Clinicopathological significances of PLOD2, epithelial-mesenchymal transition markers, and cancer stem cells in patients with esophageal squamous cell carcinoma.

BACKGROUND: To examine the expression level of procollagen-lysine2-oxoglutarate 5-dioxygenase 2 (PLOD2) in esophageal squamous cell carcinoma (ESCC) and analyze its correlation with clinicopathological parameters, in order to explore the mechanism of PLOD2 in regulating invasion and metastasis of ESCC. METHODS: Immunohistochemistry was used to detect the expression level of PLOD2 in tumor tissues and paired adjacent tissues of 172 patients with ESCC, and the relationship between PLOD2 expression and clinicopathological parameters was analyzed. The deposition of collagen fibers in tumor was detected by Sirius red staining. The correlation between tumor stem cells and epithelial-mesenchymal transition (EMT) markers ZEB1 was analyzed by multivariate logistic regression. RESULTS: The expression level of PLOD2 in tumor tissues of patients with ESCC (70.35%, 121/172) was significantly higher than that in paired adjacent tissues (29.65%, 51/172; P < .01). The positive expression rate of PLOD2 in ESCC was related to T classification, lymph node metastasis, and pathological tumor node metastasis of a tumor. The expression rates of ZEB1, CD44, and CD133 in ESCC were correlated with T classification, lymph node metastasis and pathological tumor node metastasis. Scarlet red staining showed that collagen fiber deposition in ESCC tissues with high expression of PLOD2 was significantly higher than that in tissues with low expression of PLOD2 (P < .01). A positive correlation was observed between the expression of PLOD2 and CD133, PLOD2 and CD44, and PLOD2 and N-cadherin (P < .01). Moreover, a negative correlation was noted between the expression of PLOD2 and E-cadherin (P < .01). The combined expression of PLOD2 and ZEB1 were independent prognostic factors for the total survival time of patients with ESCC. CONCLUSION: PLOD2 is highly expressed in ESCC and is closely related to tumor invasion and metastasis. The mechanism of PLOD2 for promoting invasion and metastasis of ESCC may be related to activation of the EMT signaling pathway to promote EMT and tumor stem cell transformation.

Trace metals, polycyclic aromatic hydrocarbons and polychlorinated biphenyls in the surface sediments from Sanya River, China: Distribution, sources and ecological risk.

The urban inland river ecosystems are now facing comprehensive pollution and governance pressures. Up to now, few works related to the multiple pollution assessment of trace metals, polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) for the urban inland river sediments have been reported in China. Our study investigated the spatial distribution, ecological risk and potential sources of trace metals, PAHs and PCBs in surface sediment collected from 20 sampling sites of Sanya River, Hainan Province, China. The pollution status and potential ecological risk of trace metals were evaluated using the contamination indexes including geoaccumulation index (Igeo), individual potential ecological risk (Eri), potential ecological risk index (RI) and pollution load index (PLI). Considering the carcinogenicity and toxicity of PAHs and PCBs to human health and the ecological environment, we also analyzed the distributions, sources and adverse biological effects of PAHs and PCBs according to the sediment quality guidelines (SQGs), principal component analysis (PCA) and other source analysis. This study revealed that the surface sediments in Sanya River were extremely slight pollution and showed a very low ecological risk according to Igeo, Eri, PLI and RI results for trace metals. Besides, PAHs and PCBs pollution detected may not pose considerable adverse biological effect to ecological environment in a foreseeable period on the basis of comprehensive research results. The overall surface sediments quality of the Sanya River not seem to pose a serious pollution and ecological risk based on the evaluation results of multiple pollution factors. The study provided detailed information on the multiple pollution status and location of surface sediments, one of the key environmental indicators of international tourism cities, in the Sanya River, which would be useful for the water quality improvement of Sanya River and the environmental remediation of the other coastal ecosystems from different regions.

Metaplastic breast carcinoma: a retrospective study of 26 cases.

