Self-management challenges and support needs among patients with primary glaucoma: a qualitative study.

BACKGROUND: Self-management plays an important role in the disease management of glaucoma patients. The effectiveness of the program can be improved by assessing the patient's perspective and needs to tailor self-management support. Most studies have focused on assessing one of these self-management behaviours, such as medication adherence, and there is a lack of systematic assessment of the support needs and challenges of self-management for patients with glaucoma. Therefore, in this study, we conducted an in-depth investigation into the self-management challenges and support needs of patients with primary glaucoma, providing a basis for nursing staff to implement self-management support. METHOD: The phenomenological method and semistructured interviews were used in this study. A total of 20 patients with primary glaucoma were recruited between June and December 2022. Colaizzi's analysis method was used to analyse the interview data. RESULTS: Challenges for patients include becoming an expert in glaucoma, managing negative emotions, adapting to daily life changes and resuming social activities. To address these challenges, four themes of patient self-management support needs were identified: (1) health information support, (2) social support, (3) psychological support, and (4) daily living support. CONCLUSION: Patients with primary glaucoma experience varying degrees of challenge in dealing with medical, emotional, and social aspects. Comprehending the support needs of patients, healthcare professionals should deliver targeted, personalized and comprehensive self-management interventions to enhance their capacity of patients to perform self-management and improve their quality of life.

Wogonin alleviates liver injury in sepsis through Nrf2-mediated NF-κB signalling suppression.

Sepsis is a life-threatening organ dysfunction syndrome, and liver is a susceptible target organ in sepsis, because the activation of inflammatory pathways contributes to septic liver injury. Oxidative stress has been documented to participate in septic liver injury, because it not only directly induces oxidative genotoxicity, but also exacerbates inflammatory pathways to potentiate damage of liver. Therefore, to ameliorate oxidative stress is promising for protecting liver in sepsis. Wogonin is the compound extracted from the medicinal plant Scutellaria baicalensis Geogi and was found to exert therapeutic effects in multiple inflammatory diseases via alleviation of oxidative stress. However, whether wogonin is able to mitigate septic liver injury remains unknown. Herein, we firstly proved that wogonin treatment could improve survival of mice with lipopolysaccharide (LPS)- or caecal ligation and puncture (CLP)-induced sepsis, together with restoration of reduced body temperature and respiratory rate, and suppression of several pro-inflammatory cytokines in circulation. Then, we found that wogonin effectively alleviated liver injury via potentiation of the anti-oxidative capacity. To be specific, wogonin activated Nrf2 thereby promoting expressions of anti-oxidative enzymes including NQO-1, GST, HO-1, SOD1 and SOD2 in hepatocytes. Moreover, wogonin-induced Nrf2 activation could suppress NF-κB-regulated up-regulation of pro-inflammatory cytokines. Ultimately, we provided in vivo evidence that wogonin activated Nrf2 signalling, potentiated anti-oxidative enzymes and inhibited NF-κB-regulated pro-inflammatory signalling. Taken together, this study demonstrates that wogonin can be the potential therapeutic agent for alleviating liver injury in sepsis by simultaneously ameliorating oxidative stress and inflammatory response through the activation of Nrf2.

Genetic variations in base excision repair pathway and risk of bladder cancer: a case-control study in the United States.

Base excision repair (BER) is one of the major cellular DNA repair pathways that repairs small isolated foci of DNA damage including reduced or oxidized single bases or fragments and small, non-bulky adducts. Genetic variations in BER genes may affect DNA repair capacity and increase susceptibility to bladder cancer. In a case-control study of 801 bladder cancer patients and 801 matched controls, we evaluated the associations of 167 single nucleotide polymorphisms (SNPs) from 19 genes of the BER pathway with the risk of bladder cancer. In individual SNP analysis, 13 SNPs in 10 BER pathway genes were significantly associated with bladder cancer risk. The most significant SNP was rs2029167 in the SMUG1 gene. The homozygous variant GG genotype was associated with a 1.42-fold increased risk of bladder cancer (95% confidence interval [CI], 1.11-1.82, P=0.005). Cumulative effect analysis showed joint effects of increased risk of bladder cancer with increasing number of unfavorable genotypes in patients. Classification and regression tree analysis further revealed high-order gene-gene interactions and categorized the study subjects into low-, medium-low-, medium-high-, and high-risk groups. Compared with the low-risk group, the odds ratio for medium-low-, medium-high-, and high-risk group was 1.83 (95% CI: 1.23-2.72), 2.61 (95% CI: 1.79-3.80), and 3.05 (95% CI: 2.08-4.46), respectively (P for trend<0.001). Our results suggest that genetic variations in BER pathway genes modulate the risk of bladder cancer individually and jointly.

Functional polymorphisms of ATP citrate lyase gene predicts clinical outcome of patients with advanced colorectal cancer.

