Circular RNA circESYT2 serves as a microRNA-665 sponge to promote the progression of hepatocellular carcinoma through ENO2.

Circular RNAs (circRNAs) have emerged as crucial regulators in tumor progression, yet their specific role in hepatocellular carcinoma (HCC) remains largely uncharacterized. In this study, we utilized high-transcriptome sequencing to identify the upregulation of circESYT2 (hsa_circ_002142) in HCC tissues. Functional experiments carried out in vivo and in vitro revealed that circESYT2 played a significant role in maintaining the growth and metastatic behaviors of HCC. Through integrative analysis, we identified enolase 2 (ENO2) as a potential target regulated by circESYT2 through the competitive endogenous RNA sponge mechanism. Additional gain- or loss-of-function experiments indicated that overexpression of circESYT2 led to a tumor-promoting effect, which could be reversed by transfection of microRNA-665 (miR-665) mimic or ENO2 knockdown in HCC cells. Furthermore, the direct interaction between miR-665 and circESYT2 and between miR-665 and ENO2 was confirmed using RNA immunoprecipitation, FISH, RNA pull-down, and dual-luciferase reporter assays, highlighting the involvement of the circESYT2/miR-665/ENO2 axis in promoting HCC progression. These findings shed light on the molecular characteristics of circESYT2 in HCC tissues and suggest its potential as a biomarker or therapeutic target for HCC treatment.

ALDH2 as an immunological and prognostic biomarker: Insights from pan-cancer analysis.

Aldehyde dehydrogenase 2 (ALDH2) plays a critical role in safeguarding cells against acetaldehyde toxicity and is closely linked to human metabolism. Nevertheless, the involvement of ALDH2 in cancer remains enigmatic. This investigation seeks to comprehensively assess ALDH2's significance in pan-cancer. We conducted an all-encompassing analysis of pan-cancer utilizing multiple databases, including TCGA, linkedomicshs, UALCAN, and Kaplan-Meier plotter. We employed diverse algorithms such as EPIC, MCPCOUNTER, TIDTIMER, xCell, MCP-counter, CIBERSORT, quanTIseq, and EPIC to examine the connection between ALDH2 expression and immune cell infiltration. Single-cell sequencing analysis furnished insights into ALDH2's functional status in pan-cancer. Immunohistochemical staining was performed to validate ALDH2 expression in cancer tissues. In a comprehensive assessment, we observed that tumor tissues demonstrated diminished ALDH2 expression levels compared to normal tissues across 16 different cancer types. ALDH2 expression exhibited a significant positive correlation with the infiltration of immune cells, including CD4 + T cells, CD8 + T cells, neutrophils, B cells, and macrophages, in various tumor types. Moreover, this study explored the association between ALDH2 and patient survival, examined the methylation patterns of ALDH2 in normal and primary tumor tissues, and delved into genetic variations and mutations of ALDH2 in tumors. The findings suggest that ALDH2 could serve as a valuable prognostic biomarker in pan-cancer, closely linked to the tumor's immune microenvironment.

Alpha5 nicotine acetylcholine receptor subunit promotes intrahepatic cholangiocarcinoma metastasis.

Neurotransmitter-initiated signaling pathway were reported to play an important role in regulating the malignant phenotype of tumor cells. Cancer cells could exhibit a "neural addiction" property and build up local nerve networks to achieve an enhanced neurotransmitter-initiated signaling through nerve growth factor-mediated axonogenesis. Targeting the dysregulated nervous systems might represent a novel strategy for cancer treatment. However, whether intrahepatic cholangiocarcinoma (ICC) could build its own nerve networks and the role of neurotransmitters in the progression ICC remains largely unknown. Immunofluorescence staining and Enzyme-linked immunosorbent assay suggested that ICC cells and the infiltrated nerves could generate a tumor microenvironment rich in acetylcholine that promotes ICC metastasis by inducing epithelial-mesenchymal transition (EMT). Acetylcholine promoted ICC metastasis through interacting with its receptor, alpha 5 nicotine acetylcholine receptor subunits (CHRNA5). Furthermore, acetylcholine/CHRNA5 axis activated GSK3ß/ß-catenin signaling pathway partially through the influx of Ca2+-mediated activation of Ca/calmodulin-dependent protein kinases (CAMKII). In addition, acetylcholine signaling activation also expanded nerve infiltration through increasing the expression of Brain-Derived Neurotrophic Factor (BDNF), which formed a feedforward acetylcholine-BDNF axis to promote ICC progression. KN93, a small-molecule inhibitor of CAMKII, significantly inhibited the migration and enhanced the sensitivity to gemcitabine of ICC cells. Above all, Acetylcholine/CHRNA5 axis increased the expression of ß-catenin to promote the metastasis and resistance to gemcitabine of ICC via CAMKII/GSK3ß signaling, and the CAMKII inhibitor KN93 may be an effective therapeutic strategy for combating ICC metastasis.

