％)、嗜酸细胞腺瘤3例(8.3％)、滤泡性癌3例(8.3％)、恶性潜能未定的滤泡性肿瘤2例(5.6％)以及具有乳头状核特点的非浸润性甲状腺滤泡性肿瘤1例(2.8％).这组病变均呈现以滤泡结构为主的排列方式,但在细胞形态上却存在差异.结论 "滤泡性肿瘤/可疑滤泡性肿瘤"的术后组织病理类型涵盖范围广泛.对于滤泡结构为主的细胞学涂片,无论是否具有典型乳头状癌细胞核特点,均应结合超声、检验及分子检测结果进行综合评估,避免漏诊及过度诊断.细胞学医师客观的诊断及描述更利于滤泡性肿瘤/可疑滤泡性肿瘤准确的临床管理.

Purpose Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. LncRNA HOTAIR (HOx Transcript AntIsense RNA) and Galectin-3 are involved in PTC. This study explored the clinical effect of lncRNA HOTAIR/Galectin-3 on PTC patients. Methods Subjects were assigned into PTC (160 cases) and benign thyroid tumor groups (150 cases). Fasting peripheral venous blood was collected. LncRNA HOTAIR/Galectin-3 expressions in serum were detected. Subjects were assigned into HOTAIR/Glactin-3 high/low expression groups and their correlation with age, gender, BMI, tumor size, pathological stage, TSH, TPO-Ab, and TG-Ab in PTC was analyzed. Receiver operating characteristic (ROC) curve was conducted on diagnostic efficacy of HOTAIR or/and Galectin-3. The difference of area under the curve (AUC) was compared and analyzed. Results HOTAIR and Glactin-3 were higher in PTC group and correlated with tumor pathological stage. Higher HOTAIR/Glactin-3 expression indicated a more advanced TNM stage. LncRNA HOTAIR was positively correlated with TPO-Ab and TG-Ab. AUC of HOTAIR for PTC diagnosis was 0.895, with 96.00% specificity and 80.63% sensitivity. AUC of Glactin-3 for PTC diagnosis was 0.817, with 66.67% specificity and 78.75% sensitivity. AUC of HOTAIR combining with Glactin-3 for PTC diagnosis was 0.969 with 96.00% specificity and 87.50% sensitivity. AUC of lncRNA HOTAIR was higher than that of Glactin-3, while AUC of the combination was higher than that of lncRNA HOTAIR or Glactin-3. Conclusion LncRNA HOTAIR and Glactin-3 were highly expressed in PTC. The combination detection of lncRNA HOTAIR/Glactin-3 had higher diagnostic efficiency on the differential diagnosis of benign thyroid tumor and PTC.

Vasculogenic mimicry (VM) has been identified as an important vasculogenic mechanism in malignant tumors, but little is known about its clinical meanings and mechanisms in oligodendroglioma. In this study, VM-positive cases were detected in 28 (20.6%) out of 136 oligodendroglioma samples, significantly associated with higher WHO grade, lower Karnofsky performance status (KPS) scores, and recurrent tumor (p < 0.001, p = 0.040, and p = 0.020 respectively). Patients with VM-positive oligodendroglioma had a shorter progress-free survival (PFS) compared with those with VM-negative tumor (p < 0.001), whereas no significant difference was detected in overall survival (OS) between these patients. High levels of phosphorylate serine/threonine kinases Ataxia-telangiectasia mutated (pATM) and phosphorylate Ataxia-telangiectasia and Rad3-Related (pATR) were detected in 31 (22.8%) and 34 (25.0%), respectively out of 136 oligodendroglioma samples. Higher expressions of pATM and pATR were both associated with a shorter PFS (p < 0.001 and p < 0.001). VM-positive oligodendroglioma specimens tended to exhibit higher pATM and pATR staining than VM-negative specimens (rs = 0.435, p < 0.001 and rs = 0.317, p < 0.001). Besides, Hypoxia-inducible factor-1α (HIF1α) expression was detected in 14(10.3%) samples, correlated with higher WHO grade and non-frontal lobe (p = 0.010 and p = 0.029). However, no obvious connection was detected between HIF1α expression and VM formation (p = 0.537). Finally, either univariate or multivariate analysis suggested that VM was an independent unfavorable predictor for oligodendroglioma patients (p < 0.001, HR = 7.928, 95%CI: 3.382-18.584, and p = 0.007, HR = 4.534, 95%CI: 1.504-13.675, respectively). VM is a potential prognosticator for tumor progression in oligodendroglioma patients. Phosphorylation of ATM and ATR linked to treatment-resistance may be associated with VM formation. The role of VM in tumor progression and the implication of pATM/pATR in VM formation may provide potential therapeutic targets for oligodendroglioma treatment.

Glioblastoma multiforme (GBM) is a life-threatening brain tumor. This study aimed to identify potential targets of the long noncoding RNA (lncRNA) HULC that promoted the progression of GBM. Two U87 cell lines were constructed: HULC-siRNA and negative control (NC). Quantitative real-time PCR (qRT-PCR) was performed to validate the transfection efficiency of HULC silencing vector. Mass spectrometry (MS) was used to generate proteomic profiles for the two cell lines. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to distinguish HULC-related genes and pathway mapping. Colony formation, Transwell, and wound-healing assays were used to investigate the functional effects of HULC knockdown on GBM. We identified 112 up-regulated proteins and 24 down-regulated proteins from a total of 4360 quantified proteins. GO enrichment illustrated that these proteins were mainly involved in organelle structure, catalysis, cell movement, and material metabolism. KEGG pathway analysis indicated that some of these proteins were significantly enriched in tight junction, metabolic pathways, and arachidonic acid metabolism. In vitro experiments demonstrated that HULC knockdown inhibited GBM cell proliferation, invasion, and migration. Our KEGG analyses revealed that PLA2G4A was a shared protein in several enriched pathways. HULC silencing significantly down-regulated the expression of PLA2G4A. Knockdown of HULC changed the proteomic characteristics of GBM and altered the behaviors of GBM cells. Specifically, we identified PLA2G4A as an HULC target in GBM. This study provides a new perspective on the mechanisms and potential drug targets of GBM treatment.

