The Emerging Role of Sperm-Associated Antigen 6 Gene in the Microtubule Function of Cells and Cancer.

Accumulated evidence shows that sperm-associated antigen 6 (SPAG6) gene has multiple biological functions. It maintains the normal function of a variety of cells including ciliary/flagellar biogenesis and polarization, neurogenesis, and neuronal migration. Moreover, SPAG6 is found to be critically involved in auditory transduction and the fibroblast life cycle. Furthermore, SPAG6 plays an essential role in immuno-regulation. Notably, SPAG6 has been demonstrated to participate in the occurrence and progression of a variety of human cancers. New evidence shows that SPAG6 gene regulates tumor cell proliferation, apoptosis, invasion, and metastasis. Therefore, in this review, we describe the physiological function and mechanism of SPAG6 in human normal cells and cancer cells. We also highlight that SPAG6 gene may be an effective biomarker for the diagnosis of human cancer. Taken together, targeting SPAG6 could be a novel strategy for the treatment of human diseases including cancer.

Xp11.2 translocation/TFE3 gene fusion renal cell carcinoma with a micropapillary pattern: cases report and literature review.

Xp11.2 translocation/transcription factor E3 (TFE3) gene fusion renal cell carcinoma (Xp11.2 translocation RCC) was first classified as a distinct type of renal tumor by the World Health Organization in 2004. However, its morphology and clinical manifestations often overlap with those of conventional RCCs. Moreover, a micropapillary pattern (MPP) comprising small papillary cell clusters surrounded by lacunar spaces has never been described in RCC. We compared the clinicopathological and prognostic characteristics of one patient with Xp11.2 translocation RCC exhibiting an MPP (TFE3-M) to those of four patients with conventional Xp11.2 translocation RCC (TFE3-N); all five tumors resembled conventional RCCs on gross pathology. All patients exhibited similar histologies, clinical manifestations, and prognoses, and all underwent radical nephrectomy. However, their characteristics differed significantly from those of other MPP-comprising neoplasms. Both tumor types were positive for TFE3 and vimentin; however, TFE3-M tumor cells expressed epithelial membrane antigen and human melanoma black-45 but not cluster of differentiation 10 (CD10), whereas the TFE3-N cells expressed P504S, CD10, and vimentin but not cytokeratin 7. Our RT-PCR analysis result showed that TFE3-N and TFE3-M tumor cells were identified expressing ASPSCR1-TFE3 and PRCC-TFE3 fusion genes, respectively. These findings suggest that TFE3-M should be classified as a histological subtype of Xp11.2 translocation RCC, although its relationship with other MPP-exhibiting neoplasms remains unclear. The histological characteristics of Xp11.2 translocation RCCs depend on MiT family transcription factors and their gene fusion partners. Xp11.2 translocation RCC should be considered for malignancies presenting with a particular pattern; such malignancies can be identified reliably by their morphological and immunohistochemical profiles.

WISP2 exhibits its potential antitumor activity via targeting ERK and E-cadherin pathways in esophageal cancer cells.

BACKGROUNDS: Emerging evidence has demonstrated that WISP2 is critically involved in cell proliferation, migration, invasion and metastasis in cancers. However, the function of WISP2 in esophageal squamous cell carcinoma (ESCC) is largely unclear. Therefore, we aim to explore the effects and the potential mechanism of WISP2 on proliferation and motility and invasion of ESCC cells. METHODS: Cell proliferation was detected by MTT assay and apoptosis was measured by FACS in ESCC cells after WISP2 downregulation and overexpression. Cell migration and invasion were analyzed by wound healing assay and transwell migration assay, respectively. The expression of ERK-1/2, Slug and E-cadherin was measured by Western blot respectively. IHC was performed to measure the expression of WISP2 in ESCC tissues. RESULTS: WISP2 overexpression is associated with survival in ESCC patients. WISP2 overexpression inhibited cell growth and induced cell apoptosis, suppressed cell migration and invasion in ESCC cells. Moreover, WISP overexpression retarded tumor growth in mouse model. WISP2 downregulation enhanced cell growth, inhibited apoptosis, promoted cell migration and invasion in ESCC cells. Mechanistically, WISP2 exerts its tumor suppressive functions via regulation of ERK1/2, Slug, and E-cadherin in ESCC cells. CONCLUSIONS: Our findings suggest that activation of WISP2 could be a useful therapeutic strategy for the treatment of ESCC.

