ABSTRACT
BACKGROUND: Phospholipid phosphatase 4 (PPAPDC1A or PLPP4) has been demonstrated to be involved in the malignant process of many cancers. The purpose of this study was to investigate the clinical significance and biological roles of PLPP4 in lung carcinoma. METHODS: PLPP4 expression was examined in 8 paired lung carcinoma tissues by real-time PCR and in 265 lung carcinoma tissues by immunohistochemistry (IHC). Statistical analysis was performed to evaluate the clinical correlation between PLPP4 expression and clinicopathological features and survival in lung carcinoma patients. In vitro and in vivo assays were performed to assess the biological roles of PLPP4 in lung carcinoma. Fluorescence-activated cell sorting, Western blotting and luciferase assays were used to identify the underlying pathway through which PLPP4 silencing mediates biological roles in lung carcinoma. RESULTS: PLPP4 is differentially elevated in lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SQC) tissues. Statistical analysis demonstrated that high expression of PLPP4 significantly and positively correlated with clinicopathological features, including pathological grade, T category and stage, and poor overall and progression-free survival in lung carcinoma patients. Silencing PLPP4 inhibits proliferation and cell cycle progression in vitro and tumorigenesis in vivo in lung carcinoma cells. Our results further reveal that PLPP4 silencing inhibits Ca2+-permeable cationic channel, suggesting that downregulation of PLPP4 inhibits proliferation and tumorigenesis in lung carcinoma cells via reducing the influx of intracellular Ca2+. CONCLUSION: Our results indicate that PLPP4 may hold promise as a novel marker for the diagnosis of lung carcinoma and as a potential therapeutic target to facilitate the development of novel treatment for lung carcinoma.
Subject(s)
Calcium Channels/metabolism , Carcinogenesis/metabolism , Lung Neoplasms/chemistry , Lung Neoplasms/metabolism , Phosphatidate Phosphatase/metabolism , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Gene Silencing , Humans , Kaplan-Meier Estimate , Lung/chemistry , Lung Neoplasms/mortality , Phosphatidate Phosphatase/genetics , PrognosisABSTRACT
OBJECTIVE: To study the expression of ER mRNA, presenilin 2 (PS2) and their relationship and clinicopathological significance in the pancreatic carcinoma. METHODS: The assay of ER mRNA was detected by in situ hybridization technique and the expression of PS2 was completed by immunohistochemical method of avidin-biotin complex in the 10% neutral formalin-fixed and routinely paraffin-embedded sections of specimen with pancreatic carcinoma. RESULTS: The positive rate and the score of PS2 were 45.7% and 1.82 +/- 1.34, also those of ER mRNA were 51.4% and 2.08 +/- 1.46 in 35 patients with pancreatic carcinoma. The highly positive correlations were found among the positive rate and the score of ER mRNA and PS2. The positive rate and the score were significantly higher in the cases of well-differentiated adenocarcinoma without metastasis than those in the ones of middle- or poorly-differentiated adenocarcinoma with metastasis. CONCLUSION: The expression of ER mRNA or PS2 might reflect the biological behaviors and hormone-dependent status of pancreatic carcinoma. The assay of ER mRNA and meanwhile the detection of PS2 might have important clinical values for better understanding sex-hormone dependence and raising the therapeutic effect of clinical endocrine therapy of the pancreatic carcinoma.