Metaplastic breast carcinoma is a rare invasive breast cancer. Metaplastic breast carcinoma is mainly characterized by an epithelial or mesenchymal cell population mixed with adenocarcinoma. We collected 26 cases of metaplastic breast carcinoma in the First Affiliated Hospital of Bengbu Medical College from 2008 to 2014. Tumor size, tumor grade, vascular invasion, ER/PR status, histologic classification, and HER2/neu status were assessed for all cases and the literature was reviewed. Clinicopathologic characteristics of patients diagnosed with metaplastic breast carcinomas and its key points of differential diagnosis were discussed. All patients were female, with the median age of 50 years. The mean tumor size was 3.2 cm. 4 subtypes of metaplastic breast carcinomas were documented. Fibromatosis-like metaplastic carcinomas are typically characterized by wavy, intertwined, gentle spindle cells. When the tumor components are almost squamous cell carcinoma components and the primary squamous cell carcinoma of other organs and tissues are excluded, we can diagnose breast squamous cell carcinoma. In spindle cell carcinoma, atypical spindle cells are arranged in many ways and are usually accompanied by inflammatory cell infiltrate. Cancer with interstitial differentiation has mixed malignant epithelial and mesenchymal differentiation, and the mesenchymal components are diverse. Most tumors are triple negative. At present, surgical resection combined with chemotherapy or radiation therapy is the most effective and acceptable method for treating metaplastic breast carcinoma.

The microRNA-141-3p/ CDK8 pathway regulates the chemosensitivity of breast cancer cells to trastuzumab.

AIMS: This study was conducted to explore the function of microRNA-141-3p/cyclin-dependent kinase 8 (miR-141-3p/CDK8) in regulating trastuzumab resistance of breast cancer cells. MATERIALS AND METHODS: Microarray analysis was performed to screen microRNAs that are differentially expressed in wild type and trastuzumab-resistant (TR) breast cancer cell lines. TargetScan helped predict the target gene of miR-141-3p. The regulatory relationship was confirmed through a luciferase reporter assay, quantitative reverse transcriptase polymerase chain reaction, and Western blot analysis. The MTT assay, transwell invasion assay, and wound scratch assay were performed to measure the proliferative, invasive, and migratory ability of breast cancer cells, respectively. Tumor cell xenografts in nude mice were conducted to observe the effect of miR-141-3p on trastuzumab resistance in breast cancer cells in vivo. The enzyme-linked immunosorbent assay was used to detect protein secretion. RESULTS: miR-141-3p was downregulated in the drug-resistant cell lines. CDK8 was proved to be a target gene of miR-141-3p. Transfection of miR-141-3p or CDK8 small interfering RNA (siRNA) reversed the resistance to trastuzumab in TR cell lines and suppressed cell invasion and migration. Dysregulation of transforming growth factor beta (TGF-ß) was detected when the expression of CDK8 was silenced by CDK8 siRNA, and downregulation of TGF-ß had a notable effect on reducing the phosphorylation of SMAD2/SMAD3. CONCLUSION: miR-141-3p could restore the sensitivity to trastuzumab in breast cancer cells by repressing CDK8, which might regulate the phosphorylation levels of SMAD2/SMAD3 via TGF-ß.

Correlations of breast cancer FHIT gene with the incidence and prognosis of breast cancer.

PURPOSE: The study aimed to investigate the expression level of fragile histidine triad (FHIT) in breast cancer and analyze its prognostic value. METHODS: 148 patients admitted and definitely diagnosed with breast cancer in Daqing Long Nan Hospital from January 2011 to January 2013 were collected. Breast cancer, cancer-adjacent and normal tissues of the patients were taken and immunohistochemically stained, and the relationship between FHIT and p16 expressions were analyzed at the gene and protein levels. In addition, clinical data of patients were collected, and analyzed if there was a correlation between FHIT and p16 expressions. RESULTS: FHIT and p16 were strongly positive in cancer-adjacent tissues and normal tissues but weakly positive in breast cancer tissues, with statistically significant differences in FHIT and p16 expressions (p<0.05). FHIT expression was positively correlated with p16 expression in breast cancer tissues (Spearman's correlation coefficient r=0.352, p=0.026). There were correlations of FHIT with TNM staging of breast cancer, grade of differentiation, lymph node metastasis and formation of portal vein tumor thrombi (p<0.05 in all comparisons). P16 was correlated with tumor size and grade of differentiation (p<0.05 in all comparisons). Expressions of both FHIT and p16 genes and proteins in breast cancer tissues were remarkably lower than those in cancer-adjacent and normal tissues (p<0.05 in all comparisons). Log-rank analysis showed that the 5-year overall survival of patients with FHIT+p16+expressions was significantly longer than that of patients with other phenotypes of expressions (p<0.0001). CONCLUSION: The tumor suppressor gene FHIT is lowly expressed in breast cancer tissues and positively associated with the expression of the multi-tumor suppressor gene p16. The 5-year overall prognosis of patients with FHIT+p16+ expressions was better and can be used as one of the prognostic indicators for breast cancer patients.

The correlation of the expressions of WWOX, LGR5 and vasohibin-1 in epithelial ovarian cancer and their clinical significance.