Prognostic significance of RKIP, TGM2, and CMTM4 expression in oral squamous cell carcinoma.

BACKGROUND: The expression of RKIP, TGM2, and CMTM4 in oral squamous cell carcinoma (OSCC) and normal oral tissues was detected and their correlations were analyzed. The relationships between RKIP, TGM2, and CMTM4 and the clinicopathological parameters and prognosis of patients were analyzed. METHODS: Seventy cancerous and adjacent normal tissue samples were selected, recorded in the pathology department, and embedded in paraffin. Protein expression was detected by immunohistochemistry. Statistical software (SPSS 25.0, IBM Corporation) was used for the statistical analysis. The chi-squared (χ2) test was used to analyze the expression of RKIP, TGM2, and CMTM4 proteins and their clinicopathological features. Differences in RKIP, TGM2, and CMTM4 protein levels between OSCC and normal tissues were compared using a χ2 test. Survival analysis was performed using the Kaplan-Meier method, and differences between survival curves were determined using the log-rank test. The effects of RKIP, TGM2, and CMTM4 expression on patient prognosis were analyzed using a multivariate Cox proportional hazards regression model. P < .05 was considered statistically significant. RESULTS: The expression level of RKIP correlated with age and clinical stage (P < .05). TGM2 was associated with clinical stage and lymph node metastasis (P < .05). The expression of CMTM4 increased with a decrease in cancer differentiation. Kaplan-Meier survival analysis suggested that the positive expression of TGM2 and CMTM4 may predict poor prognosis in patients with OSCC. The multivariate Cox proportional hazards regression model suggested that TGM2 could be an independent prognostic factor for patients with OSCC. CONCLUSION: Combined expression of TGM2 and CMTM4 can be used as an indicator to evaluate the risk of metastasis and prognosis of OSCC.

An Angiogenic Gene Signature for Prediction of the Prognosis and Therapeutic Responses of Hepatocellular Carcinoma.

Among cancer-related deaths worldwide, hepatocellular carcinoma (HCC) ranks second. The hypervascular feature of most HCC underlines the importance of angiogenesis in therapy. This study aimed to identify the key genes which could characterize the angiogenic molecular features of HCC and further explore therapeutic targets to improve patients' prognosis. Public RNAseq and clinical data are from TCGA, ICGC, and GEO. Angiogenesis-associated genes were downloaded from the GeneCards database. Then, we used multi-regression analysis to generate a risk score model. This model was trained on the TCGA cohort (n = 343) and validated on the GEO cohort (n = 242). The predicting therapy in the model was further evaluated by the DEPMAP database. We developed a fourteen-angiogenesis-related gene signature that was distinctly associated with overall survival (OS). Through the nomograms, our signature was proven to possess a better predictive role in HCC prognosis. The patients in higher-risk groups displayed a higher tumor mutation burden (TMB). Interestingly, our model could group subsets of patients with different sensitivities to immune checkpoint inhibitors (ICIs) and Sorafenib. We also predicted that Crizotinib, an anti-angiogenic drug, might be more sensitive to these patients with high-risk scores by the DEPMAP. The inhibitory effect of Crizotinib in human vascular cells was obvious in vitro and in vivo. This work established a novel HCC classification based on the gene expression values of angiogenesis genes. Moreover, we predicted that Crizotinib might be more effective in the high-risk patients in our model.

The Biomarker Like the Correlation between Vasculogenic Mimicry, Vascular Endothelial Cadherin, Sex-DeterminingRegion on Y-Box Transcription Factor 17, and Cyclin D1 in Oesophageal Squamous Cell Carcinoma.

