Prognostic Significance of Periostin and Mammalian Target of Rapamycin (mTOR) in Locally Advanced Esophageal Squamous Cell Carcinoma.

BACKGROUND Periostin and the mammalian target of rapamycin (mTOR) are involved in several cancers. This study aimed to evaluate the expression level of periostin and mTOR in locally advanced esophageal squamous cell carcinoma (ESCC) and to analyze their correlations with prognostic value. MATERIAL AND METHODS Expression levels of periostin and mTOR were examined by immunohistochemistry in locally advanced ESCC and corresponding adjacent normal tissue of 71 patients. The expression of periostin and mTOR were correlated with clinicopathologic characteristics by χ² test or Kruskal-Wallis analysis. The prognostic factors of periostin and mTOR on overall survival (OS) and disease-free survival (DFS) were assessed using Kaplan-Meier and Cox regression methods, respectively. RESULTS The high expression of periostin was significantly correlated to tumor stage (P=0.000), vascular invasion (P=0.027), differentiation (P=0.002), invasion depth (P=0.023), and lymph node metastasis (P=0.017). The high expression of mTOR was associated with tumor stage (P=0.001), lymphatic metastasis (P=0.014), and differentiation (P=0.036). Expression levels of periostin and mTOR was positively correlated (r=0.416, P=0.000). The OS and DFS in patients in the high-periostin group were significantly shorter than those in the low-periostin group, (both P<0.001). Similar results were found in mTOR analysis. Moreover, Cox regression analysis showed that the expressions of periostin and mTOR, along with tumor stage, were the independent factors affecting the survival time of ESCC patients. CONCLUSIONS Expressions of periostin and mTOR are related to multiple clinicopathologic features. High expression of periostin and mTOR were independent risk factors of ESCC patients, which might offer a potential target strategy for ESCC treatment in the future.

Hepatoprotective versus oncogenic functions of STAT3 in liver tumorigenesis.

Aberrantly hyperactivated STAT3 has been found in human liver cancers as an oncogene; however, STAT3 has also been shown to exert hepatoprotective effects during liver injury. The balancing act that STAT3 plays between hepatoprotection and liver tumorigenesis remains poorly defined. In this study, the diethylnitrosamine (DEN)-induced liver tumor model and the chronic carbon tetrachloride (CCl(4))-induced liver fibrosis model were both used to investigate the role of STAT3 in liver tumorigenesis. Hepatocyte-specific STAT3 knockout mice were resistant to liver tumorigenesis induced by a single DEN injection, whose tumorigenesis was associated with minimal chronic liver inflammation, injury, and fibrosis. In contrast, long-term CCl(4) treatment resulted in severe hepatic oxidative damage, inflammation, and fibrosis but rarely induced liver tumor formation in wild-type mice. Despite the oncogenic function of STAT3 in DEN-induced liver tumor, hepatocyte-specific STAT3 knockout mice were more susceptible to liver tumorigenesis after 16 weeks of CCl(4) injection, which was associated with higher levels of liver injury, inflammation, fibrosis, and oxidative DNA damage compared with wild-type mice. These findings suggest that the hepatoprotective feature of STAT3 prevents hepatic damage and fibrosis under the condition of persistent inflammatory stress, consequently suppressing injury-driven liver tumor initiation. Once liver tumor cells have developed, STAT3 likely acts as an oncogenic factor to promote tumor growth.

Coexpression of periostin and EGFR in patients with esophageal squamous cell carcinoma and their prognostic significance.

BACKGROUND: Both periostin (PN) and epidermal growth factor receptor (EGFR) can predict the prognosis of several carcinomas alone. However, coexpression of PN and EGFR in esophageal squamous cell carcinoma (ESCC) still remains unknown. We aimed to clarify their relationship with clinicopathological factors and prognostic significance of their coexpression in ESCC. PATIENTS AND METHODS: In this single-center retrospective study, immunohistochemistry was performed to evaluate the expression of PN and EGFR in ESCC and paracarcinomatous tissues of 83 patients. The quantitative expression levels of PN and EGFR were examined in two ESCC and tumor-adjacent tissues. The levels of PN and EGFR expression were correlated with clinicopathological parameters by the χ (2) or Kruskal-Wallis method. Spearman's rank correlation test was performed to determine the relationship between PN and EGFR expression levels. Kaplan-Meier and Cox regression analyses were used to detect the prognostic factors of disease-free survival (DFS) and overall survival (OS). RESULTS: The high expression of PN protein in ESCC tissues was significantly associated with tumor length (P=0.044), differentiation grade (P=0.003), venous invasion (P=0.010), invasion depth (P=0.007), lymphatic metastasis (P=0.000), and tumor stage (P=0.000). The high expression of EGFR protein in ESCC tissues was only significantly related to lymphatic metastasis (P=0.000), invasion depth (P=0.022), and tumor stage (P=0.000). Kaplan-Meier analysis showed that high expression of PN was closely correlated to reduced OS (P=0.000) and DFS (P=0.000), which was consistent with EGFR expression. Cox regression analysis identified PN and EGFR as independent poor prognostic factors of OS and DFS in the ESCC patients (P<0.05). Moreover, the risk of death for the ESCC patients with low expression of two biomarkers and high expression of single biomarker was 0.243 times (P=0.000) and 0.503 times (P=0.030), respectively, than that for patients with high expression of two biomarkers. CONCLUSION: PN and EGFR are related to miscellaneous clinicopathologic characteristics. Coexpression of PN and EGFR is more closely to be of predictive value on ESCC development and progression, which may offer a novel and potential target strategy for ESCC treatment in the future.

Neuroendocrine differentiation in prostate cancer.

As any organ in the body human prostate is composed of many different types of cells as well as extracellular components. During prostate development, reciprocal cellular interactions between stromal cells and prostate epithelial cells ultimately lead to the development of a mature prostate. Normal prostate is composed of repeating cellular units that contain stromal and epithelial compartments. The epithelial compartment contains luminal epithelial cells, basal cells and a minor component of neuroendocrine cells whose function may be to regulate the growth, differentiation and secretory function of the prostate gland. Neuroendocrine cells are also evident in prostate cancer and numerous studies showed that its number increases in high grade and high stage tumors, particularly in hormonally treated and hormone-refractory (androgen-independent) prostate cancer. Although androgen withdrawal reduces the secretion of the andromedins from the prostate stromal cells that are critical for the survival for prostate epithelial cells, there is clear evidence that androgen receptor is also required for the tumorigenesis of human prostate cancer, and therefore androgen deprivation therapy likely works through inhibition of androgen receptor in the prostate epithelium. Because neuroendocrine cells lack androgen receptor and are likely androgen-independent, it is conceivable that hormonal therapy for advanced/metastatic prostate cancer, which consists of inhibiting androgen production and/or blocking androgen receptor function, will not eliminate neuroendocrine cancer cells. Instead, these cells may be enriched after the therapy and they may establish paracrine networks to stimulate androgen-independent proliferation of prostate cancer, leading to tumor recurrence. In this article, we will review the known functions of the neuroendocrine cells in prostate cancer, including stimulation of cancer proliferation and invasion, apoptosis resistance and angiogenesis as well as molecular pathways involved in neuroendocrine differentiation.