Combined effect of silica dust exposure and cigarette smoking on total and cause-specific mortality in iron miners: a cohort study.

BACKGROUND: Both cigarette smoking and long-term exposure to crystalline silica dust were reported to be associated with increased mortality. However, the combined effect of both factors has not been well evaluated. METHODS: We investigated a retro-prospective cohort of 7,665 workers from one Chinese iron mine with a median follow-up of 42.8 years. Cumulative silica exposure was estimated for each worker by linking work histories with a job-exposure matrix. Cigarette smoking information was collected through face-to-face questionnaires. Hazard ratios (HRs) for total and cause-specific mortality due to silica exposure and smoking were estimated using Cox proportional hazards models. RESULTS: A total of 2,814 deaths occurred during 315,772.9 person-years of follow-up. Significantly elevated mortality from all causes, cardiovascular disease, non-malignant respiratory disease and lung cancer was observed among silica-exposed workers, while elevated mortality from non-malignant respiratory disease and lung cancer was observed among smokers. Combined exposure to silica dust and cigarette smoking elevated the proportion of mortality and accounted for 21.2, 76.0, 35.7 and 81.4% of all causes, non-malignant respiratory disease, cardiovascular disease, and lung cancer, respectively. Significant additive joint effects of silica exposure and cigarette smoking on mortality from lung cancer (HR 1.893, 95% CI 0.628 to 3.441) and pneumoconiosis (6.457, 0.725 to 39.114), together with a significant multiplicative joint effect from all causes (1.002, 1.000 to 1.004) were observed. CONCLUSIONS: The present findings indicated that silica exposure in combination with cigarette smoking accounted for a fraction of extra deaths in our cohort. Our research showed the urgent need for smoking cessation and silica control among iron miners.

[Risk analysis and assessment of occupational hazard fromindiumand its compounds in manufacture of liquid crystal display panel].

OBJECTIVE: To understand the exposed positions and levels of indium and its compounds in manufacture of liquid crystal displays, and to evaluate the degree of occupational hazard from indium and its compounds. METHODS: On-site investigation of occupational health, occupational hazard monitoring, and occupational health examination were used to evaluate the degree of occupational hazard from indium and its compounds in three manufacturers of liquid crystal display panel in Shenzhen, Guangdong, China. RESULTS: The time-weighted average (TWA) and short-term exposure limit (STEL) concentrations of indium and its compounds to which sputtering machine operating positions were exposed were less than 0.002~0.004 mg/m³ and 0.006~0.007 mg/m³, respectively, both of which complied with the National Hygienic Standard (PC-TWA = 0.1 mg/m³; PC-STEL = 0.3 mg/m³); the TWA and STEL concentrations of indium and its compounds to which grinding positions were exposed were 0.114~2.98 mg/m³ and 0.31~10.02 mg/m³, respectively, both of which exceeded the National Hygienic Standard with the highest concentration 33-fold higher than the standard. No significant health damages were found in exposed workers according to the results of occupational health examination. CONCLUSION: The grinding positions are the key to the control of occupational hazard from indium and its compounds in manufacture of liquid crystal display panel. The workers should be equipped with the anti-particulate full-face respirator, which is an effective way to prevent occupational hazard from indium and its compounds.

Association of lymphocyte count and serum albumin concentration with telomere length in Chinese sanitation workers.