Background: This study aimed to explore the relationships between the sex-determining region on Y (SRY) box transcription factor 17 (SOX17), Cyclin D1, vascular endothelial cadherin (VE-cadherin), and vasculogenic mimicry (VM) in the occurrence and development of esophageal squamous cell carcinoma (ESCC). Methods: The expressions of SOX17, Cyclin D1, and VE-cadherin, as well as VM, in tissues, were determined using immunohistochemistry. SOX17, Cyclin D1, and VE-cadherin mRNA in ESCC and their corresponding adjacent normal tissues were quantified using quantitative reverse transcription polymerase chain reaction analysis. Cell invasion, migration, and proliferation were determined after the silencing of VE-cadherin. SOX17, Cyclin D1, and VE-cadherin protein were quantified using Western blotting. Results: The expression levels of SOX17, Cyclin D1, and VE-cadherin significantly correlated with the clinical characteristics of ESCC. After the VE-cadherin silencing, cell invasion, migration, and proliferation decreased, along with the Cyclin D1 levels, while the SOX17 levels increased. Conclusion: SOX17, Cyclin D1, and VE-cadherin are involved in the development of ESCC.

CHRNA5 Contributes to Hepatocellular Carcinoma Progression by Regulating YAP Activity.

Hepatocellular carcinoma (HCC) is a major health concern worldwide. A better understanding of the mechanisms underlying the malignant phenotype is necessary for developing novel therapeutic strategies for HCC. Signaling pathways initiated by neurotransmitter receptors, such as α5-nicotinic acetylcholine receptor (CHRNA5), have been reported to be implicated in tumor progression. However, the functional mechanism of CHRNA5 in HCC remains unclear. In this study, we explored the role of CHRNA5 in HCC and found that CHRNA5 expression was increased in human HCC tissues and positively correlated with the T stage (p < 0.05) and AJCC phase (p < 0.05). The KM plotter database showed that the high expression level of CHRNA5 was strongly associated with worse survival in HCC patients. Both in vitro and in vivo assays showed that CHRNA5 regulates the proliferation ability of HCC by regulating YAP activity. In addition, CHRNA5 promotes the stemness of HCC by regulating stemness-associated genes, such as Nanog, Sox2 and OCT4. Cell migration and invasion assays demonstrated that CHRNA5 significantly enhanced the metastasis of HCC by regulating epithelial-mesenchymal transition (EMT)-associated genes. Furthermore, we found that CHRNA5 regulates the sensitivity of sorafenib in HCC. Our findings suggest that CHRNA5 plays a key role in the progression and drug resistance of HCC, and targeting CHRNA5 may be a strategy for the treatment of HCC.

Expression of KAI1 and AGR2 in lung adenocarcinoma and their clinicopathological significance.

OBJECTIVE: Anticancer 1 (KAI1, tumor metastasis suppressor gene) and Anterior gradient-2 (AGR2, considered a valuable prognostic factor for some cancers) are associated with metastasis and prognosis of various types of human cancers. Nevertheless, the relationship between KAI1 and AGR2 in lung adenocarcinoma (LUAD) remains unclear. In this research, we analyzed the correlations between KAI1 and AGR2 in LUAD, and explored their correlations with clinicopathological parameters and overall survival time (OS) in patients with LUAD. METHODS: Immunohistochemical staining was used to detect KAI1 and AGR2 expression in 132 cases of LUAD samples. At the same time, all clinicopathological parameters and postoperative survival information were collected. RESULTS: AGR2 positive rate was significantly increased and KAI1 positive rate was significantly decreased in LUAD and control tissues. KAI1 positive rates were negatively correlated with tumor stage, LNM stage and TNM stage, and KAI1 subgroup positive expression of OS was significantly higher than negative KAI1 subgroup. The positive rate of AGR2 was positively correlated with tumor grade, LNM stage and TNM stage, and negatively correlated with patients OS. Active expression of AGR2 and KAI1, tumor stage, and LNM stage in multivariate analyses may be independent prognostic factors for OS in LUAD patients. CONCLUSION: KAI1 and AGR2 may be potential biomarkers for prognosis and metastasis, and they are also promising therapeutic targets for LUAD patients.

Expression of mammalian sterile 20-like kinase 1 and 2 and Yes-associated protein 1 proteins in triple-negative breast cancer and the clinicopathological significance.

