Role of Paip1 on angiogenesis and invasion in pancreatic cancer.

Poly(A)-binding protein-interacting protein 1 (Paip1) was discovered as a modulator of translation initiation as a result of binding to PABP. Increasing evidence suggested that Paip1 has been implicated in several pathogenic roles. However, its clinical significance and underlying molecular mechanisms in Pancreatic cancer (PC) remain uncertain. In our present study, we found that Paip1 was over-expressed in human PC tissues. As well as poor survival, the over-expression of Paip1 was associated with lymph node (LN) metastasis of the PC samples analyzed. Paip1 silencing inhibits PC cell proliferation, metastasis, and angiogenesis, whereas over-expression of Paip1 produces the opposite effects. In all, we proposed that Paip1 contributes to PC progression and appears to be a valid prognostic factor of PC.

NAD(P)H:quinone oxidoreductase-1 overexpression predicts poor prognosis in small cell lung cancer.

NAD(P)H: quinone oxidoreductase-1 (NQO1) is commonly elevated in various types of human cancers, including pancreatic, breast and thyroid cancer, as well as others. However, little is known concerning the status of NQO1 in small cell lung cancer (SCLC). To investigate the clinicopathological significance of NQO1 expression and evaluate its role as a potential prognostic marker in SCLC, protein and mRNA expression levels of NQO1 were determined in four fresh tissue samples of SCLC and paired adjacent non-cancerous tissues using western blotting and real-time qRT-PCR, respectively, and 115 cases of SCLC with strict follow-up were selected for immunohistochemical (IHC) staining of NQO1 protein. The correlation between NQO1 expression and the clinicopathological features of SCLC was evaluated using the Chi-square (χ2) and Fisher's exact tests, survival rates were calculated using the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox proportional hazards regression model. In regards to the results, levels of NQO1 protein and mRNA were significantly elevated in the four fresh tissue samples of SCLC compared with levels in the paired adjacent non-cancerous tissues, respectively. IHC analysis showed that the rate of strong positive NQO1 protein expression was significantly higher (48.70%) in SCLC when compared with the rate in either adjacent non-cancerous or normal lung tissues (both P<0.001). The rate of strong positive NQO1 protein expression was correlated with large tumor size (P=0.019), late pathologic stage (P=0.001) and the presence of lymph node metastasis (P=0.001). Moreover, high­level expression of NQO1 protein was significantly correlated with lower disease-free survival (P=0.001) and 5-year survival rates (P<0.001) in SCLC patients, particularly early­stage patients (P=0.045 and P=0.033, respectively). Further Cox analysis revealed that NQO1 expression emerged as a significantly independent hazard factor for the 5-year survival rate of patients with SCLC (P=0.042). In conclusion, NQO1 plays an important role in the progression of SCLC, and it may potentially be used as a biomarker and therapeutic target of SCLC.

High expression of oncoprotein DEK predicts poor prognosis of small cell lung cancer.

Oncoprotein DEK plays an important role in cancer tumorigenesis. To explore the clinical implication of DEK expression on prognostic evaluation in small cell lung cancer (SCLC), 130 cases of SCLC with strict follow-up were selected for immunohistochemical (IHC) staining of DEK protein. The correlation between DEK expression and clinicopathological features of SCLC was evaluated using the Chi-square and Fisher's exact tests, survival rates were calculated using the Kaplan-Meier method and univariate and multivariate analyses were performed using the Cox proportional hazards regression model. IHC analysis demonstrated that DEK protein staining was strongly positive and significantly higher (44.62%) in SCLC compared with either adjacent non-tumor or normal lung tissues (P < 0.001 for both). DEK expression correlated with large tumor size (P = 0.025) and late pathologic stage (P = 0.005). Moreover, it correlated with low disease-free (P = 0.004) and 5-year (P = 0.005) survival rates. In the late-stage group, disease-free and 5-year survival rates of patients with high level DEK expression were significantly lower than those with low level DEK expression (P = 0.006 and P = 0.001, respectively). Furthermore, Cox analysis revealed that DEK expression emerged as a significant independent hazard factor for the overall survival rate of patients with SCLC (HR: 1.594, 95% CI: 1.087-2.336, P = 0.017). In conclusion, DEK plays an important role in the progression of SCLC. DEK may potentially be used as an independent biomarker for the prognostic evaluation of SCLC.

High expression of leucine zipper-EF-hand containing transmembrane protein 1 predicts poor prognosis in head and neck squamous cell carcinoma.

Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is a mitochondrial inner membrane protein and plays an important role in mitochondrial ATP production and biogenesis. High expression levels of LETM1 have been correlated with numerous human malignancies. This study explored the clinicopathological significance of LETM1 expression as a prognostic determinant in head and neck squamous cell carcinoma (HNSCC). HNSCC samples from 176 patients were selected for immunohistochemical staining of LETM1 protein. Correlations between LETM1 overexpression and clinicopathological features of HNSCC were evaluated by Chi-squared tests and Fisher's exact tests, and relationships between prognostic factors and patient survival were analyzed using Cox proportional hazards models. Our results demonstrated that the strongly positive rate of LETM1 protein was 65.3% in HNSCC, which was significantly higher than in either adjacent nontumor tissue (25.0%) or normal squamous epithelia (6.7%). LETM1 overexpression correlated with poor differentiation, presence of lymph node metastasis, advanced stage, absence of chemoradiotherapy, and 5-year disease-free survival and overall survival rates in HNSCC. Further analysis showed that high LETM1 expression, advanced stage, and nonchemoradiotherapy were significant independent risk factors for mortality in HNSCC. In conclusion, LETM1 plays an important role in the progression of HNSCC and is an independent poor prognostic factor for HNSCC.

Sineoculis homeobox homolog 1 protein overexpression as an independent biomarker for pancreatic ductal adenocarcinoma.

Sineoculis homeobox homolog 1 (SIX1) is a member of the SIX gene family. It is highly expressed in cancers derived from tissues that play a fundamental role during embryogenesis. Recent studies suggest that inappropriate expression of SIX1 can both initiate tumorigenesis and promote metastasis. To investigate the clinicopathological significance of SIX1 expression in pancreatic ductal adenocarcinoma (PDAC), and to further identify its role as a potential biomarker and therapeutic target in PDAC, 103 PDAC tissue samples and 45 normal pancreatic tissue samples were immunohistochemically stained for SIX1 protein. The localization of SIX1 protein was detected in Panc-1 cancer cells using immunofluorescence staining. Correlations between SIX1 overexpression and the clinicopathological features of pancreatic cancer were evaluated using Chi-square (χ(2)) tests, differences in survival curves were analyzed using log-rank tests, and multivariate survival analysis was performed using the Cox proportional hazard regression model. In results, SIX1 protein showed mainly cytoplasmic/perinuclear staining pattern in PDAC with immunohistochemistry. The strongly positive rate of SIX1 protein was 60.2% (62/103) in PDAC, which was significantly higher than normal pancreatic tissue (6.7%, 3/45). SIX1 overexpression was positively correlated with tumor size, TNM stage, lymph node metastasis, and grade of PDAC (P < 0.001). SIX1 high expression levels influenced overall survival rates in G1, G2, stage I-II and stage III-IV groups of PDAC; and high expression levels had significantly lower overall survival rates than SIX1 low expression levels. In conclusion, SIX1 emerged as a significant independent prognostic factor in PDAC. SIX1 overexpression appears to be associated with PDAC, and may be a potential biomarker for early diagnosis and prognostic evaluation of PDAC.

DEK overexpression is correlated with the clinical features of breast cancer.

To investigate the clinicopathological significance of DEK overexpression in breast cancers, a total of 196 cases, including 20 of normal tissues, 12 of intraductal hyperplasia, 31 of ductal carcinoma in situ (DCIS) and 133 of invasive ductal carcinoma of the breast, were selected from the Department of Pathology, Yanbian Tumor Hospital for immunohistochemical staining of DEK, estrogen (ER), progesterone (PR) and Ki-67 proteins. In results, DEK protein had higher positivity in DCIS, compared with the adjacent normal breast tissues. Also, DEK protein was strongly positive in invasive ductal carcinoma of the breast on immunohistochemistry, which was significantly higher than normal breast tissues. However, only two (2/12) cases of intraductal hyperplasia of the breast showed positive staining for DEK protein. Additionally, DEK overexpression was significantly correlated with the increased proliferating index of Ki-67. For the histological grade, DEK positive rate was only 39.6% in G1 breast cancers, but significantly higher in G2 (92.3%) and G3 (97.0%) cases (P<0.05). Also, a strongly positive rate of DEK was lower in Stage-0 (21.4%) and Stage-I (40.9%) compared with Stage-IIa (87.5%), Stage-IIb (89.7%) and Stage-IIIa (92.3%) (P<0.05). And DEK protein showed higher expression level in < 3 years disease free survival breast cancers than it did in ≥ 3 years disease free survival cases (P<0.05). However, no statistically difference was found among DEK expression, lymph node metastasis, and ER and PR expressions. In conclusion, DEK overexpression appears to be associated with breast cancer progression and DEK may potentially be used as a breast cancer biomarker for the early diagnosis, prognostic evaluation and therapeutic target for breast cancer.