OBJECTIVE: This study aimed to examine the association between inflammation-related indicators (IRIs) and telomere length (TL) in Chinese sanitation workers. METHODS: This study adopted a case-control design, conducted from January to December 2022 in Shenzhen, a city in eastern China. A total of 80 sanitation workers, as well as 80 matched controls, were randomly recruited from the Luohu district of Shenzhen city in China. Their blood samples were collected and analyzed for the IRIs and TL in the Medical Laboratory of Shenzhen Prevention and Treatment Center for Occupational Diseases. The relationship between IRIs and TL was analyzed using multivariate linear regression, and their dose-response relationship was explored using restricted cubic spline analysis. RESULTS: The systemic inflammatory index (SII), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) were significantly elevated in the sanitation workers in comparison to the controls. Moreover, the lymphocyte count (LYM), serum albumin concentration (ALB), and TL were found to be lower in the sanitation workers compared to the controls (P < 0.05). After adjusting for potential confounding variables, LYM was negatively correlated with TL in the sanitation workers (ß = -0.31, 95% CI: -0.57, -0.05), whereas no correlation was observed in the controls. Furthermore, ALB demonstrated a non-linear relationship with TL in sanitation workers. CONCLUSION: We found higher novel inflammatory markers (SII, PLR, and NLR) in the sanitation workers, and identified a correlation between LYM and ALB with shortened TL in them, providing new evidence for the effect of elevated inflammation on accelerated aging in Chinese sanitation workers.

Long-term exposure to silica dust and risk of total and cause-specific mortality in Chinese workers: a cohort study.

BACKGROUND: Human exposure to silica dust is very common in both working and living environments. However, the potential long-term health effects have not been well established across different exposure situations. METHODS AND FINDINGS: We studied 74,040 workers who worked at 29 metal mines and pottery factories in China for 1 y or more between January 1, 1960, and December 31, 1974, with follow-up until December 31, 2003 (median follow-up of 33 y). We estimated the cumulative silica dust exposure (CDE) for each worker by linking work history to a job-exposure matrix. We calculated standardized mortality ratios for underlying causes of death based on Chinese national mortality rates. Hazard ratios (HRs) for selected causes of death associated with CDE were estimated using the Cox proportional hazards model. The population attributable risks were estimated based on the prevalence of workers with silica dust exposure and HRs. The number of deaths attributable to silica dust exposure among Chinese workers was then calculated using the population attributable risk and the national mortality rate. We observed 19,516 deaths during 2,306,428 person-years of follow-up. Mortality from all causes was higher among workers exposed to silica dust than among non-exposed workers (993 versus 551 per 100,000 person-years). We observed significant positive exposure-response relationships between CDE (measured in milligrams/cubic meter-years, i.e., the sum of silica dust concentrations multiplied by the years of silica exposure) and mortality from all causes (HR 1.026, 95% confidence interval 1.023-1.029), respiratory diseases (1.069, 1.064-1.074), respiratory tuberculosis (1.065, 1.059-1.071), and cardiovascular disease (1.031, 1.025-1.036). Significantly elevated standardized mortality ratios were observed for all causes (1.06, 95% confidence interval 1.01-1.11), ischemic heart disease (1.65, 1.35-1.99), and pneumoconiosis (11.01, 7.67-14.95) among workers exposed to respirable silica concentrations equal to or lower than 0.1 mg/m(3). After adjustment for potential confounders, including smoking, silica dust exposure accounted for 15.2% of all deaths in this study. We estimated that 4.2% of deaths (231,104 cases) among Chinese workers were attributable to silica dust exposure. The limitations of this study included a lack of data on dietary patterns and leisure time physical activity, possible underestimation of silica dust exposure for individuals who worked at the mines/factories before 1950, and a small number of deaths (4.3%) where the cause of death was based on oral reports from relatives. CONCLUSIONS: Long-term silica dust exposure was associated with substantially increased mortality among Chinese workers. The increased risk was observed not only for deaths due to respiratory diseases and lung cancer, but also for deaths due to cardiovascular disease. Please see later in the article for the Editors' Summary.

[The study of the characteristics and influencing factors of pneumoconiosis among workers exposed to dusts in an iron mine].