BACKGROUND AND AIM: Mammalian sterile 20-like kinase 1 and 2 (MST1/2) and Yes-associated protein 1 (YAP1) are the core molecules of the Hippo signaling pathway, which have been found to be unbalanced in the occurrence of tumors and promote the development of the lesions. The present study aimed to investigate the expression of MST1/2 and YAP1 proteins in triple-negative breast cancer (TNBC) and their clinicopathological significance. METHODS: Immunohistochemistry was used to detect the expression level of protein in tissues. According to the percentage of positive cells and staining intensity, the expression intensity of MST1/2 and YAP1 proteins in the tissue samples was scored, and the correlation between MST1/2 and the clinicopathological features of TNBC were discussed. RESULTS: The expression of MST1/2 and YAP1 was associated with histological grade, metastasis, lymph node metastasis stage, and tumor node metastasis stage. The overexpression of YAP1 predicted a poor prognosis in terms of overall survival and disease-free survival time. The MST1/2 expression was associated with improved overall survival and disease free survival of the patients. CONCLUSION: MST1/2 and YAP1 may be used as prognostic indicators to evaluate the recurrence of TNBC and might become one of the new targets for breast cancer treatment.

Low PRRX1 expression and high ZEB1 expression are significantly correlated with epithelial-mesenchymal transition and tumor angiogenesis in non-small cell lung cancer.

BACKGROUND: Paired related homeobox 1 (PRRX1) and zinc finger E-box binding homeobox 1 (ZEB1) have been observed to play a vital role in the epithelial-mesenchymal transition (EMT) process in different types of cancer. The microvessel density (MVD) is the most common indicator used to quantify angiogenesis. This study aimed to investigate expression of PRRX1 and ZEB1 in non-small cell lung cancer (NSCLC) and to explore associations between these factors and tumor prognosis, EMT markers and angiogenesis. METHODS: Data for a total of 111 surgically resected NSCLC cases from January 2013 to December 2014 were collected. We used an immunohistochemical method to detect expression levels of PRRX1, ZEB1, and E-cadherin, and to assess MVD (marked by CD34 staining). SPSS 26.0 was employed to evaluate the connection between these factors and clinical and histopathological features, overall survival (OS) and tumor angiogenesis. RESULTS: PRRX1 expression was obviously lower in tumor samples than in control samples. Low expression of PRRX1, which was more common in the high-MVD group than in the low-MVD group (P = .009), correlated positively with E-cadherin expression (P < .001). Additionally, we showed that ZEB1 was expressed at higher levels in tumor samples than in normal samples. High expression of ZEB1 was associated negatively with E-cadherin expression (P < .001) and positively associated with high MVD (P = .001). Based on Kaplan-Meier and multivariate survival analyses, we found that PRRX1, ZEB1, E-cadherin and the MVD had predictive value for OS in NSCLC patients. CONCLUSIONS: These findings suggest that PRRX1 and ZEB1 may serve as novel prognostic biomarkers and potential therapeutic targets.

Metastatic brain tumors respond favorably to pyrotinib in a HER2-positive breast cancer following failure using trastuzumab.

Treatment of breast cancer (BC) with overexpression of human epidermal growth factor receptor 2 (HER2) has undergone a prosperous development with the advent of emerging small molecule tyrosine kinase inhibitors (TKIs). However, their efficacy in brain metastases (BMs) requires further investigation in both clinical trials and practice by specifically targeting this population. We herein reported a HER2-positive metastatic bilateral BC case with symptomatic diffusion of parenchymal BM after first-line treatment with trastuzumab-based regimen. She then received pyrotinib (with a disease-free survival of 5.7 months) followed by whole brain radiotherapy. Unexpectedly, under satisfactory control of intracranial parenchymal lesions, the patient based on clinical manifestations, auxiliary examinations and exclusive diagnosis was diagnosed with meningeal progression, and soon died of tumor progression. Thus, pyrotinib response differed from meningeal to parenchymal BM in BC patients, and the need of comprehensive and systematic evaluation of TKIs in some particular clinical scenarios has become a critical issue.

FOXM 1 induces Vasculogenic mimicry in esophageal cancer through ß-catenin /Tcf4 signaling.

OBJECTIVE: To investigate the role of FOXM1, ß-catenin and TCF4 in esophageal cancer (EC) and their relationship to VM (Vasculogenic Mimicry). METHODS: CCK-8 were performed to examine EC cell proliferation in FOXM1 silenced cells. EC cell migration and invasion were investigated through wound healing and Transwell assays, respectively. The formation of pipe like structures were assessed in 3D cultures. The expression of Foxm1, ß-catenin, Tcf4 and E-cadherin were investigated through western blot, RT-qPCR and immunohistochemistry (IHC) staining. The relationship between FOXM1 expression, clinic-pathological features, and overall survival (OS) were further analyzed. RESULTS: A loss of FOXM1 expression correlated with the OS of ESCC patients. FOXM1 silencing led to a loss of cell growth and suppressed cell migration and invasion in ESCC cells. VM structures were identified in ESCC tissues and human EC cell lines. Mechanistically, FOXM1 was found to promote tumorigenesis through the regulation of ß-catenin, Tcf4, and E-cadherin in EC cells, leading to the formation of VM structures. CONCLUSIONS: These findings highlight FoxM1 as a novel therapeutic target in ESCC.