[Expression of AXIN and MACC1 in Gastric Carcinoma and Its Clinical Significance].

OBJECTIVE: To investigate the expression of axis inhibition protein (AXIN) and metastasis-associated in colon cancer-1 (MACC1) in gastric carcinoma and their relationship to the clinicopathologic characteristics. METHODS: Expressions of AXIN and MACC1 proteins were examined by immunohistochemistry containing 100 specimens of gastric tissues (gastric carcinoma group) and 60 specimens of normal gastric mucosa tissues (control group,the nearby tissues of the excised specimen of gastric cancer patients,from the tumor of the gastric cancer >5.0 cm,and confirm that there were no cancer cells). RESULTS: The positive rates of AXIN and MACC1 proteins in gastric carcinoma and the control tissues were 37.0% vs. 83.3% and 58.0% vs. 6.7%,respectively. The difference were significant between the two groups (both P<0.05). The expressions of AXIN and MACC1 proteins were significantly related with grades of tumor,depth of invasion,lymph node metastasis,and Duke stages ( P<0.05). Spearman analysis showed that there was a negative relationship between the AXIN expression and MACC1 expression (r=-0.355, P<0.05). Kaplan-Meier survival analysis and log-rank single factor analysis showed that AXIN and MACC1 protein expressions were related to the 5-year survival rate of patients (both P<0.05). Cox regression analysis showed that the positive expression of AXIN and the negative expression MACC1 protein,and Duke stages (Ⅲ-Ⅳ) were the independent prognostic factors of gastric carcinoma. CONCLUSION: The expressions of AXIN and MACC1 proteins are related to the prognosis of gastric carcinoma patients,and are involved in the invasion and metastasis of gastric carcinoma.

[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.

[Expressions of Slug, ZEB1 and KISS-1 in gastric adenocarcinoma and their clinical significance].

OBJECTIVE: To identify potential markers for predicting invasion, metastasis, and prognosis of gastric adenocarcinoma (GAC). METHODS: The expressions of Slug, ZEB1 and KISS-1 were detected immunohistochemically in 261 GAC tissues and 80 normal gastric tissues. RESULTS: The positivity rates of Slug, ZEB1, and KISS-1 in gastric tissues were 2.5%, 1.3%, and 87.5%, respectively, significantly different from the rates of 62.1%, 28.4%, and 41.1% in GAC tissues (P<0.05). The expression level of Slug was significantly correlated with the depth of invasion, lymph node metastasis, and pTNM stages; the positivity rates of both ZEB1 and KISS-1 were significantly correlated with the tumor grade, depth of invasion, lymph node metastasis and pTNM stages. Slug expression was positively correlated with ZEB1 expression, and KISS-1 expression was inversely correlated with Slug and ZEB1 expressions. Kaplan-Meier analysis showed that the overall survival time of patients with positive expressions of Slug and ZEB1 was significantly shorter than that of the negative patients, and the survival time of patients positive for KISS-1 was significantly longer than the negative patients. COX multivariate analysis showed that positive Slug, ZEB1 and KISS-1 protein expressions and pTNM stages were independent prognostic factors of GAC (P<0.05). CONCLUSION: The abnormal expressions of Slug, ZEB1 and KISS-1 may contribute to the tumorigenesis of GAC and are related with lymph node metastasis, pTNM stages, and prognosis of GAC. The combined detection of Slug, ZEB1, and KISS-1 expression has an important value in predicting the progression and prognosis of 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.