DEK overexpression in uterine cervical cancers.

The purpose of the present paper was to investigate the significance of DEK protein expression in uterine cervical lesions and its relationship with HPV infection status. DEK protein expression was studied in 253 cervical lesions, including 30 non-neoplastic cervix with or without squamous metaplasia, 64 cervical intra-epithelial neoplasias (CIN; CIN-1, n = 28; CIN-2, n = 17; CIN-3, n = 19), 102 squamous cell carcinomas (SCC), 51 adenocarcinomas, and six adenosquamous cell carcinomas (adenoSCC) on immunohistochemistry. For comparison, HPV-positive and -negative cervical cancer cell lines were also included. The HPV screening was performed using TaKaRa polymerase chain reaction. On immunohistochemistry DEK was found to be negative in all 30 non-neoplastic cervical epithelia, but it was positive in 96.1% of SCC (98/102), 92.2% of adenocarcinomas (47/51), 100% of adenoSCC (6/6), 85.7% of CIN-1 (24/28), 94.1% of CIN-2 (16/17), and 89.5% of CIN-3 (17/19). There was no significant difference between HPV-positive and -negative cervical lesions. Also, strongly positive staining was observed in all aforementioned cervical cancer cell lines regardless of HPV infection, according to immunocytochemistry. In summary, DEK plays an important role in the carcinogenesis of cervical cancers, and can be helpful for early diagnosis, and is a potential therapeutic target.

DeltaNp63 protein expression in uterine cervical and endometrial cancers.

PURPOSE: To investigate the significance of p63 expression in uterine cervical and endometrial cancers. MATERIALS AND METHODS: DeltaNp63 protein expression was studied in a variety of 127 cases of uterine cervical lesions (20 non-neoplastic cervices, 43 cervical intraepithelial neoplasia [CIN], 54 squamous cell carcinomas (SCCs), 40 adenocarcinomas, and 13 other histologic types) and 30 endometrioid type of endometrial adenocarcinomas by using immunohistochemistry. One SCC cell line (ME-180) and one adenocarcinoma cell line (HeLa) were also included. RESULTS: In uterine cervix, the expression of DeltaNp63 was increased with progression of CIN, and positive in all SCCs, transitional cell carcinomas, and adenoid basal carcinoma, but negative in all adenocarcinomas. Adenosquamous cell carcinoma and mixed neuroendocrine and squamous cell carcinoma were positive in squamous component, but not in adenocarcinoma and neuroendocrine carcinoma components. ME-180 cell line was positive, whereas HeLa cell line was negative. Endometrioid type of endometrial adenocarcinomas showed a positive staining in glandular (26.7%) and squamous component. CONCLUSIONS: Immunohistochemical staining for DeltaNp63 is a powerful marker for squamous differentiation and useful in exclusion of glandular and neuroendocrine differentiation in uterine cervical cancers, but not always in endometrial cancers.

Clinicopathological significance of maspin expression in breast cancer.

Maspin is a unique serine proteinase inhibitor that has tumor suppressor activity. It has been reported that maspin is expressed in normal human mammary epithelial cells and it is down-regulated during the progression of cancer. However, to date, there is very limited data on the clinical significance of maspin expression in human breast cancer. In this study, maspin expression was assessed immunohistochemically from 80 invasive ductal carcinoma (IDC) specimens of the breast. Also, maspin expression was compared with the clinicopathological factors (age, grade, tumor size and lymph node status), the expression of estrogen receptor (ER), progesterone receptor (PR) and p53, DNA ploidy and the overall survival in an attempt to assess its prognostic value. The maspin expression was positive in 25 IDC cases (31.3%). The maspin expression in IDC was significantly correlated with a higher histologic grade, a larger tumor size, a positive p53 status and shorter survival. There was an inverse association with maspin expression and the PR status. These findings suggest that maspin expression is not down-regulated with the progression of cancer and maspin expression may be associated with a poor prognosis. The immunohistochemical detection of maspin in breast cancers may be helpful for predicting an aggressive phenotype.