Expression of CRYAB with the angiogenesis and poor prognosis for human gastric cancer.

Alpha-B crystallin (CRYAB), as a small heat shock protein, has been found to be highly expressed in various human cancers and significantly associated with the unfavorable prognosis of these tumor. Nevertheless, the clinical significance of CRYAB in gastric cancer (GC) angiogenesis remains to be elucidated. In this study, we evaluated the expression of CRYAB and CD34 in GC tissues and corresponding normal gastric specimens to explore whether high level CRYAB is related with the angiogenesis and the poor prognosis in GC.In this study, the expression of CRYAB and CD34 were detected in GC tissues and corresponding normal gastric tissues by immunohistochemical (IHC) technique. Furthermore, the relationship of CRYAB with CD34-evaluated microvessel density (MVD) and poor prognosis was also investigated.CRYAB expression level was significantly higher in GC tissue than in normal gastric mucosa tissue, and clearly mean higher MVD was observed in tumor tissues compared with non-cancerous tissues. Besides, higher MVD value was observed in positive CRYAB expression group than in negative CRYAB expression group. Statistical analysis showed that CRYAB and MVD are associated with clinicopathological features including lymph node metastasis (LNM), tumor differentiation, invasion depth, and TNM stages. Kaplan-Meier method and multivariate survival analysis indicated that high expression of CRYAB, MVD, invasion depth, TNM stages, and tumor differentiation, as well as LNM significantly correlate with poor prognosis of GC patients.High expression of CRYAB may contribute to angiogenesis, invasion and metastasis of GC. These results indicated that CRYAB was expected to be a promising molecular marker for poor prognosis and potential therapeutic target in patients with GC.

Aberrant expression of vasculogenic mimicry, PRRX1, and CIP2A in clear cell renal cell carcinoma and its clinicopathological significance.

Vasculogenic mimicry (VM) involves a tubular structure with a basement membrane that is similar to and communicates with vessels but functions independent of blood vessels to nourish tumor cells, promote tumor progression, invasion, and metastasis, with reduced 5-year survival rates. Tumor cell proliferation, invasion, and metastasis are promoted by the epithelial-mesenchymal transition (EMT). Paired-related homeobox 1 (PRRX1), a newly discovered EMT inducer, has been shown to correlate with metastasis and prognosis in diverse cancer types. Cancerous inhibitor of protein phosphatase 2A (CIP2A) was initially recognized as an oncoprotein. In this study, we aimed to investigate the expression and clinical significance of the EMT markers PRRX1, CIP2A and VM in clear cell renal cell carcinoma (CCRCC) and their respective associations with clinicopathological parameters and survival.Expression of PRRX1, CIP2A and VM in whole CCRCC tissues from 110 patients was analyzed by immunohistochemical and histochemical staining. Fisher's exact test or the chi square test was used to assess associations with positive or negative staining of these markers and clinicopathological characteristics.Positive expression of CIP2A and VM presence was significantly higher and that of PRRX1 was significantly lower in CCRCC tissues than in corresponding normal tissues. Furthermore, positive expression of CIP2A and VM was significantly associated with tumor grade, size, lymph node metastasis (LNM) stage, and tumor node metastasis (TNM) stage and inversely associated with overall survival time (OST). Moreover, levels of PRRX1 were negatively associated with tumor grade, size, LNM stage, and TNM stage. The PRRX1 subgroup had a significantly longer OST time than did the PRRX1 subgroup. In multivariate analysis, high VM and CIP2A, tumor grade, LNM stage, TNM stage, and low PRRX1 levels were identified as potential independent prognostic factors for OST in CCRCC patients.VM and expression of CIP2A and PRRX1 represent promising biomarkers for metastasis and prognosis and potential therapeutic targets in CCRCC.

Aberrant expression of MYH9 and E-cadherin in esophageal squamous cell carcinoma and their relationship to vasculogenic mimicry.