OBJECTIVE: To analyze the prevalence characteristics and influence factors of pneumoconiosis of workers exposed to dusts in an iron mine, to provide the base of preventive measures for pneumoconiosis of iron mine. METHODS: The subjects of cohort study were all workers exposed to dusts for at least one year registered in an iron mine during 1960 to 1974, and followed-up to the end in 2003. The cases with pneumoconiosis were diagnosed by the local diagnosis group of pneumoconiosis, according to the national diagnostic criteria of pneumoconiosis. The risk factors were analyzed with Cox risk model. RESULTS: A total of 3647 miners were included in the cohort study and were followed up by 132 574.4 person years. There were 316 cases with pneumoconiosis, and the incidence of pneumoconiosis for a year was 0.24 per thousand. There were 274 cases (86.7%) with pneumoconiosis in workers exposed to dusts before 1960, the incidence of pneumoconiosis for a year was 0.40 per thousand, which was significantly higher than that (0.07 per thousand) of workers exposed to dusts after 1960. The average latency of pneumoconiosis was 26.0 +/- 7.3 years. The average durations of upgrade from stage 0(+) to I , I to II and II to III were 5.3 +/- 3.2, 6.6 +/- 5.2 and 11.3 +/- 5.0 years, respectively. However, 164 cases with pneumoconiosis were diagnosed after ceasing exposure to dusts for mean 8.3 years. The risk of pneumoconiosis in iron miners increased with exposure doses, and there was an obvious dose-effect relationship. The average cumulative exposure dose of cases with pneumoconiosis was 173.7 +/- 91.6 mg/m3 x y, which was significantly higher than that (112.1 +/- 64.8 mg/m3 x y) of workers without pneumoconiosis. Also the tuberculosis (HR = 5.9, P < 0.001) and smoking (HR = 1.7, P < 0.01) were the main risk factors. CONCLUSION: There was an obvious dose-effect relationship between the cumulative exposure dose and pneumoconiosis incidence. Tuberculosis and smoking were the main risk factors influencing the pneumoconiosis incidence.

[The analysis of adverse health effects of occupational hazards factors in one solid waste landfill].

OBJECTIVE: To determine occupational hazards in work sites of a large solid waste landfill and analyze their adverse health effects. METHOD: The national standardized detection methods were used to determine dust concentration, harmful gas and physical factors in worksites. Routine physical examination, pulmonary function, hearing tests and nervous system test were performed in workers for 2 consecutive years. Urine lead, cadmium and mercury contents were detected. The comet assay was use to measure DNA damage in peripheral blood lymphocytes among workers. RESULT: The main occupational hazard factors in this solid landfill are dust, harmful gas, high temperature and noise. The oxides, carbon monoxide, and noise and high temperatures in summer at some work sites exceeded the national occupational exposure limits. The prevalence of respiratory inflammation and rate of pulmonary function decrease among front-line workers and on-site technical managers are 21.2% and 11.5%, which are significantly higher than those among administrative staff (7.1% and 0) (P < 0.05). Nervous system abnormalities rate of front-line workers and on-site technical managers was 50.0%, which is significantly higher than that (26.7%) of administrative staff (P < 0.05). Because of long-term exposure to high intensity noice, hearing loss rate of bulldozer drivers was 10.3%. In addition, about 75% of workers with DNA damage in peripheral blood lymphocyte are front-line workers. CONCLUSION: Adverse health effects from occupational hazards were observed among workers in this solid waste landfill.

[Experimental research on biological responses of productive dusts from pottery factories and tungsten mines].

