Potential and application of abortive transcripts as a novel molecular marker of cancers.

Abortive transcript (AT) is a 2-19 nt long non-coding RNA that is produced in the abortive initiation stage. Abortive initiation was found to be closely related to RNA polymerase through in vitro experiments. Therefore, the distribution of AT length and the scale of abortive initiation are correlated to the promoter, discriminator, and transcription initiation sequence, and can be affected by transcription elongation factors. AT plays an important role in the occurrence and development of various diseases. Here we summarize the discovery of AT, the factors responsible for AT formation, the detection methods and biological functions of AT, to provide new clues for finding potential targets in the early diagnosis and treatment of cancers.

Comprehensive analysis of the protein phosphatase 2A regulatory subunit B56ε in pan-cancer and its role and mechanism in hepatocellular carcinoma.

BACKGROUND: B56ε is a regulatory subunit of the serine/threonine protein phosphatase 2A, which is abnormally expressed in tumors and regulates various tumor cell functions. At present, the application of B56ε in pan-cancer lacks a comprehensive analysis, and its role and mechanism in hepatocellular carcinoma (HCC) are still unclear. AIM: To analyze B56ε in pan-cancer, and explore its role and mechanism in HCC. METHODS: The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Profiling Interactive Analysis, and Tumor Immune Estimation Resource databases were used to analyze B56ε expression, prognostic mutations, somatic copy number alterations, and tumor immune characteristics in 33 tumors. The relationships between B56ε expression levels and drug sensitivity, immunotherapy, immune checkpoints, and human leukocyte antigen (HLA)-related genes were further analyzed. Gene Set Enrichment Analysis (GSEA) was performed to reveal the role of B56ε in HCC. The Cell Counting Kit-8, plate cloning, wound healing, and transwell assays were conducted to assess the effects of B56ε interference on the malignant behavior of HCC cells. RESULTS: In most tumors, B56ε expression was upregulated, and high B56ε expression was a risk factor for adrenocortical cancer, HCC, pancreatic adenocarcinoma, and pheochromocytoma and paraganglioma (all P < 0.05). B56ε expression levels were correlated with a variety of immune cells, such as T helper 17 cells, B cells, and macrophages. There was a positive correlation between B56ε expression levels with immune checkpoint genes and HLA-related genes (all P < 0.05). The expression of B56ε was negatively correlated with the sensitivity of most chemotherapy drugs, but a small number showed a positive correlation (all P < 0.05). GSEA analysis showed that B56ε expression was related to the cancer pathway, p53 downstream pathway, and interleukin-mediated signaling in HCC. Knockdown of B56ε expression in HCC cells inhibited the proliferation, migration, and invasion capacity of tumor cells. CONCLUSION: B56ε is associated with the microenvironment, immune evasion, and immune cell infiltration of multiple tumors. B56ε plays an important role in HCC progression, supporting it as a prognostic marker and potential therapeutic target for HCC.

Forkhead box C1 induces epithelial­mesenchymal transition and is a potential therapeutic target in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a highly invasive malignancy with cervical lymphopathy as the initial presentation. Epithelial­mesenchymal transition (EMT), a process by which epithelial cells lose cell­cell adhesion and gain migratory and invasive properties, has a pivotal role in metastasis. Forkhead box C1 (FoxC1), a member of the forkhead family of transcription factors, induces EMT and has a critical role in metastasis of multiple human cancers. However, the role of FoxC1 in the progression of NPC has remained elusive. The present study revealed that the expression of FoxC1 was markedly elevated in NPC tissues compared with that in chronically inflamed nasopharyngeal tissues and was closely correlated with vimentin, fibronectin and N­cadherin expression as indicated by immunohistochemical assays. In addition, high FoxC1 expression was positively associated with lymph node metastasis, distant metastasis and an advanced clinical stage in patients with NPC. Furthermore, FoxC1 expression was high in NPC cell lines while being low in an immortalized normal nasopharyngeal epithelial cell line. In vitro, knockdown of FoxC1 in the CNE2 human NPC cell line by small interfering RNA downregulated vimentin, fibronectin and N­cadherin expression and reduced the migratory and invasive capacity of CNE2 cells. In conclusion, the present study indicated that FoxC1 has a pivotal role in EMT through the upregulation of vimentin, fibronectin and N­cadherin expression. Thus, FoxC1 may be a potential therapeutic target in NPC.

Combined effects of six cytokine gene polymorphisms and SNP-SNP interactions on hepatocellular carcinoma risk in Southern Guangxi, China.