BACKGROUND: Recurrence and metastasis are the most common reasons for the treatment failure of epithelial ovarian carcinoma (EOC). WW domain-containing oxidoreductase (WWOX) is a tumor suppressor, which causes down- or lost-expression and is able to promote cell infiltration and progression in several human malignant tumors. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), an important marker of cancer stem cells (CSCs), has been considered a useful biomarker of tumor metastasis and patient prognosis. Vasohibin-1 (VASH1), also known as angiogenesis inhibiting protein-1, can be used as a biological marker for early infiltration and metastasis in many cancers. However, the correlations of WWOX, LGR5, and vasohibin-1 in EOC are still unclear. In this study, we analyzed the relationships of these three markers, as well as their respective correlations with clinicopathological characteristics, to determine whether they are useful biomarkers for the improvement and prognosis of EOC patients. METHODS: The positive rates of WWOX, LGR5, and vasohibin-1 in 210 whole tissue samples of EOC were detected by immunohistochemistry. Clinical data was also collected. RESULTS: The expressions of LGR5 and vasohibin-1 were significantly higher in EOC tissues than the levels in benign ovary tumors. However, WWOX expression was significantly lower in EOC tissues than the levels in benign ovary tumors. The investigation of the associations between WWOX, or LGR5, or vasohibin-1 positive rates with the clinicopathological characteristics of EOC showed associations between the positive rates of each with grade of tumor, lymph node metastasis (LNM), implantation, and International Federation of Gynecology and Obstetrics (FIGO) stage. The overall survival (OS) time of patients with LGR5-positive or vasohibin-1-positive EOC tissues was significantly shorter than that of those who were negative. On the contrary, the OS time of patients with WWOX-positive EOC tissues was significantly higher than the OS time of those who were negative. Importantly, a multivariate analysis indicated that the high level of WWOX, LGR5, and vasohibin-1, as well as implantation, LNM and FIGO stage could be independent prognostic biomarkers for OS in EOC patients. CONCLUSIONS: The expressions of WWOX, LGR5, and vasohibin-1 may represent useful promising biomarkers for metastasis and prognosis, as well as potential therapeutic targets in EOC.

The expression of metastasis-associated in colon cancer-1, Snail, and KAI1 in esophageal carcinoma and their clinical significance.

OBJECTIVE: Metastasis-associated in colon cancer-1 (MACC1) is a key transcriptional regulator of mesenchymal-epithelial transition (MET) gene and so involved in the hepatocyte growth factor/MET signaling pathway. Snail has been reported to be associated with tumor epithelial-mesenchymal transition (EMT) and involved in the process of invasion and metastasis. KAI1 is a suppressor gene of tumor metastasis. The aim of this study is to explore the associations of MACC1, Snail, and KAI1 expression in esophageal squamous cell carcinoma (ESCC) and clinicopathologic characteristics of ESCC patients and their associations with each other. METHODS: Immunohistochemistry was conducted to detect the expression of MACC1, Snail, and KAI1 in 214 whole-ESCC-tissue samples and corresponding normal esophageal mucosa tissues. All clinicopathologic, demographic, and follow-up data were collected. RESULTS: MACC1 and Snail were significantly up-regulated in ESCC samples when compared with control samples; KAI1 was significantly down-regulated in ESCC group when compared with control group. Furthermore, positive expression of MACC1 and Snail was positively associated with tumor stages, lymph-node-metastasis (LNM) stages, and tumor-node-metastasis (TNM) stages. Positive expression of KAI1 was negatively associated with tumor grade, tumor stage, and LNM stages as well as TNM stage. The MACC1- or Snail-positive expression group had more unfavorable overall survival (OS) time than did the MACC1- or Snail-negative group; the positive expression of KAI1 group had significantly longer OS time than did the KiSS-1 negative group. Multivariate analysis of OS showed that overexpression of MACC1 and Snail, and down expression of KAI1 and tumor stages as well as TNM stages were independent prognostic factors for patients with ESCC. CONCLUSIONS: Levels of expression of MACC1, Snail, and KAI1 are associated with the duration of OS in patients with ESCC. MACC1, Snail, and KAI1 should be considered as useful biomarkers and therapeutic targets in ESCC.

[Expression of vasohibin-1, MACC1 and KA11 proteins in serous ovarian cancer and their clinical significance].