OBJECTIVE: To assess biological response and health adverse effects of industrial dusts from pottery factories and tungsten mines on alveolar macrophages (AM) in vitro. METHODS: AM acquired from bronchoalveolar lavage of guinea pigs were used as the target cells. AM were then co-cultured with respirable dust particles (15, 30, 60 and 120 µg/106) from pottery factories and tungsten mines. LDH activity, cell viability, the release of ROS and TNF-α were determined to assess the biological responses of the dusts. China Standard Quartz was used as control. RESULTS: Dose- response relationships between the dust concentrations and the enhancement of LDH activity, the release of ROS and TNF-α were found in both dusts from pottery factories and tungsten mines. The cell viability decreased when the dusts' concentrations increased. Differences of biological response were observed in the dust particles from different mines or factories. Compared with the pottery dusts, higher LDH activity and the release of TNF-α induced by tungsten dust were observed. In the 120 µg/106 group, the TNF-α induced by tungsten dust, pottery dusts and China Standard Quartz was (5.2 +/- 2.0) ng/ml, (3.3 +/- 1.6) ng/ml and (2.8 +/- 0.5) ng/ml respectively. However, the impact on the cell viability induced by pottery dust was higher than that by tungsten mine. CONCLUSION: Industrial dusts from various sources could induce different biological effects. The results of the biological effects of dusts in laboratory tests may be of potential use to provide base data for their adverse effects evaluation.

Influence of exercise at high temperature on blood biochemical indexes and HSP72 expression in adult males.

The influence of exercise at high temperature on adult males' routine blood indexes and biochemical indexes and the expression of HSP72 in peripheral blood lymphocytes (PBLs) was studied in order to provide theoretical ground for health supervision of adults receiving exercise at high temperature. 180 adult males were selected and divided into exercise group and control group, in which the exercise group was subdivided into subgroup 1 and subgroup 2 receiving exercise at high temperature in the afternoon and in the morning, respectively. Peripheral venous blood was phlebotomized before and after the exercise to examine routine blood indexes and blood biochemical indexes. The expression levels of HSP72 in PBLs were detected by flow cytometry. The results showed that the routine blood indexes and biochemical indexes in each group were within the range of normal values of male adults. There was no significant difference between each exercise group and control group in indexes before exercise. After exercise, the expression levels of HSP72 in PBLs in exercise groups were higher than those before exercise, and HSP72 expression levels in subgroup 1 were obviously higher than those in subgroup 2 and control group. The contents of ALT, urea, Na+, Cl-, Ca2+ and K+ in subgroups 1 and 2 were lower than those in control group, but CK level was higher than in control group (P<0.05). The contents of Na+ and Cl- in subgroup 1 were relatively lower than those in subgroup 2 (P<0.05). It was concluded that while receiving exercise at high temperature, adult males' HSP72 levels in PBLs could be increased and the biochemical indexes changed. Attention should be paid to health supervision to avoid obvious body injuries at high temperature.

[Effect of humidity and temperature on filter and gravimetric measurement of ambient particulate matter in a balance room].

OBJECTIVE: To assess the effects of the alteration of humidity and (or) temperature on weight of filters without and with ambient particulate matter in a balance room. METHODS: The mass of blank dust sampling filters were weighed under (18 +/- 1) degrees C and (28 +/- 1) degrees C respectively, with the humidity varying from 35% relative humidity (RH) to 100% RH in a balance room. Then the blank filters were divided into two groups and were used to sample total dust and respirable dust. After sampling, the loaded filters were re-weighed under above conditions and the mass difference before and after the sampling were compared and analyzed. RESULTS: The vibration of the average mass of filters varied from 0.10 to 0.13 mg and from 0.06 to 0.09 mg under the temperatures of (18 +/- 1) degrees C and (28 +/- 1) degrees C respectively; When both the temperature and humidity changed, it varied from 0.12 to 0.16 mg. The deviation of average mass difference ranged from 0.07 to 0.10 mg and from 0.04 to 0.08 mg under the two temperatures mentioned above; When both the temperature and humidity changed, it varied from 0.09 to 0.14 mg. The average mass of blank filters and loaded filters were all positively correlated with the change of humidity (P < 0.01). No effects of humidity on the average mass difference of the loaded filters were observed. The average mass differences of loaded filters and blank filters under (18 +/- 1) degrees C were significantly higher than that under (28 +/- 1) degrees C (P < 0.01) when humidity was not changed. CONCLUSION: The alteration of humidity and (or) temperature in a balance room attributes to the deviation of the measurement of the mass of filters and thus affects the gravimetric measurements of ambient particulate matter.