Cytokine gene single nucleotide polymorphisms (SNPs) are involved in the genesis and progression of hepatocellular carcinoma (HCC). We hypothesized that combined effects of cytokine gene SNPs and SNP-SNP interactions are associated with HCC risk. Six SNPs in cytokine genes (IL-2, IFN-γ, IL-1ß, IL-6, and IL-10) were genotyped in a study of 720 Chinese HCC cases and 784 cancer-free controls. Although none of these SNPs individually had a significant effect on the risk of HCC, we found that the combined effects of these six SNPs may contribute to HCC risk (OR=1.821, 95% CI=1.078-3.075). This risk was pronounced among smokers, drinkers, and hepatitis B virus carriers. A SNP-SNP interaction between IL-2-330 and IFN-γ-1615 was associated with an increased HCC risk (OR=1.078, 95% CI=1.022-1.136). In conclusion, combined effects of SNPs and SNP-SNP interactions in cytokine genes may contribute to HCC risk.

The benefits of psychosocial interventions for cancer patients undergoing radiotherapy.

BACKGROUND: Many patients with cancer experience depression and anxiety, and an associated decrease in quality of life (QOL) during radiation therapy (RT). The main objective of the study was to determine the benefits of psychosocial interventions for cancer patients who received RT. METHODS: Patients with cancer (n = 178) who agreed to participate in the study were randomized to the intervention arm (n = 89) or the control arm (n = 89). Patients in the intervention group received psychosocial care during RT, whereas the control group received RT only. The benefits of the intervention were evaluated using the Zung Self-rating Depression Scale (SDS) to measure depression, the Self-rating Anxiety Scale (SAS) to assess anxiety, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) to survey health-related QOL. The association between intervention and survival was also assessed. RESULTS: Patients randomly assigned to the intervention arm showed significant improvements on symptoms of depression (p < 0.05) and anxiety (p < 0.05), health-related QOL (p < 0.05) (i.e. better global health status, and physical and emotional functioning, and less insomnia) when compared with controls. In the subset analysis, female patients, those that received high dose irradiation, and those that underwent adjuvant chemotherapy could benefit more from psychosocial intervention. There was no difference between the two groups in disease-free survival (DFS) (2-year DFS 79.8% in the intervention arm and 76.4% in the control arm; p = 0.527) and overall survival (OS) (2-year OS 83.1% in the intervention arm and 84.3% in the control arm; p = 0.925) CONCLUSIONS: Psychosocial intervention is a cost-effective approach that can improve a patient's mood and QOL both during and after RT. However, the intervention was not found to reduce the risk of cancer recurrence and death. TRIAL REGISTRATION: ChiCTR-TRC-12002438.

[Relationship between hepatocellular carcinoma and the interaction between NQO1 polymorphisms and environmental factors].

OBJECTIVE: To study the relationship between hepatocellular carcinoma (HCC) and the interaction of polymorphisms in the NAD(P)H:quinone oxidoreductase (NQO1) gene with environmental factors using a hospital-based case-control study. FMETHODS: our-hundred newly diagnosed HCC cases and 400 healthy individuals (non-tumor controls) were enrolled in the study. Demographic information and medical history was obtained by questionnaire. TaqMan minor groove binder real-time PCR was carried out to detect the NQO1 C609T genotype using blood-derived DNA from all study participants. Unconditional logistic regression analysis was carried out to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The frequencies of NQO1 609 CC, CT and TT genotypes were 23.75%, 50.25% and 28.00% in the HCC group, and 37.55%, 43.75% and 18.25% in the control group. The differences between the HCC and control group reached statistical significance (all P less than 0.05). The ORs of NQO1 609 CT and TT genotypes were significantly higher compared to the CC genotype; the adjusted OR(95% CI) of CT was 2.106(1.137-3.110) and of TT was 2.564(1.357-4.744). Individuals carrying the NQO1 609 T allelic gene had a significantly higher risk of HCC than those carrying the C allelic gene; the adjusted OR(95% CI) was 1.86(1.235-2.980). Interactions were found between hepatitis B virus infection with hepatitis B surface antigen (HBsAg)-positivity and NQO1 gene polymorphisms (adjusted OR: 2.431) and history of cancer (adjusted OR: 8.3592). CONCLUSION: The NQO1 C609T genotype is associated with increased risk of HCC. Interactions between HBsAg-positive infection, history of cancer, and NQO1 gene polymorphisms may contribute to HCC.

[Application of multi-coeffieient of variation significance test for toxicology study].

OBJECTIVE: To establish the methods of calculating and analyzing the multi-coefficient of variation significance test for the toxicology study. METHODS: The paper aimed to confirm the significance level with the method of Bonferroni and then compared the methods of calculating and analyzing of the experiment groups with the control group respectively. RESULTS: The significance level of multi-coefficient of variation significance test was confirmed as alpha1=0.0167. Compared with the control groups, the activity of ALT in serum both in 30 mg/kg and 60 mg/kg groups did not change in the average significance test, which was not statistically significant (P>0.05), while it changed in the variation significance test, which was of statistical significance (P<0.0167). The activity of AST in serum in 60 mg/kg group did not change in the average significance test (P>0.05), while it changed in the variation significance test (P<0.0167). CONCLUSION: The complete changes of the indexes can only be shown by use of both the average significance test and the variation significance test together.