目的 探讨原发性涎腺黏液表皮样癌(mucoepidermoid carcinoma,MEC)中MAML2基因重排与临床病理特征的相关性.方法 采用荧光原位杂交(fluorescence in situ hybridization,FISH)检测28例原发性涎腺MEC中MAML2基因重排;应用免疫组化EnVision两步法检测CK7、p63、CK5/6、S-100、CD117的表达,并进行诊断及鉴别诊断.结果28例MEC中有17例(14例低级别、3例中级别)MAML2基因重排,检出率为60.7％(17/28),其中包含Warthin瘤样变异型和透明细胞变异型.MAML2基因重排与肿瘤部位、病理分级密切相关,发生在腮腺、低级别的MEC中MAML2基因重排发生率显著增高(P＜0.05),MAML2基因重排与患者年龄、性别、肿瘤最大径、淋巴结有无转移、临床分期无相关性(P＞0.05).结论MAML2基因重排与肿瘤发生部位、病理分级密切相关,MAML2基因重排阳性可以辅助诊断变异型MEC.

Gliomas are the most common and lethal malignant tumor in the central nervous system. The tumor oncogene sphingosine kinase 2 (SphK2) was previously found to be upregulated in glioma tissues and enhance glioma cell epithelial-to-mesenchymal transition through the AKT/β-catenin pathway. Nevertheless, ubiquitination of SphK2 protein has yet to be well elucidated. In this study, mass spectrometry analysis was performed to identify proteins that interacted with SphK2 protein. Co-immunoprecipitation (co-IP) and immunoblotting (IB) were used to prove the specific interaction between SphK2 protein and the neural precursor cell-expressed developmentally downregulated 4-like (NEDD4L) protein. Fluorescence microscopy was used for detecting the distribution of related proteins. Ubiquitylation assay was utilized to characterize that SphK2 was ubiquitylated by NEDD4L. Cell viability assay, flow cytometry assay, and transwell invasion assay were performed to illustrate the roles of NEDD4L-mediated SphK2 ubiquitination in glioma viability, apoptosis, and invasion, respectively. We found that NEDD4L directly interacted with SphK2 and ubiquinated it for degradation. Ubiquitination of SphK2 mediated by NEDD4L overexpression suppressed glioma cell viability and invasion but promoted glioma apoptosis. Knockdown of NEDD4L presented opposite results. Moreover, further results suggested that ubiquitination of SphK2 regulated glioma malignancy via the AKT/β-catenin pathway. in vivo assay also supported the above findings. This study reveals that NEDD4L mediates SphK2 ubiquitination to regulate glioma malignancy and may provide some meaningful suggestions for glioma treatment.

Background Long non-coding RNA (lncRNA) HULC (highly upregulated in liver cancer) is considered as an oncogenic factor for various malignant tumors. This study aimed to reveal the role of lncRNA HULC in the malignant behavior of glioblastoma (GBM) by exploring its effects on the epithelial-mesenchymal transition (EMT) and vasculogenic mimicry (VM) of human GBM. Materials and Methods The contents of VM in 27 GBM samples were assessed by immunohistochemistry-histology and their association with progress-free survival (PFS) was analyzed. Human GBM SHG44 and U87 cells were manipulated to establish stable lncRNA HULC overexpressing and silencing cells by lentivirus-based technology. The effects of altered lncRNA HULC on vasculogenic tubular formation, invasion, and EMT process in GBM cells were tested in vitro and the growth of implanted GBM tumors and their EMT process were examined in vivo. Results The numbers of VM were positively associated with disease progression, but negatively with PFS periods of GBM patients. Compared with the control vec cells, lncRNA HULC overexpression significantly increased the tubular formation, invasion, and EMT process of both SHG44 and U87 cells, accompanied by promoting the growth of implanted GBM tumors and EMT process in mice. LncRNA HULC silencing had opposite effects on the tubular formation, invasion, and EMT process as well as tumor growth of GBM cells. Conclusion LncRNA HULC stimulates the EMT process and VM in human GBM, and may be a therapeutic target for intervention of GBM.

Side Population (SP) cells are the small pool of CSC like progenitor cells, which are drug resistant and recapitulate tumor generation. The occurrence of SP cells is the major inference for attaining a better treatment and improved patient survival. In this work, we have isolated 6% SP cells from a high grade ovarian carcinoma. Our functional characterization of SP cells revealed that elevated ABCG2 and anti-apoptotic factors contribute to chemoresistance and increased life span of SP cells. Further, the overexpression of surface antigens, such as CD133 and CD117 in SP cells, are the key driving forces for high clonogenic and invasion properties of SP cells. More importantly, we found by RT-PCR aberrant activation and upregulation of Wnt/ β-catenin and its downstream targeting genes, such as DKK1 and AXIN2 in SP cells. These findings suggest that development of new anticancer drugs which target Wnt/β-catenin signaling might effectively exterminate the SP cells and aid in disease free survival.