Aberrant Expression of Markers of Cancer Stem Cells in Gastric Adenocarcinoma and their Relationship to Vasculogenic Mimicry.

BACKGROUND: Gastric cancer is the second leading cause of cancer-related death in Asia, and the majority type is gastric adenocarcinoma (GAC). Most GAC patients die of recurrence and metastasis. Cancer stem cells (CSCs) have been thought to be responsible for the initiation, development, metastasis, and ultimately recurrence of cancer. In this study, we aimed to investigate expression and clinical significance of CSCs markers, CD133 and Lgr5, and vasculogenic mimicry (VM) in primary GAC. MATERIALS AND METHODS: Specimens from 261 Chinese patients with follow-up were analyzed for CD133, Lgr5 protein expression and VM by immunohistochemical and histochemical staining. The Pearson Chi's square test was used to assess the associations among the positive staining of these markers and clinicopathological characteristics. Postoperative overall survival time was were studied by univariate and multivariate analyses. RESULTS: In GAC tissues, positive rates of 49.0%, 38.7%, and 26.8% were obtained for CD133, Lgr5, and VM, respectively. The mean score of microvessel density (MVD) was 21.7±11.1 in GAC tissues. There was a significantly difference between the positive and negative groups. There was a positive relationship between the VM, the expression of CD133 and Lgr5, and the score of MVD and the grades of tumor, lymph node metastasis, TNM stages (all p<0.05). The overall mean survival time of the patients with CD133, Lgr5, VM, and MVD (≥22) positive expression was lower than that of patients with negative expression. The score of MVD, positive expression of CD133 and VM were independent prognostic factors of GAC (p<0.05). CONCLUSIONS: VM, and expression of CD133, Lgr5, and the score of MVD are related to grades of tumor, lymph node metastasis, TNM stages, and overall mean survival time. It is suggested that CSCs and VM could play an important role in the evolution of GAC.

[The expression of KAI1 in gastric adenocarcinoma and relationship with angiogenesis/lymphangiogenesis].

OBJECTIVE: To seek good markers to predict invasion and metastasis of gastric adenocarcinoma (GAC). METHODS: Expression of Kangai 1 (KAI1), CD34, and D2-40 were examined by immunohistochemistry containing 145 specimens of GAC and 50 specimens of normal gastric tissue. Microvessel density (MVD) and lymph vessel density (LVD) were determined by the mean number of small CD34-positive or D2-40-positive vessels counted. And the relationship of KAI1, MVD and LVD, as well as the role of them on invasion, metastasis and prognosis in GAC were analyzed. RESULTS: The positive rate of KAI1, the median scores of MVD and LVD in normal gastric tissue and GAC tissue were 92.0%, (9.2 +/- 7.8)/LP, (7.5 +/- 7.6)/LP and 37.2%, (21.6 +/- 9. 1)/ LP, (22.6 +/- 12.7)/LP, respectively. And there was a significant different between the two groups (P < 0.05). The expression of KAI1, the scores of MVD and LVD were significantly related with pathologic-tumor-node metastasis (pTNM) stages, depth of invation and lymph node metastasis (all P < 0.05). There was a significant relationship between the expression of KAI1 and the scores of MVD or LVD. The survival rate of the KAI1-positive or KAI1-negative group was significantly different (P < 0.01); the survival rates were significantly lower in MVD > or = 22's group than that in MVD < 22's group, so was the same relationship between the LVD > or = 23's group and the LVD < 23's group (both P < 0.01). Cox regression analysis: pTNM stage, expression of KAI1, and the scores of MVD were independent factors of postoperative survival time in GAC (P < 0.05). CONCLUSION: The combined detection of KAI1, CD34, and D2-40 has an important role in predicting the progression and prognosis of GAC.

[Expression of Gal-3 and CD82/KAI1 proteins in non-small cell lung cancer and their clinical significance].