OBJECTIVE: To examine the expression of vasohibin-1, metastasis-associated in colon cancer-1 (MACC1) and KAI1 proteins in serous ovarian cancer and their clinical significance.
 Methods: In 124 specimens of serous ovarian cancer (serous ovarian cancer group) and 30 specimens of ovarian serous cystadenoma (ovarian serous cystadenoma group), the expression of vasohibin-1, MACC1 and KAI1 protiens were detected by immunohistochemistry ElivisionTM method.
 Results: In the serous ovarian cancer group, the positive rates of vasohibin-1 and MACC1 proteins were 48.4% and 58.1%, respectively, which were both higher than those in the ovarian serous cystadenoma group (10.0% and 13.3%, respectively); while the positive rate of KAI1 protein in the serous ovarian cancer group was 33.9%, which was lower than that in the ovarian serous cystadenoma group (86.7%), there were significant differences between the 2 groups (all P<0.05). In the serous ovarian cancer group, the expression of the 3 proteins were closely related to the pathological grade, Federation International of Gynecology and Obstetrics (FIGO) stage and pelvic lymph node metastasis (all P<0.05). The KAI1 protein was negatively correlated with the levels of vasohibin-1 and MACC1 (r=-0.500, -0.600, respectively, both P<0.01); while there was a positive correlation between the vasohibin-1 and the MACC1 (r=0.518, P<0.01). Kaplan-Meier survival analysis showed that the over-expression of vasohibin-1, MACC1 and the low-expression of KAI1 protein were related to the survival rates (all P<0.05). Multi-factor analysis showed that the expression of vasohibin-1, KAI1 protein and the FIGO stage were independent prognosis factors for radical operation of serous ovarian cancer (RR=2.185, 3.893, 0.413; 95% CI=1.263-3.779, 2.190-6.921, 0.251-0.681; all P<0.05).
 Conclusion: The up-regulation of vasohibin-1, MACC1 and down-regulation of KAI1 in serous ovarian cancer are related to the tumor differentiation, clinical stage, metastasis and prognosis. Combined detection of these indexes is useful in predicting the progression and prognosis of serous ovarian cancer.

Evaluation of the correlation of MACC1, CD44, Twist1, and KiSS-1 in the metastasis and prognosis for colon carcinoma.

BACKGROUND: Metastasis-associated in colon cancer 1 (MACC1) has been reported to promote tumor cell invasion and metastasis. Cancer stem cells and epithelial-mesenchymal transition (EMT) have also been reported to promote tumor cell proliferation, invasion, and metastasis. KiSS-1, a known suppressor of metastasis, has been reported to be down-regulated in various tumors. However, the associations of MACC1, CD44, Twist1, and KiSS-1 in colonic adenocarcinoma (CAC) invasion and metastasis remain unclear. The purpose of this study is to investigate the roles of MACC1, CD44, Twist1, and KiSS-1 in CAC invasion and metastasis and their associations with each other and with the clinicopathological characteristics of CAC patients. METHODS: Immunohistochemistry and multivariate analysis were carried out to explore the expression of MACC1, CD44, Twist1, and KiSS-1 in 212 whole-CAC-tissue specimens and the corresponding normal colon mucosa tissues. Demographic, clinicopathological, and follow-up data were also collected. RESULTS: The results of this study showed MACC1, CD44, and Twist1 expression to be up-regulated, and KiSS-1 expression was down-regulated in CAC tissues. Positive expression of MACC1, CD44, and Twist1 was found to be positively correlated with invasion, tumor grades, and lymph- node-metastasis (LNM) stages and tumor-node-metastasis (TNM) stages for patients with CAC. Positive expression of KiSS-1 was inversely associated with invasion, tumor size, LNM stage, and TNM stage. The KiSS-1-positive expression group had significantly more favorable OS than did the KiSS-1-negative group. Univariate analysis indicated that overexpression of MACC1, CD44, and Twists1 was negatively associated with longer overall survival (OS) time, and there was a positive relationship between KiSS-1-positive expression and OS time for patients with CAC. Multivariate Cox analysis demonstrated that overexpression of MACC1, CD44, Twist1, and low expression of KiSS-1 and LNM and TNM stages were independent predictors of prognosis in patients with CAC. CONCLUSIONS: The results in this study indicated that levels of expression of MACC1, CD44, Twist1, and KiSS-1 are related to the duration of OS in patients with CAC. MACC1, CD44, Twist1, and KiSS-1 may be suitable for use as biomarkers and therapeutic targets in CAC.

MicroRNA-145 promotes esophageal cancer cells proliferation and metastasis by targeting SMAD5.