Effects of the Interactions between Dust Exposure and Genetic Polymorphisms in Nalp3, Caspase-1, and IL-1ß on the Risk of Silicosis: A Case-Control Study.

OBJECTIVES: To evaluate the effects of the interactions between polymorphisms in Nalp3, caspase-1, and interleukin(IL)-1ß genes and occupational dust exposure on the risk of silicosis. METHODS: We conducted a population-based case-control study in a large iron mine in China. Between January 2006 and December 2009, we identified 179 patients with silicosis to evaluate as cases and 201 individuals without silicosis to evaluate as controls. We estimated cumulative dust exposure (CDE) for all subjects and we genotyped polymorphisms in Nalp3, caspase-1, and IL-1ß genes. We estimated odds ratios(ORs), 95% confidence intervals(95%CIs), and p-values using logistic regression models adjusted for selected confounders. RESULTS: After adjusting for age, smoking status, and CDE, subjects with the CT genotype of Ex4-849C>T in Nalp3 and the GA genotype of Ex2+37G>A in caspase-1 had increased risks of silicosis (adjusted ORs[95%CIs] = 2.40 [1.12-5.12] and 3.62 [1.63-8.02], respectively). Among subjects younger than 70 years old, those with the CC genotype of IVS8-7652A>C in Nalp3 had a lower risk of silicosis than those with other genotypes (adjusted OR[95%CI] = 0.24[0.06-0.88]). Among subjects aged 70 years and older, those with the CT genotype of Ex4-849C>T in Nalp3 and those with the GA genotype of Ex2+37G>A in caspase-1 had a higher risk of silicosis than those with other genotypes (adjusted ORs [95%CI] = 2.52[1.04-6.12] and 5.19[1.88-14.35], respectively). Among subjects with CDE greater than 120 mg/m3×year and among smokers, those with the GA genotype of Ex2+37G>A in caspase-1 had a higher risk of silicosis than those with other genotypes (adjusted ORs[95%CIs] = 26.37[3.35-207.39] and 3.47[1.40-8.64], respectively). CONCLUSIONS: Genetic polymorphisms in Nalp3 and caspase-1 may be associated with individual susceptibility to silicosis, especially when the polymorphisms interact with age, CDE, or smoking status.

Occupational Hearing Loss among Chinese Municipal Solid Waste Landfill Workers: A Cross-Sectional Study.

BACKGROUND: Occupational hearing loss is an increasingly prevalent occupational condition worldwide, and has been reported to occur in a wide range of workplaces; however, its prevalence among workers from municipal solid waste landfills (MSWLs) remains less clear. This study aimed to investigate the occupational hearing loss among Chinese MSWL workers. METHODS: A cross-sectional study of 247 workers from 4 Chinese MSWLs was conducted. Noise and total volatile organic compounds (TVOCs) levels at worksites were determined. We conducted hearing examinations to determine hearing thresholds. A worker was identified as having hearing loss if the mean threshold at 2000, 3000 and 4000 Hz in either ear was equal to or greater than 25 dB. Prevalence of occupational hearing loss was then evaluated. Using unconditional Logistic regression models, we estimated the odds ratios (ORs) of MSWL work associated with hearing loss. RESULTS: According to the job title for each worker, the study subjects were divided into 3 groups, including group 1 of 63 workers without MSWL occupational hazards exposure (control group), group 2 of 84 workers with a few or short-period MSWL occupational hazards exposure, and group 3 of 100 workers with continuous MSWL occupational hazards exposure. Both noise and TVOCs levels were significantly higher at worksites for group 3. Significantly poorer hearing thresholds at frequencies of 2000, 3000 and 4000 Hz were found in group 3, compared with that in group 1 and group 2. The overall prevalence rate of hearing loss was 23.5%, with the highest in group 3 (36.0%). The OR of MSWL work associated with hearing loss was 3.39 (95% confidence interval [CI]: 1.28-8.96). CONCLUSION: The results of this study suggest significantly higher prevalence of hearing loss among MSWL workers. Further studies are needed to explore possible exposure-response relationship between MSWL occupational hazards exposure and hearing loss.