PURPOSE: To investigate whether vasculogenic mimicry (VM) exists in esophageal squamous cell carcinoma (ESCC) and to elucidate the relationship among expression of MYH9, E-cadherin and VM. METHODS: The expression of MYH9 (non-muscle myosin heavy chain 9), E-cadherin protein and VM in 120 specimens of esophageal squamous cell carcinoma (ESCC) and 120 specimens of normal esophageal mucosa were detected by using immunohistochemical and histochemical staining. RESULTS: VM channels were identified in 58 (48.33%) of the 120 ESCC specimens and none of the normal esophageal mucosa was found to have VM. The rates of expression of MYH9 and E-cad in ESCC were 57.50% and 40.00%, while rates in the control group were 13.33% and 73.33%, respectively (P<0.05). VM and the expression levels of MYH9 and E-cad were significantly connected with lymph node metastasis, serosa invasion, pTNM staging and 5-year-survival rates of patients with ESCC (P<0.05). VM was positively correlated with MYH9, but negatively correlated with E-cad, and MYH9 was negatively significantly correlated with E-cad. The 5-year-survival rates of patients with ESCC were 6.89% (4/58) in the VM group and 67.74% (42/62) in the non-VM group, 8.00% (4/50) in high MYH9 expression group and 60.00% (42/70) in low MYH9 expression group. However, the 5-year-survival rate in high E-cad expression group was 86.95% (40/46) and that in low E-cad expression group was 8.11% (6/74) (P<0.05). Cox multifactorial regression analysis demonstrated that lymph node metastasis, pTNM stage, VM and expression levels of MYH9 and E-cad were independent risk factors in patients with ESCC (P<0.05). CONCLUSION: ESCC'patients with VM had a poor differentiation and a bad clinical prognosis; Combined detection of VM, MYH9 and E-cad may play an essential role in predicting the invasion, metastasis, and progression of patients with ESCC.

Evaluation of the correlation of vasculogenic mimicry, Notch4, DLL4, and KAI1/CD82 in the prediction of metastasis and prognosis in non-small cell lung cancer.

Vasculogenic mimicry (VM) is a new blood supply style in tumors and has long been treated as a useful factor in malignant tumor metastasis and prognosis. Notch4 (a marker of Notch signaling pathway receptors), DLL4 (a marker of Notch signaling pathway ligands) and KAI1/CD82 (a suppressor gene of tumor metastasis) are all effective predictive factors for tumor metastasis. In this study, we analyzed correlations among VM, Notch4, DLL4, and KAI1/CD82 in non-small cell lung cancer (NSCLC), and their respective associations with patients' clinicopathological parameters and survival rate in NSCLC.Positive rates of VM, Notch4, DLL4, and KAI1/CD82 in 189 whole NSCLC specimens were detected by histochemical and immunohistochemical staining. Moreover, patients' clinicopathological information was also collected.Positive rates of VM, Notch4, and DLL4 were significantly higher, and levels of KAI1/CD82 were significantly lower in NSCLC than in normal lung tissues. Positive rates of VM, Notch4, and DLL4 were positively associated with tumor size, lymph node metastasis (LNM), distant metastasis (DM) and tumor-node-metastasis (TNM) stage, and inversely with patients, overall survival (OS) time and positive rate of DLL4 were positively associated with tumor grade. Levels of KAI1/CD82 were negatively associated with tumor size, LNM, DM, and TNM stage. The KAI1/CD82+ subgroup had significantly longer OS time than did the KAI1/CD82- subgroup. In multivariate analysis, high VM, Notch4, DLL4 levels, tumor size, LNM, DM, TNM stage, and low KAI1/CD82 levels were potential to be independent prognostic factors for overall survival time (OST) in NSCLC patients.VM and the expression of Notch4, DLL4, and KAI1/CD82 represent promising markers for tumor metastasis and prognosis, and maybe potential therapeutic targets for NSCLC.

Expressions of KAI1 and E-cadherin in nonsmall cell lung cancer and their correlation with vasculogenic mimicry.