OBJECTIVE: To clarify the relative expression and molecular function of microRNA (miR)-145 in esophageal cancer and understand its mechanistic involvement in this disease. MATERIAL AND METHODS: The relative expression of miR-145 in clinical samples was analyzed using the public GSE43732 dataset. The prognostic analysis with respect to miR-145 expression was performed with Kaplan-Meier plot. Cell viability was measured by MTT assay and the anchorage-independent growth was evaluated by soft agar assay. The migration and invasion of esophageal cancer cells were measured using transwell chamber. The regulatory effect of miR-145 on SMAD5 was determined by dual-luciferase reporter assay. The endogenous SMAD5 protein was measured by Western blot. RESULTS: We demonstrated high expression of miR-145 associated with late stage and unfavorable prognosis of esophageal cancer. Ectopic expression of miR-145 mimic significantly stimulated cell proliferation and anchorage-independent growth. Furthermore, high level of miR-145 significantly promoted both migration and invasion in vitro. Notably, we identified SMAD5 as direct target of miR-145, the suppressed expression of which consequently led to increased cell proliferation and migration/invasion. CONCLUSION: Our study uncovered the crucial role of miR-145/SMAD5 in esophageal cancer and highlighted its target potential for diagnostic and therapeutic purpose.

Identification of key gene modules and pathways of human breast cancer by co-expression analysis.

BACKGROUND: Breast cancer is the most common and aggressive tumor causing injury to women world wide. Although gene expression analysis had been performed previously, systemic co-expression analysis for this cancer is still lacking to date. We attempted to identify the critical modules of breast cancer. METHODS: Co-expression modules were established with the help of WGCNA and the interactions among them were performed by R language. Biological process and pathways analysis of co-expression genes were figured out by GO and KEGG functional enrichment analysis using DAVID dataset. RESULTS: In this study, expression data of 4,000 genes from 136 samples with breast cancer was used for the establishment of co-expression modules. And nine modules were identified. There was much higher scale independence among different modules by interactions analysis. Moreover, there was an obvious difference in adjacency degree among different modules. The most enriched pathways as immune response and ubiquitin-mediated proteolysis were identified as the most critical modules of breast cancer by GO and KEGG enrichment analysis. CONCLUSION: Our result demonstrated that immune response and ubiquitin-mediated proteolysis could serve as prognostic and predictive markers for the occurrence of breast cancer, providing evidence for further analysis in the prognosis and treatment of breast cancer.

[Expressions of ΔNp63α, DPC4/Smad4 and P21 in cervical squamous cell carcinoma an their clinical significance].

OBJECTIVE: To investigate the expressions of ΔNp63α, DPC4/Smad4 and P21 in cervical squamous cell carcinomas and explore their implications in tumorigenesis, progression and prognosis of the malignancy. METHODS: The expressions of ΔNp63α, DPC4/Smad4 and P21 were examined with immunohistochemistry in 100 specimens of cervical squamous cell carcinoma, 40 specimens of cervical intraepithelial neoplasia (CIN) and 40 specimens of normal cervical tissues to explore their associations with the occurrence, progression and prognosis of cervical squamous cell carcinoma. RESULTS: The expressions of ΔNp63α and DPC4/Smad4 decreased and P21 expression increased significantly in the order of normal cervical tissue, CIN and cervical squamous cell carcinoma (P < 0.01), and their expressions were associated with the differentiation, clinical stages and lymph node metastasis of cervical squamous cell carcinoma (P < 0.01). The expression of ΔNp63α was positively correlated with the expression of DPC4/Smad4 (r=0.581, P < 0.05), and they were both negatively correlated with P21 expression (r=-0.449 and -0.254, respectively; P < 0.05). Kaplan-Meier survival analysis showed that patients with cervical squamous cell carcinoma positive for ΔNp63α and DPC4/Smad4 had a significantly higher 5-year survival rate than those negative for ΔNp63α and DPC4/Smad4 (P < 0.001); the patients positive for P21 had a significantly lower 5-year survival rate than the P21-negative patients (P < 0.005). CONCLUSIONS: The expressions of ΔNp63α, DPC4/Smad4 and P21are related with the differentiation, invasion, lymph node metastasis, pTNM stage and prognosis of in cervical squamous cell carcinomas, suggesting their value as potential markers for prognostic evaluation of patients with cervical squamous cell carcinoma.

Evaluation of the correlation of vasculogenic mimicry, ALDH1, KAI1 and microvessel density in the prediction of metastasis and prognosis in colorectal carcinoma.

