Role and mechanism of FLNa and UCP2 in the development of cervical cancer.

Recent studies have reported that filamin A (FLNa) and uncoupling protein 2 (UCP2) are highly expressed in various types of cancer, but little is currently known about their roles in cervical cancer (CC). In the present study, immunohistochemical staining of paraffin sections of cervical tissues was performed in order to compare the differential expression of FLNa, UCP2, p16 and Ki67 between CC and high­grade intraepithelial neoplasia (HSIL). UCP2 and FLNa were knocked down in CC cell lines to investigate the effects on cell proliferation, cell cycle arrest, apoptosis, migration and invasion. In addition, the present study investigated the expression of cell­associated proteins [extracellular signal­regulated kinase (ERK), phosphorylated (p) ERK, protein kinase B (AKT), p­AKT and B­cell lymphoma­2 (Bcl­2)] and the mRNA levels of cellular proteins such as Ras, matrix metalloproteinase (MMP)­2 and MMP­9. FLNa and UCP2 expression levels were significantly higher in CC tissues than in HSIL tissues, with no significant differential expression of p16 or Ki67. UCP2 expression was significantly different in patients with clinical stage II or higher or lymph node metastasis compared with in other patients with cervical cancer. FLNa or UCP2 knockdown slowed or decreased SiHa and HeLa cell proliferation, migration and invasion, with no significant change in apoptosis, and downregulated the protein levels of p­ERK1/2, and the mRNA levels of Ras, MMP­2 and MMP­9. UCP2 knockdown arrested the cell cycle at the G2 phase in SiHa and HeLa cells, while FLNa knockdown arrested the cell cycle at the G2 phase in HeLa cells. The results of the present study revealed that FLNa and UCP2 play roles in the development and progression of CC via the Ras/MAPK/ERK signalling pathway. FLNa and UCP2 are superior to p16 and Ki67 for early prediction of CC, indicating that FLNa and UCP2 may be used for the early diagnosis of CC. UCP2 may be used to predict the prognosis of CC.

Esophageal Histological Precursor Lesions and Subsequent 8.5-Year Cancer Risk in a Population-Based Prospective Study in China.

INTRODUCTION: Data on the associations between esophageal histological lesions and risk of esophageal squamous cell carcinoma (ESCC) in general populations are limited. We aimed to investigate these associations in a large Chinese general population to inform future Chinese ESCC screening guidelines. METHODS: We performed endoscopic screening of 21,111 participants aged 40-69 years from 3 high-risk areas of China in 2005-2009, and followed the cohort through 2016. Cumulative incidence and mortality rates of ESCC were calculated by baseline histological diagnosis, and hazard ratios of ESCC, overall and by age and sex, were assessed using the Cox proportional hazards models. RESULTS: We identified 143 new ESCC cases (0.68%) and 62 ESCC deaths (0.29%) during a median follow-up of 8.5 years. Increasing grades of squamous dysplasia were associated with the increasing risk of ESCC incidence and mortality. The cumulative ESCC incidence rates for severe dysplasia/carcinoma in situ, moderate dysplasia (MD), and mild dysplasia were 15.5%, 4.5%, and 1.4%, respectively. Older individuals (50-69 years) had 3.1 times higher ESCC incidence than younger individuals (40-49 years), and men had 2.4 times higher ESCC incidence than women. DISCUSSION: This study confirmed that increasing grades of squamous dysplasia are associated with increasing risk of ESCC and that severe dysplasia and carcinoma in situ require clinical treatment. This study suggests that in high-risk areas of China, patients with endoscopically worrisome MD should also receive therapy, the first screening can be postponed to 50 years, and endoscopic surveillance intervals for unremarkable MD and mild dysplasia can be lengthened to 3 and 5 years, respectively.

Long-term effectiveness of one-time endoscopic screening for esophageal cancer: A community-based study in rural China.

BACKGROUND: Evidence is required to quantify the population-level effects of endoscopic screening for esophageal squamous cell carcinoma (ESCC). The objective of this study was to evaluate the long-term effectiveness of 1-time endoscopic ESCC screening in a Chinese rural population. METHODS: This community-based cohort study was based on an existing esophageal cancer screening program in Feicheng City, China. The screening group consisted of all permanent residents aged 40 to 69 years in 17 villages who were screened during 2006 through 2009, and the control group consisted of residents in another 43 villages who were not yet covered by the screening program. Residents in the remaining 511 villages were defined as the total population control. The cumulative incidence and mortality of ESCC and the observed and expected numbers of ESCC cases and deaths during the follow-up period (2010-2018) were calculated and compared. RESULTS: After a 9-year follow-up, the screening group (n = 8460) revealed reductions of 20% (relative risk, 0.80; 95% CI, 0.66-0.97) and 32% (relative risk, 0.68; 95% CI, 0.52-0.89) in ESCC cumulative incidence and mortality, respectively, compared with the control group (n = 20,468). Endoscopic screening prevented 0.41% of the population (attributable risk, 0.41%; 95% CI, 0.07%-0.75%) from ESCC occurrence and 0.38% (attributable risk, 0.38%; 95% CI, 0.14%-0.62%) from ESCC-related death. In the screening group, reductions of 43% (standardized incidence ratio, 0.57; 95% CI, 0.48-0.67) and 45% (standardized mortality ratio, 0.55; 95% CI, 0.44-0.69) were found in the observed cumulative cases and deaths, respectively, compared with the expected cases and deaths. CONCLUSIONS: One-time endoscopic screening was associated with a significant and consistent reduction in ESCC incidence and mortality among individuals aged 40 to 69 years in high-risk areas.