The cell cycle regulator 14-3-3σ opposes and reverses cancer metabolic reprogramming.

Extensive reprogramming of cellular energy metabolism is a hallmark of cancer. Despite its importance, the molecular mechanism controlling this tumour metabolic shift remains not fully understood. Here we show that 14-3-3σ regulates cancer metabolic reprogramming and protects cells from tumorigenic transformation. 14-3-3σ opposes tumour-promoting metabolic programmes by enhancing c-Myc poly-ubiquitination and subsequent degradation. 14-3-3σ demonstrates the suppressive impact on cancer glycolysis, glutaminolysis, mitochondrial biogenesis and other major metabolic processes of tumours. Importantly, 14-3-3σ expression levels predict overall and recurrence-free survival rates, tumour glucose uptake and metabolic gene expression in breast cancer patients. Thus, these results highlight that 14-3-3σ is an important regulator of tumour metabolism, and loss of 14-3-3σ expression is critical for cancer metabolic reprogramming. We anticipate that pharmacologically elevating the function of 14-3-3σ in tumours could be a promising direction for targeted anticancer metabolism therapy development in future.

LRH1 as a driving factor in pancreatic cancer growth.

Liver receptor homolog 1 (LRH1), directs the development and differentiation of embryonic pancreas, and is overexpressed in pancreatic cancer (PC). We hypothesized that LRH1 promotes PC growth. Cell proliferation and tumorigenicity in nude mice were compared between empty vector-transfected (control) and stable LRH1-overexpressed PC cell lines. The subsequent tumor burden, vasculature development, and histologic features were evaluated. LRH1 overexpression enhanced the expression of downstream target genes (cyclin D1/E1) and stimulated cell proliferation in PC cell lines. LRH1 upregulated cyclin E1 truncated T1/T2 isoforms expression which may occur through ERα-calpain1 signaling. Compared with the control, LRH1 overexpressing stable cells generated tumors with increased weight, proliferation index and enhanced angiogenesis. Cyclin D1/E1 and calpain1 were overexpressed in human PC tumors compared to adjacent normal pancreas. These observations demonstrate that LRH1 promotes PC growth and angiogenesis, suggesting that LRH1 is a driving factor in tumorigenesis and may serve as a potential therapeutic target.

LRH1 promotes pancreatic cancer metastasis.

The transcriptional factor liver receptor homolog 1 (LRH1) regulates pancreatic development, and may participate in pancreatic oncogenesis through activation of growth factor signaling transduction cascades. We measured transcriptional activity of ß-catenin in response to LRH1 stimulation by a Topflash reporter assay. The pancreatic cancer (PC) phenotype was then characterized by cell migration, wound healing, invasion, and sphere formation in vitro, as well as tumor formation and distant metastatic spread in vivo. We compared results between vector control and LRH1-overexpressing stable PC cell lines. In addition, tumor burden, angiogenesis, histologic characteristics, and hepatic spread were assessed in orthotopic and experimental liver metastatic murine models. Expression of downstream LRH1 related genes was evaluated by Western blot and immunohistochemistry in PC cell lines and human tumor specimens. Specific inhibition of LRH1 expression and function was accomplished by shRNAs "knockdown" experiments. It was found that LRH1 enhanced transcriptional activity of ß-catenin and the expression of downstream target genes (c-Myc, MMP2/9), as well as promoted migration, wound healing, invasion, and sphere formation of PC cell lines. Specific inhibition of LRH1 by shRNAs reduced cell migration, invasion, sphere formation and expression of c-Myc and MMP2/9 target genes. Mice injected with LRH1 overexpressing stable PC cells developed tumors with increased size and exhibited striking hepatic metastatic spread. More important, LRH1 was overexpressed in PC tumors compared to adjacent normal pancreas. Our findings demonstrate that LRH1 overexpression is associated with increased PC growth and metastatic spread, indicating that LRH1-targeted therapy could inhibit tumor progression.