BACKGROUND: Metastasis and recurrence are the most common reasons for treatment failure of colorectal carcinoma (CRC). Vasculogenic mimicry (VM, blood supply formation often seen in highly aggressive tumors), Aldehyde dehydrogenase 1 (ALDH1, a biomarker of cancer stem cells), KAI1 (a suppressor gene of tumor metastasis) are all valuable factors for metastasis and prognosis in diverse human cancers. However, the correlation of VM, ALDH1, KAI1 and microvessel density (MVD) in CRC is unclear. In this study, we analyzed the correlations among VM, ALDH1, KAI1 and MVD, as well as their respective correlations with clinicopathological parameters and survival in CRC. METHODS: The level of VM, ALDH1, KAI1 and MVD in 204 whole tissue samples of CRC were examined by immunhistochemistry. Clinical data was also collected. RESULTS: Levels of VM, ALDH1 and MVD were significantly higher, and levels of KAI1 significantly lower, in CRC tissues than in normal colorectal tissues. Levels of VM, ALDH1 and MVD were positively associated with invasion of depth, lymph node metastasis (LNM), distant metastasis and tumor-node-metastasis (TNM) stages, and negatively with patients' overall survival (OS). Levels of KAI1 was negatively correlated with invasion of depth, LNM, distant metastasis and TNM stages, and the KAI1 positive expression subgroup had significantly longer OS than did the KAI1- subgroup. In multivariate analysis, high levels of VM, ALDH1 and KAI1, as well as TNM stages were independently correlated with lower OS in patients with CRC. CONCLUSIONS: VM, MVD and the expression of ALDH1 and KAI1 may represent promising metastatic and prognostic biomarkers, as well as potential therapeutic targets for CRC.

Evaluation of the correlation of vasculogenic mimicry, ALDH1, KiSS-1, and MACC1 in the prediction of metastasis and prognosis in ovarian carcinoma.

BACKGROUND: Recurrence and metastasis are the usual manifestations of treatment failure of epithelial ovarian carcinoma (EOC). Vasculogenic mimicry (VM; blood supply development often seen in highly aggressive cancers), aldehyde dehydrogenase 1 (ALDH1, cancer stem cell biomarker), KiSS-1 (suppressor of tumor metastasis), and metastasis associated in colon cancer-1 (MACC1) are all useful predictive factors for metastasis and prognosis in various cancers. In this study, we analyzed associations among VM, ALDH1, KiSS-1, and MACC1 in EOC, and their respective correlations with clinicopathological characteristics and survival in EOC. METHODS: Positive rates of VM, ALDH1, KiSS-1, and MACC1 in 207 whole EOC tissue samples were detected by immunohistochemistry. Patients' clinical data were also collected. RESULTS: Levels of VM, ALDH1, and MACC1 were significantly higher, and levels of KiSS-1 significantly lower, in EOC tissues than in benign ovary tumors. Levels of VM, ALDH1, KiSS-1, and MACC1 were associated significantly with tumor/lymph node/metastasis (LNM) grade, implantation, and International Federation of Gynecology and Obstetrics (FIGO) stage, and with patients' overall survival (OS); whereas the KiSS-1+ subgroup had significantly longer OS than did the KiSS-1- subgroup. In multivariate analysis, high VM, ALDH1 or MACC1 levels, FIGO stage, implantation and low KiSS-1 levels were independently associated with shorter OS in patients with EOC. CONCLUSIONS: VM and expressions of ALDH1, KiSS-1, and MACC1 represent promising markers for metastasis and prognosis, and potential therapeutic targets for EOC.

Expression of LGR5 in oral squamous cell carcinoma and its correlation to vasculogenic mimicry.

BACKGROUND: LGR5, also named as GPR49, is considered as a biomarker of cancer stem cells which have been responsible for the initiation, progression, metastasis, and recurrence of cancers. Vasculogenic mimicry (VM) which defines the formation of fluid-conducting tubes by highly progressive and genetically dysregulated cancer cells has been considered as useful biomarker for metastasis and prognosis in various cancers. In this study, we analyzed associations between LGR5 and VM in oral squamous cell carcinoma (OSCC), and their association with clinicopathological characters in OSCC. METHODS: Positive rates of LGR5 and VM in 190 OSCC tissue samples and correspondence normal tissues were detected by immunohistochemical and histochemical staining. Patients' clinical data were also collected. RESULTS: Positive rates of LGR5 and VM were significantly higher in OSCC tissues than those in normal tissues. Positive rates of LGR5 and VM were positively related to tumor size, grades, lymph node metastasis, and TNM stages, and inversely with patients overall survival time. And there was a positive association between the expression of LGR5 and positive rate of VM. In multivariate analysis, high expression of LGR5 and positive VM and lymph node metastasis, as well as TNM stages were to be considered as independent prognosis factors for overall survival time in patients with OSCC. CONCLUSIONS: The expression of LGR5 and VM represent potential biomarkers for metastasis and prognosis, as well as therapeutic targets for OSCC.