Environmental factors, seven GWAS-identified susceptibility loci, and risk of gastric cancer and its precursors in a Chinese population.

Gene-environment interactions may increase gastric cancer (GC) risk. Seven susceptibility loci identified by genome-wide association studies (GWASs) suggest that genetic factors play a role in gastric carcinogenesis. Meanwhile, Helicobacter pylori (H. pylori) infection, smoking, and alcohol drinking are also important environmental factors for gastric cancer. However, studies to explore the role of gene-environment interactions in gastric carcinogenesis, and particularly the relationship between the seven susceptibility loci and their potential interactions with H. pylori infection, smoking, and alcohol drinking in risk of GC, and severe intestinal metaplasia (IM)/dysplasia, have been inconclusive. A total of 1273 subjects in a Chinese population were recruited, and genotyping was carried out using the competitive allele-specific PCR (KASP) method. Unconditional logistic regression was applied to model the associations between genetic polymorphisms and the disease risk. Effect modifications by H. pylori infection, smoking and alcohol drinking were evaluated. PSCA rs2294008/rs2976392 showed a significant, multiplicative interaction with H. pylori infection in risk of GC. Meanwhile, PRKAA1 rs13361707 had an additive interaction with H. pylori infection. SLC52A3 rs13042395 showed an interaction with alcohol drinking in risk of GC. Moreover, three SNPs, MUC1 rs4072037, ZBTB20 rs9841504 and PRKAA1 rs13361707, were associated with precancerous gastric lesions (severe IM/dysplasia). Our data suggest that genetic predisposition factors identified by GWAS may interact with environmental risk factors, Particularly for H. pylori infection and alcohol consumption, to increase the risk of GC.

[Distribution of esophageal squamous cell cancer and precursor lesions in high-risk areas, Linzhou in Henan province and Feicheng in Shandong province of China, 2005-2009].

OBJECTIVE: To understand the distribution of esophageal squamous cell cancer and precursor lesions in high-risk areas of China, and to provide evidence for determining the reference ranges of detection rates in high-risk areas. METHODS: Endoscopy with Lugol's iodine staining was performed on 15 709 local residents aged 40 to 69 years old in Linzhou of Henan province and Feicheng of Shandong province from 2005-2009. 35 cases without accurate pathology diagnosis and 11 cases with vital disease before screening were excluded. 15 663 subjects were enrolled in this study. Compliance was calculated by the percentage of the people who had endoscopic screening among the target population. Chi-square test and trend chi-square test were used to compare the distribution differences in age, gender and areas of esophageal squamous cell cancer and precancer. 95% CI of the detection rates was then employed to represent the reference ranges of esophageal squamous cell cancer and precursor lesions. RESULTS: The compliance rate of screening endoscopy of this study was 49.36% (15 709/31 826) of all, and female's compliance (54.05%, 8 447/15 628) was much higher than that of male (44.83%, 7 262/16 198) (χ(2) = 88.14, P < 0.001). The detection rates of basal cell hyperplasia, low grade intraepithelial neoplasia, high grade intraepithelial neoplasia and esophageal squamous cell cancer of males were 4.17% (302/7 246), 17.22% (1 248/7 246), 1.67% (121/7 246), 0.83% (60/7 246), and were higher than that of females (3.45% (290/8 417), 14.82% (1 247/8 417), 1.41% (119/8 417), 0.48% (40/8 417), respectively). Except for high-grade intraepithelial neoplasia, the detection rates of male were higher than that of female (P values were 0.018, < 0.001, 0.960, 0.006). The detection rates of all grades of precursor lesions increased with age rising (all P values < 0.001), among which the detection rates of the mentioned four lesions for 40-44 years old were 2.69% (94/3 500), 8.11% (284/3 500), 0.40% (14/3 500), 0.14% (5/3 500), and that of 65-69 years old were 5.46% (46/843), 23.25% (196/843), 3.68% (31/843), 2.14% (18/843). The proportion of esophageal precursor lesion of Linzhou were higher than that of Feicheng observably except for esophageal squamous cell cancer (P values were < 0.001, < 0.001, < 0.001, 0.437). The detection rates of the four lesions of Linzhou and Feicheng were 4.90% (504/10 287), 17.37% (1 787/10 287), 1.79% (184/1 0287), 0.60% (62/10 287) and 1.64% (88/5 376), 13.17% (708/5 376), 1.04% (56/5 376), 0.71% (38/5 376). The 95% CI of detection rates of various lesions were, 3.78% (3.48%-4.08%) for basal cell hyperplasia, 15.93% (15.37%-16.50%) for low-grade intraepithelial neoplasia, 12.31% (11.79%-12.82%) for mild dysplasia and 3.62% (3.33%-3.91%) for moderate hyperplasia, 1.53% (1.34%-1.72%) for high-grade intraepithelial neoplasia and 0.64% (0.51%-0.76%) for esophageal squamous cell cancer, respectively. CONCLUSION: Up to 21.88% residents that were asymptomatic were suffered from esophageal squamous cancer or precursor lesions in high-risk areas in China. The distribution of esophageal squamous cell cancer and precursor lesions was closely related to the gender and the age, which suggested that males were supposed to be paid more attention to.

