Mortality Risk factors and SOX2 and mTOR expression in Patients with Esophageal Cancer.

Causes of mortality in EC patients are not confined to cancer-specific mortality but include various protein expressions of SOX2 and mTOR in Esophageal Cancer patients and their correlation with the clinical stage. Data about the risk factors and involvement of cancer-specific protein are still lacking. This study aimed to define the risk factors and association of SOX2 and mTOR expression in mortality in patients with EC. We conducted a retrospective cohort study to assess the risk factors for cancer-specific mortality and cardiovascular mortality in patients with esophageal cancer (EC). The expression rates of SOX2, as well as MTO, were checked in patients. The multivariate analysis revealed a high-risk EC mortality with age ≥ 65 years, black race, grade, stage, and sequence of treatment; radiation after surgery; radiation before and after surgery; Surgery both before and after radiation. While the cardiovascular mortality increased with age ≥ 65 years, adenocarcinoma type, grade, stage, and sequence of treatment. The expression rates of SOX2, as well as mTOR, were 75.5 percent and 86.8 percent in Esophageal Cancer, while were 10.7 percent and 7.5 percent in osteochondroma, respectively, which was statistically significant (P<0.05). Risk factors for cancer-specific mortality and cardiovascular mortality in EC patients include older age at diagnosis, male sex, non-married status, grade III of the tumor, the regional or distant spread of the tumor, no cancer-directed therapy. The expression levels of SOX2, mTOR, and the total survival time were related to the different stages. It shows an upward trend for the expression levels of mTOR and SOX2 in Esophageal Cancer tissues. The expression levels of SOX2 and mTOR are related to the clinical stage, metastasis, and prognosis.

PITX2: a promising predictive biomarker of patients' prognosis and chemoradioresistance in esophageal squamous cell carcinoma.

The paired-like homeodomain transcription factor 2 (PITX2), a downstream effector of wnt/ß-catenin signaling, is well known to play critical role during normal embryonic development. However, the possible involvement of PITX2 in human tumorigenesis remains unclear. In this study, we extend its function in human esophageal squamous cell carcinoma (ESCC). The real-time PCR, Western blotting and immunohistochemistry (IHC) methods were applied to examine expression pattern of PITX2 in two different cohorts of ESCC cases treated with definitive chemoradiotherapy (CRT). Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff point for PITX2 high expression in the training cohort. The ROC-derived cutoff point was then subjected to analyze the association of PITX2 expression with patients' survival and clinical characteristics in training and validation cohort, respectively. The expression level of PITX2 was significantly higher in ESCCs than that in normal esophageal mucosa. There was a positive correlation between PITX2 expression and clinical aggressiveness of ESCC. Importantly, high expression of PITX2 was observed more frequently in CRT resistant group than that in CRT effective group (p < 0.05). Furthermore, high expression of PITX2 was associated with poor disease-specific survival (p < 0.05) in ESCC. Then, the MTS, clonogenic survival fraction and cell apoptosis experiments showed that knockdown of PITX2 substantially increased ESCC cells sensitivity to ionizing radiation (IR) or cisplatin in vitro. Thus, the expression of PITX2, as detected by IHC, may be a useful tool for predicting CRT resistance and serves as an independent molecular marker for poor prognosis of ESCC patients treated with definite CRT.

Mice lacking myotubularin-related protein 14 show accelerated high-fat diet-induced lipid accumulation and inflammation.

The phosphoinositide phosphatase, myotubularin-related protein 14 (MTMR14), has been reported to play an important role in the regulation of muscle performance, autophagy, and aging in mice. We previously showed that MTMR14-knockout (KO) mice gain weight earlier than their wild-type (WT) littermates even on a normal chow diet (NCD), suggesting that this gene might also be involved in regulating metabolism. In the present study, we evaluated the effect of MTMR14 deficiency on high-fat diet (HFD)-induced obesity, lipid accumulation, metabolic disorders, and inflammation in WT and MTMR14-KO mice fed with NCD or HFD. To this end, MTMR14-KO mice fed with HFD showed significantly increased body weight, blood glucose levels, serum triglyceride (TG) levels, and total cholesterol (TC) levels as compared to their age-matched WT control. Additionally, lipid accumulation also increased in the KO mice. Simultaneously, the expression of metabolism-associated genes (Glut4, adiponectin, and leptin) was different in the liver, muscle, and fatty tissue of MTMR14-KO mice fed with HFD. More importantly, the expression of several inflammation-associated genes (TNF-α, IL-6, IL-1ß, and MCP-1) dramatically increased in the liver, muscle, and fatty tissue of MTMR14-KO mice relative to control. Taken together, these results suggest that MTMR14 deficiency accelerates HFD-induced metabolic dysfunction and inflammation. Furthermore, the results showed that exacerbated metabolic dysfunction and inflammation may be regulated via the PI3K/Akt and ERK signaling pathways.