Vasculogenic mimicry and expression of Twist1 and KAI1 correlate with metastasis and prognosis in lung squamous cell carcinoma.

BACKGROUND: Vasculogenic mimicry (VM) is a new blood supply development often seen in highly aggressive cancers and has been considered as a usefully metastatic and prognostic factor for many cancers. Twist1 (a biomarker of epithelial-mesenchymal transition), and KAI1 (a suppressor of tumor metastasis) are both usefully predictive factors for metastasis in many cancers. However, the metastatic and prognostic value of VM, Twist1, or KAI1 in lung squamous cell carcinoma (LSCC) is unclear. In this study, we analyzed associations among VM, Twist1, and KAI1 in LSCC, and their respective associations with clinicopathological parameters and survival in LSCC. CASE PRESENTATION: Positive rates of VM, Twist1, and KAI1 in 157 whole LSCC tissue specimens were detected by immunohistochemistry and histochemical staining. Patient's clinical data were also collected. Levels of VM and Twist1 were significantly higher, and levels of KAI1 were significantly lower, in LSCC tissues than in normal lung tissues. Levels of VM and Twist1 were positively associated with tumor grade, lymph node metastasis (LNM), and tumor-node-metastasis (TNM) stage, and inversely with patients overall survival (OS) time; levels of KAI1 was negatively associated with tumor grade, LNM, and TNM stage, and the KAI1+ subgroup had significantly longer OS time than did the KAI1- subgroup. In multivariate analysis, high VM, or Twist1 levels, TNM stage, size of tumors, and low KAI1 levels were potential to be independent prognostic factors for OS time in patients with LSCC. CONCLUSIONS: VM, and the expression of Twist1 and KAI1 represent promising markers for metastasis and prognosis, and potential therapeutic targets for LSCC.

Expression of ORAOV1, CD133 and WWOX correlate with metastasis and prognosis in gastric adenocarcinoma.

BACKGROUND: Oral cancer overexpressed 1 (ORAOV1) which is a novel candidate oncogene is a useful biomarker of metastasis and prognosis in various cancers. CD133 which is a biomarker of cancer stem cells is overexpressed in many cancers and promotes cancer cells growth and metastasis. WW domain-containing oxidoreductase (WWOX) which is a suppressor gene of tumor can inhibit proliferation and promote apoptosis in various cancers. However, associations among ORAOV1, CD133, and WWOX and their clinicopathological significance in gastric adenocarcionma (GAC) are unclear. In this study, we analyzed associations among ORAOV1, CD133, and WWOX in GAC, and their respective associations with clinicopathological characteristics and survival in GAC. METHOD: Positive expression of ORAOV1, CD133, and WWOX in 236 whole GAC tissue samples were detected by immunohistochemistry staining. Patients' clinical data were also collected. RESULTS: Levels of ORAOV1 and CD133 were significantly higher, and levels of WWOX significantly lower, in GAC tissues than in normal gastric tissues. Levels of ORAOV1 and CD133 were positively associated with tumor grade, invasion of depth, lymph node metastasis (LNM), and tumor-node metastasis (TNM) stages, and inversely with patients overall survival time; levels of WWOX was negatively correlated with tumor grade, invasion of depth, LNM, and TNM stages, and the WWOX-positive subgroup had significantly longer overall survival time than did the WWOX-negative subgroup. In multivariate analysis, high expression of ORAOV1 and CD133, invasion of depth, and TNM stages, and low expression of WWOX were potential to be independent prognostic factors for overall survival time in patients with GAC. CONCLUSIONS: The expression of ORAOV1, CD133, and WWOX represent promising biomarkers for metastasis and prognosis, and potential therapeutic targets for GAC.

Metastasis-associated in colon cancer-1 and aldehyde dehydrogenase 1 are metastatic and prognostic biomarker for non-small cell lung cancer.