Population-based study of DNA image cytometry as screening method for esophageal cancer.

AIM: To explore the DNA image cytometry (DNA-ICM) technique as a primary screening method for esophageal squamous precancerous lesions. METHODS: This study was designed as a population-based screening study. A total of 582 local residents aged 40 years-69 years were recruited from Linzhou in Henan and Feicheng in Shandong. However, only 452 subjects had results of liquid-based cytology, DNA-ICM and pathology. The sensitivity and specificity of DNA-ICM were calculated and compared with liquid-based cytology in moderate dysplasia or worse. RESULTS: Sensitivities of DNA-ICM ranging from at least 1 to 4 aneuploid cells were 90.91%, 86.36%, 79.55% and 77.27%, respectively, which were better than that of liquid-based cytology (75%). Specificities of DNA-ICM were 70.83%, 84.07%, 92.65% and 96.81%, but the specificity of liquid-based cytology was 91.91%. The sensitivity and specificity of a combination of liquid-based cytology and DNA-ICM were 84.09% and 85.78%, respectively. CONCLUSION: It is possible to use DNA-ICM technique as a primary screening method for esophageal squamous precancerous lesions.

[The distribution of the pre-cancerous condition and pathological changes of esophageal cancer of the community residents in high-incidence area].

OBJECTIVE: To observe the distribution of the pre-cancerous condition and pathological changes of esophageal cancer of the community residents in high-incidence area, and to provide etiological evidences for secondary prevention. METHODS: An iodine-staining endoscope census was conducted in 9536 residents with high-risk factors at Feicheng, a high esophageal cancer incidence community in Shandong province. Of which, 1507 pathologic biopsies were performed and chi2 test administrated. RESULTS: There was no statistical significance found in biopsy pathologic diagnosis between females and males among 1507 samples. The mild and medium atypical hyperplasia was taken as pre-cancerous condition and severe atypical hyperplasia was taken as pre-cancerous lesion. Taking all the population attending census as denominator, the detection rate of the precancerous state and precancerous lesion were 6.98% (294/4214) and 1.23% (52/4214) for the males, and 3.68% (196/5322) and 0.47% (25/5322) for the females, respectively. A statistical significance was observed when comparing males with females (chi2 were 52.349 and 15.267, respectively, P < 0.05). Analyzed by age group, severe atypical hyperplasia pathological changes were mainly distributed in the age group of 50- and 65-. The constituent ratio between 45 - and 50 - was the highest for CIS. Early carcinoma was mainly distributed in five age groups from 45- to 65-. It showed that high incidence town had a high detection rate of cancer and pathological changes of esophageal cancer in the analysis of urban and rural distribution. CONCLUSION: The distribution of the pre-cancerous state and pathological changes of esophageal cancer of the residents should have provided a scientific basis for the primary and secondary prevention.

[The risk factors related to esophageal squamous cell cancer in Feicheng county, China].

OBJECTIVE: To investigate the risk factors related to the esophageal squamous cell cancer in Feicheng county in Shandong province. METHODS: A case-control study was carried out in Feicheng county. There were two parts consisted in the cases. 253 cases, aged from 40 to 69 years old, were recruited from the screened endoscopic survey program from January 2004 to December 2006. The other part of cases was recruited from the people's Hospital of Feicheng city. 8159 subjects whose had normal endoscope test result were recruited as the control group. Besides cardiograph and ventral ultrasound examination the screening program also included an endoscope test during which mucosal stain with 1.2% iodine solution. The biopsies were taken from the screen and underwent pathologic evaluation by two pathologists; A self-administrative questionnaire survey was conducted in all the subjects to collect information about smoking, alcohol consumption and dietary. The binary Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (95% CI). The study protocol was approved by the local ethics committee and the study was conducted with the informed consents of all the study subjects. RESULTS: There were 235 esophageal cancers cases (70 identified in screening program, 183 were hospitalized patients) and 8159 controls in the case-control study. Three potential confounders were detected after univariate analysis. After adjusted the three confounders, age, sex and education, we found, smoking, alcohol drinking were the top ranked risk factors for esophageal cancer. When combing smoking and alcohol drinking, the or was 2.73 (95% CI: 1.54 - 4.82) for male, and the proportional attribute relative risk was 51.47%. We also observed that more dietary cellulose and vitamin C intake have protective effects. CONCLUSION: Smoking and alcohol drinking could increase the risk of esophageal cancer, and taking more dietary cellulose and vitamin C might decrease the risk.