[Etiologic fraction and interaction of risk factors for primary hepatic carcinoma in Guangxi, China].

OBJECTIVE: To explore etiologic fraction (EF) and interaction of hepatitis B virus (HBV) infection and other risk factors for primary hepatocellular carcinoma (PHC) in Guangxi, China. METHODS: A hospital-based case-control study including 500 PHC patients and 500 nontumorous patients was carried out in Guangxi. EF and interactions of HBV infection and other risk factors for PHC were analyzed by crossover analysis and nonconditional multiple logistic regression. RESULTS: HBV infection, family history of PHC, diabetes mellitus, eating raw fish, heavy alcohol consumption, frequently used drug, low income, mental oppression and blood type B all were risk factors for PHC. With EFs of 0.725, 0.186, 0.119, 0.486, 0.385, 0.438, 0.277, 0.607, 0.299, respectively and with etiologic fractions attributable to interaction [EF(A xB)] of 0.736, 0.643, 0.849, 0.551, 0.592, 0.618, 0.902, 0.577; and indices of interaction of 0.743, 0.651, 0.853, 0.560, 0.600, 0.626, 0.907, 0.586, respectively. CONCLUSION: Main risk factors for PHC might include HBV infection, family history of PHC, diabetes mellitus, eating raw fish, heavy alcohol consumption, frequently used drug, low income, mental oppression and blood type B. HBV infection with other risk factors might exert synergistic action on developing PHC and increase the risk of PHC.

[Synergistic effect of HBV infection, alcohol and raw fish consumption on oncogenisis of primary hepatic carcinoma].

OBJECTIVE: To study the correlation of eating raw fish with primary hepatic carcinoma (PHC), and to investigate the synergistic effect of HBV infection, alcohol consumption and eating raw fish on the oncogenesis of PHC. METHODS: A hospital-based case-control study was conducted among 500 PHC patients and 500 non-cancerous patients in order to compare the history of eating raw fish. The synergistic pathogenetic action of eating raw fish, HBV infection and alcohol consumption on carcinogenesis of PHC was analyzed by crossover analysis and multiple logistic regression. RESULTS: The rates of eating raw fish in the past between the case (54.8%) and the control group (8.4%) were significantly different (P < 0.001). OR value of suffering PHC in the patients who ate raw fish in the past was 13.6 (95% CI: 9.1-19.5) when compared with the non-cancerous patient. HBV infection, alcohol consumption and eating raw fish showed an interactive effect on the development of PHC, with a relative excessive risk of interaction(RERI) of 195.3 and 17.8; attributable proportion of interaction (API) of 0.8630 and 0.5251; and synergy index (S) of 7.5 and 2.8, respectively. CONCLUSION: A history of eating raw fish may be an important risk factor for suffering primary hepatic carcinoma. HBV infection, alcohol consumption and eating raw fish may have a synergistic effect on the developing of primary hepatic carcinoma.

[Evaluation of the risk of clonorchiasis inducing primary hepatocellular carcinoma].

OBJECTIVE: To explore the relationship between clonorchiasis and primary hepatocellular carcinoma (HCC) and analyze the synergistic actions of HBV infection, alcohol consumption and clonorchiasis on HCC development. METHODS: This hospital-based case-control study was conducted among 444 HCC patients (cases) and 500 non tumor patients (controls) to compare the prevalence of clonorchiasis in the cases and the controls. The risk of clonorchiasis and the synergistic actions between HBV infection, alcohol consumption and clonorchiasis on HCC development were analyzed by crossover analysis and multiple logistic regression. RESULTS: The prevalence of clonorchiasis in the cases (16.44%) was much higher than that of the controls (2.40%) (X2 = 56.58, P less than 0.01). In the case group, the OR value of those with clonorchiasis was 8.00 (95% CI: 4.34-14.92). The OR value was 4.82 (95% CI: 2.32-10.26) for the subjects whose clonorchiasis was diagnosed less than 10 years before their diagnosis of HCC, and was 17.54 (95% CI: 5.47-57.18) for those whose HCC was diagnosed more than 10 years ago. HBV infection, alcohol consumption and clonorchiasis showed an additive interaction in the development of HCC, with a relative excess risk of interaction of 110.43 and 18.23; attributable proportion of interaction of 0.80 and 0.63; synergy index of 5.18 and 2.84, respectively. CONCLUSION: Clonorchiasis could be an important risk factor for HCC. When the course of clonorchiasis is prolonged, the risk of HCC could increase. HBV infection, alcohol consumption and clonorchiasis might have synergistic actions on the development of HCC.