OBJECTIVE: To study the expression of galectin 3 (Gal-3) and CD82/KAI1 proteins in non-small cell lung cancer (NSCLC) and the correlation between their expression and clinical significance. METHODS: The expression of Gal-3 and CD82/KAI1 proteins was detected by immunohistochemistry in 160 specimens of NSCLC and 20 specimens of normal lung tissue. RESULTS: The positive rates of Gal-3 and CD82/KAI1 proteins in the NSCLC were 63.8% and 37.5%, respectively, the positive rates of Gal-3 and CD82/KAI1 proteins in the normal lung tissue were 25.0% and 95.0%, respectively, and there was a significant difference between the two groups (P < 0.01). The expression of Gal-3 and CD82/KAI1 proteins was significantly correlated with the grade of tumor, lymph node metastasis, and pathological-TNM stages (all P < 0.05). Spearman analysis showed that there was a negative correlation between expressions of Gal-3 and CD82/KAI1 in NSCLC (r = -0.732, P < 0.01). Overexpression of Gal-3 and low expression of CD82/KAI1 were related to poor prognosis: the survival rate was significantly lower in the positive Gal-3 group (survival time: 23.0 ± 17.5 months) than that in the negative group (survival time: 71.6 ± 21.6 months) (P < 0.01). The survival rates of the CD82/KAI1-positive group (survival time: 72.5 ± 19.5 months) and CD82/KAI1-negative group (survival time: 21.6 ± 16.1 months) were significantly different (P < 0.01). Multivariate analysis indicated that pTNM stage and positive expression of Gal-3 and CD82/KAI1 are independent prognostic factors of NSCLC (P < 0.01). CONCLUSIONS: The expression of Gal-3 and CD82/KAI1 may be related to the initiation, development and metastasis of NSCLC. Combined detection of Gal-3 and CD82/KAI1 has an important role in predicting the progression and prognosis of NSCLC.

[Correlation between bacterial L-form infection, expression of HIF-1α/MMP-9 and vasculogenic mimicry in epithelial ovarian cancer].

The aim of the present study is to explore whether vasculogenic mimicry (VM) and bacterial L-form infection exist in human epithelial ovarian cancer (EOC) or not and to elucidate the correlation of L-form infection, expression of hypoxia inducible factor 1α (HIF-1α)/MMP-9 and VM. In 87 specimens of EOC and 20 specimens of ovarian benign epithelial tumor tissues, L-form infection was detected by Gram's staining, expression of HIF-1α/MMP-9 and VM were detected by immunohistochemical and histochemical staining. The results showed that the positive rates of HIF-1α and MMP-9 protein in EOC were 52.9% and 66.7%, while in benign epithelial tumor tissues, the positive rates were 10.0% and 10.0% respectively, and there were significant differences between them (P < 0.05). In EOC and benign epithelial tumor tissues, L-form infections ratios were 24.1% and 0, respectively, and the difference was also significant (P < 0.01). Expression of VM, HIF-1α and MMP-9 in EOC was significantly related to differentiation, abdominal implantation and lymph node metastasis and FIGO stage (P < 0.01). L-form infection had relationship with abdominal implantation, lymph node metastasis and FIGO stage (P < 0.01 or 0.05). The expression of HIF-1α had positive relationship with expression of MMP-9 and VM (r = 0.505, 0.585, respectively, P < 0.01); there was also a positive relationship between MMP-9 expression and VM (r = 0.625, P < 0.01). Overexpression of VM, HIF-1α and MMP-9 were related to poor prognosis: the survival rates were significantly lower in positive patients than those in negative patients (P < 0.05). And the group with L-form infection also had poor prognosis: the survival rates were lower than those in group without infection (P < 0.05). FIGO stage, expression of VM, HIF-1α and MMP-9 were independent prognosis factors of EOC (P < 0.05). The results suggest that L-form infection, the expression of HIF-1α, MMP-9 and VM in EOC are related to differentiation, lymph node metastasis, clinical stage and prognosis. Combined detection of these indexes has an important role in predicting the progression and prognosis of EOC.