Polychlorinated dibenzo-p-dioxins and dibenzofurans and their association with cancer mortality among workers in one automobile foundry factory.

Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) have been reported as possible carcinogenic hazards to humans. However, epidemiological studies on their carcinogenic roles are limited. The current study was designed to determine the concentrations and characteristics of PCDD/Fs and evaluate their association with cancer mortality in exposed workers in one automobile foundry factory. PCDD/F levels in factory and surrounding environment were analyzed through air and settling dust sampling. The cancer mortalities among workers in this foundry factory were calculated using data from a cohort study. The results showed that the PCDD/F concentrations of air in workplace ranged 0.36-2.25 pg World Health Organization-Toxic Equivalent (WHO-TEQ) Nm(-3) (average 1.01 pg WHO-TEQ Nm(-3)), which were 1.16-7.26 times higher than those outside the factory. The PCDD/F concentrations of settling dust in the workplace ranged 3.34-18.64 pg WHO-TEQ g(-1) (average 8.25 pg WHO-TEQ g(-1)), which were lower than those just outside the factory (average 16.13 pg WHO-TEQ g(-1)). Furthermore, a cohort study of workers in this factory with average follow-up of 24.52 years showed that cancer was the leading cause of death, with significant elevated mortality (standardized mortality ratio (SMR)=1.70, 95% confidence interval (CI): 1.35-2.13) among workers, when compared with Chinese national mortality. The cancer mortality among front-line workers was increased significantly (adjusted relative risk (RR)=1.73, 95% CI: 1.14-2.60), particularly among melting and casting workers, when compared with that among assistant workers. Our results indicated that there was a dose-response relationship between PCDD/F exposure and cancer mortality among foundry workers.

Overexpression of protein phosphatase 4 correlates with poor prognosis in patients with stage II pancreatic ductal adenocarcinoma.

PURPOSE: Protein phosphatase 4 (PP4) has been reported to be overexpressed in breast and lung cancers. PP4 plays an important role in the regulation of centrosome maturation, DNA repair, NF-κB, and c-jun-NH(2)-kinase (JNK) signaling pathways. However, the expression and functions of PP4 in pancreatic cancer have not been studied. EXPERIMENTAL DESIGN: We examined the expression of PP4 catalytic subunit (PP4C) protein in 133 patients with stage II pancreatic ductal adenocarcinoma (PDAC) and their paired benign pancreatic samples (N = 113) by immunohistochemistry. To confirm the immunohistochemical results, we measured PP4C protein and mRNA levels by Western blotting and real-time reverse transcriptase PCR. Using univariate and multivariate analysis, we correlated PP4C expression with survival and other clinicopathologic features. RESULTS: PP4C was overexpressed in 75 of 133 (56.4%) stage II PDAC samples, which was significantly higher than the paired benign pancreatic tissue (15%, 17 of 113). PP4C mRNA expression levels were also higher in PDAC samples than the paired benign pancreatic tissue. Overexpression of PP4C in PDAC samples was associated with higher frequencies of distant metastasis (P = 0.02) and poor disease-free and overall survivals in patients with stage II PDAC (P = 0.006 and 0.02) independent of tumor size, margin status, and lymph node status (stage). CONCLUSIONS: Our study showed that PP4C is overexpressed in PDAC. Overexpression of PP4C in PDAC samples is associated with poor prognosis in patients with stage II PDAC. Therefore, targeting PP4 signaling pathway may represent a new approach for the treatment of PDAC. IMPACT: Our study showed that PP4C is an independent prognostic factor in patients with stage II PDAC.