BACKGROUND: Metastasis and recurrence are the most common reasons for treatment failure of nonsmall cell lung cancer (NSCLC). Vasculogenic mimicry (VM, new blood supply formation in malignant tumors), E-Cadherin (a calcium-dependent transmembrane glycoprotein that mediates intercellular adhesion), KAI1 (a suppressor gene of tumor metastasis) are all valuable factors for metastasis and prognosis in diverse common human cancers. However, the correlation of VM, E-Cadherin, and KAI1 in NSCLC is still unclear. In this study, we analyzed the correlations among these factors as well as their respective correlations with clinicopathological parameters and survival in NSCLC. METHODS: The level of VM, E-Cadherin, and KAI1 in 163 tissue samples of NSCLC was examined by immunhistochemistry. Clinical data were also collected. RESULTS: Levels of VM was significantly higher, and levels of KAI1 and E-Cadherin significantly lower in NSCLC tissues than in normal lung tissues. Levels of VM were positively associated with lymph node metastasis (LNM), size, grade, and tumor node metastasis (TNM) stages, and negatively associated with patients' overall survival (OS). Levels of KAI1 and E-Cadherin were negatively correlated with LNM, size, grade, and TNM stage, and positively associated with patients' OS. In multivariate analysis, high levels of VM, E-Cadherin, and KAI1, as well as TNM stages were independently correlated with lower OS in patients with NSCLC. CONCLUSION: VM and the expression of E-Cadherin and KAI1 may represent promising metastatic and prognostic biomarkers, as well as potential therapeutic targets for NSCLC.

Vasculogenic mimicry and expression of slug and vimentin correlate with metastasis and prognosis in non-small cell lung cancer.

Background: Non-small cell lung cancer (NSCLC) has been the leading cause of cancer death in recent years, its morbidity and mortality were increasing yearly. The presence of vasculogenic mimicry (VM) is associated with a high tumor grade, short survival, invasion, and metastasis. Slug is a key regulating factor in the process of EMT. Vimentin is one of the cytoskeleton proteins that plays an important role in EMT. However, associations among VM, Slug and vimentin and their clinicopathologic significance in NSCLC are unclear. In this study, we analyzed associations among VM, Slug and vimentin in NSCLC, and their respective associations with clinicopathologic characteristics and survival in NSCLC. Methods: Positive expression of VM, Slug and vimentin in 198 whole NSCLC tissue samples were detected by immunohistochemical staining. Patients' clinical data were also collected. Results: Levels of VM, Slug and vimentin were significantly higher in NSCLC tissues than in normal lung tissues. Levels of VM, Slug and vimentin were positively associated with tumor grade, distant metastasis (DM), lymph node metastasis (LNM), and tumor-node metastasis (TNM) stage, and inversely with patients overall survival time (OST). In multivariate analysis, high expression of VM, Slug, vimentin, and tumor grade, DM, LNM, TNM stage, were potential to be independent prognostic factors for OST in patients with NSCLC. Conclusion: VM, Slug and vimentin affect NSCLC evolution; and the combined detection of VM, Slug and vimentin are valuable factors for metastasis and prognosis in NSCLC patients.

[Expression of vasohibin-1 and MACC1 in lung squamous cell carcinoma and their clinicopathological significance].

OBJECTIVE: To investigate the expressions of vasohibin-1 and MACC1 in lung squamous cell carcinoma (LSCC) and their associations with the clinicopathological characteristics of the patients. METHODS: The expressions of vasohibin-1 and MACC1 proteins were examined with immunohistochemistry in 160 LSCC tissues and 80 normal lung tissues. RESULTS: The positivity rates of vasohibin-1 and MACC1 proteins were 59.4% and 11.3% in LSCC tissues, respectively, which were significantly higher than the rates in normal lung tissues (57.5% and 8.8%, respectively; P<0.05). The expressions of vasohibin-1 and MACC1 proteins were significantly correlated with the tumor grades, lymph node metastasis, and TNM stages (all P<0.05). Spearman correlation analysis indicated a positive correlation between vasohibin-1 expression and MACC1 expressions (P<0.001). Kaplan-Meier survival analysis showed that LSCC patients with a positive expression of vasohibin-1 had significantly shorter overall survival time than those negative for vasohibin-1; the overall survival time was also significantly shorter in patients positive for MACC1 than in those negative for MACC1 (both P<0.05). Multivariate COX regression analysis indicated that positive expressions of vasohibin-1 and MACC1 protein and TNM stage were independent prognostic factors of LSCC. CONCLUSION: Aberrant expressions of vasohibin-1 and MACC1 may participate in the development and promote invasion and metastasis of LSCC. The combined detection of vasohibin-1 and MACC1 expression may provide important evidence for predicting the progression and prognosis of LSCC.