BACKGROUND: Tumor recurrence and metastasis are the most common reason for treatment failure. Metastasis-associate in colon cancer-1 (MACC1) has been identified as a metastatic and prognostic biomarker for colorectal cancer and other solid tumors. Aldehyde dehydrogenase 1 (ALDH1), a marker of cancer stem cells, is also associated with metastasis and poor prognosis in many tumors. However, the prognostic value of either MACC1 or ALDH1 in non-small cell lung cancer (NSCLC) is unclear. In this study, we explored the relationship between MACC1 and ALDH1 expression, as well as their respective associations with clinicopathological features, to determine if either could be useful for improvement of survival prognosis in NSCLC. METHODS: The expression levels of both MACC1 and ALDH1 in 240 whole tissue sections of NSCLC were examined by immunohistochemistry. Clinical data were also collected. RESULTS: MACC1 and ALDH1 were significantly overexpressed in NSCLC tissues when compared to levels in normal lung tissues. Investigation of associations between MACC1 or ALDH1 protein levels with clinicopathological parameters of NSCLC revealed correlations between the expression of each with tumor grade, lymph node metastasis, and tumor node metastasis. The overall survival of patients with MACC1- or ALDH1-positive NSCLC tumors was significantly lower than that of those who were negative. Importantly, multivariate analysis suggested that positive expression of either MACC1 or ALDH1, as well as TNM stage, could be independent prognostic factors for overall survival in patients with NSCLC. CONCLUSIONS: MACC1 and ALDH1 may represent promising metastatic and prognostic biomarkers, as well as potential therapeutic targets, for NSCLC.

The expression of metastasis-associated in colon cancer-1 and KAI1 in gastric adenocarcinoma and their clinical significance.

BACKGROUND: The most common reason for malignant tumor treatment failure is recurrence and metastasis. Metastasis-associated in colon cancer-1 (MACC1) was originally identified as a metastatic and prognostic biomarker for colon cancer and later other solid tumors. Kangai 1 (KAI1), a marker of suppressor of metastasis, is also associated with metastasis and poor prognosis in many tumors. However, the prognostic value of either MACC1 or KAI1 in gastric adenocarcinoma (GAC) is unclear. In this study, we explored the relationship between MACC1 and KAI1 expression, as well as their respective correlation with clinicopathological features, to determine if either could be helpful for improvement of survival prognosis in GAC patients. METHODS: The expression levels of both MACC1 and KAI1 in 325 whole-tissue sections of GAC were examined by immunohistochemistry. Clinical data was also collected. RESULTS: MACC1 was significantly overexpressed in GAC tissues when compared to levels in normal gastric tissues; KAI1 was significantly down-expressed in GAC tissues when compared to levels in normal gastric tissues. Investigation of association between MACC1 and KAI1 protein levels with clinicopathological parameters of GAC indicated association between the expression of each with tumor grade, lymph node metastasis, invasive depth, and TNM stages. The overall survival time of patients with MACC1- or KAI1-positive GAC tumors was significantly shorter or longer than that of those who were negative. Importantly, multivariate analysis suggested that positive expression of either MACC1 or KAI1, as well as TNM stage, could be independent prognostic factors for overall survival in patients with GAC. CONCLUSIONS: MACC1 and KAI1 may represent promising metastatic and prognostic biomarkers, as well as potential therapeutic targets, for GAC.

[Expressions of OCT4, Notch1 and DLL4 and their clinical implications in epithelial ovarian cancer].

OBJECTIVE: To investigate the correlations among OCT4, Notch1 and DLL4 and their association with the clinicopathological features of patients with epithelial ovarian cancer (EOC). METHODS: A total of 207 specimens of EOC and 65 specimens of benign ovarian epithelial tumor tissues were examined for expressions of OCT4, Notch1 and DLL4 proteins using immunohistochemistry. RESULTS: The positivity rates of OCT4, Notch1 and DLL4 in EOC tissues were 60.0%, 61.8% and 60.9%, respectively, significantly higher than the rates in benign epithelial tumor tissues (9.2%, 6.2%, and 0, respectively; P<0.05). The expressions of OCT4, Notch1 and DLL4 in EOC were significantly correlated with tumor differentiation, FIGO stage, and lymph node metastasis (P<0.05). DLL4 was positively correlated with OCT4 and Notch1 expressions (r=0.758 and 0.704, respectively, P<0.001), and the latter two were also positively correlated (r=0.645, P<0.001). Overexpressions of OCT4, Notch1 and DLL4 were associated with a poor prognosis, and the survival rate was significantly lower in patients positive for OCT4, Notch1, and DLL4 than in the negative patients (P<0.05). FIGO stage and expressions of OCT4 and DLL4 were independent prognostic factors of EOC (P<0.05). CONCLUSION: The expressions of OCT4, Notch1 and DLL4 are correlated with the differentiation, lymph node metastasis, clinical stage and prognosis of EOC. Combined detection of the 3 proteins has an important value in predicting the progression and prognosis of EOC.