BACKGROUND: Previous studies have demonstrated that ATP citrate lyase (ACLY) plays an important role in the development of many cancers. Our current study aims to assess the effects of functional single nucleotide polymorphisms (SNPs) in ACLY gene on recurrence and survival of colorectal cancer (CRC) patients. METHODS: A total of 697 resected Chinese CRC patients were included in this study. Two functional single nucleotide polymorphisms in ACLY gene were examined using the Sequenom iPLEX genotyping system. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the prognosis analysis. RESULTS: Multivariate Cox regression analysis showed that there was no significant association between SNPs in ACLY gene and the prognosis of total patient cohort. However, in patients with stage III + IV diseases, the two functional SNPs (rs2304497 and rs9912300) exhibited a significant association with the risks of death (HR = 0.47, 95% CI = 0.24-0.90 and HR = 0.59, 95% CI = 0.37-0.92, respectively) and recurrence (HR = 0.46, 95% CI = 0.24-0.86 and HR = 0.54, CI = 0.35-0.83, respectively). Kaplan-Meier analysis indicated that those CRC patients carrying heterozygous (WV) or homozygous variant (VV) genotypes in rs2304497 and rs9912300 had significantly better overall survival (OS) and recurrence-free survival (RFS). Moreover, we observed remarkable cumulative effects of these two SNPs on overall survival and recurrence-free survival (P for trend = 0.012 and 0.003, respectively). Compared with patients carrying zero unfavorable genotype, those carrying two unfavorable genotypes had a 2.24-fold and 2.33-fold increase of death and recurrence risks, respectively. CONCLUSIONS: The SNPs in ACLY gene may serve as independent prognostic markers for patients with advanced stage CRC.

Current Status of Shared Decision-Making in Intraocular Lens Selection for Cataract Surgery: A Cross-Sectional Study.

Purpose: To explore 1) the level of shared decision-making (SDM) participation in intraocular lens (IOL) selection in cataract patients and the factors that influence this participation and 2) the relationships between preparation for decision-making (PrepDM)and the level of SDM participation and satisfaction with the decision (SWD). Provide guidance for improving SDM in ophthalmology. Patients and Methods: 176 cataract patients were asked to complete the PrepDM scale, the 9-item Shared Decision Making Questionnaire (SDM-Q-9) and the SWD instrument in IOL decision-making process. Multiple linear regression was used to analyze the influencing factors of the level of SDM. The Process program and bootstrap sampling method was used to test whether the level of participation in SDM was a mediating variable among the three. Results: The SDM-Q-9 median score was 77.78 (IQR 31.11-88.89). Patients with a history of surgery in the operative eye (P=0.022) or PrepDM <60 points (P<0.001) had lower SDM-Q-9 scores than patients with no history of surgery in the operative eye or PrepDM ≥60 points. Patients with an education level lower than primary school had lower SDM-Q-9 scores than patients with other education levels (P<0.05). The PrepDM of cataract patients was positively correlated with the level of SDM (r=0.768, P<0.001) and with the SWD (r=0.727, P<0.001), and the level of SDM was positively correlated with the SWD (r=0.856, P<0.001). The level of SDM fully mediated PrepDM and SDW, with a mediating effect value of 0.128 and a mediating effect of 86.66% of the total effect. Conclusion: The SDM of cataract patients involved in IOL selection was in the upper middle range. Education, history of surgery in the operated eye, and PrepDM were factors that influenced the level of SDM. The level of participation in SDM fully mediated the relationship between PrepDM and SWD.

CD147 induces angiogenesis through a vascular endothelial growth factor and hypoxia-inducible transcription factor 1α-mediated pathway in rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is an inflammatory and angiogenic disease. However, the molecular mechanisms that promote angiogenesis in RA have not been clearly identified. Our objective was to study the role of CD147 in angiogenesis and determine whether the strategy in which CD147 is suppressed might be useful in reducing angiogenesis in RA. METHODS: Correlations among expression levels of CD147, vascular endothelial growth factor (VEGF), and hypoxia-inducible factor 1α (HIF-1α) were determined by immunohistochemistry staining. RA fibroblast-like synoviocytes (FLS) cells were cultured under various conditions, and the production of VEGF and HIF-1α was examined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The SCID mouse coimplantation model of RA (SCID-HuRAg) was established, mice were treated with CD147 monoclonal antibody, infliximab, or both CD147 and infliximab, and the volume of the grafts and the average vascular density were measured and analyzed. Western blot analyses were performed to examine the potential signaling pathways. RESULTS: The expression levels of CD147 showed significantly positive correlations with VEGF and HIF-1α levels, as well as with vascular density, in RA synovium. After small interfering RNA transfection or after addition of specific antibodies for CD147, the production of VEGF and HIF-1α were significantly reduced. The expression of VEGF and HIF-1α decreased more after CD147 inhibition than after infliximab treatment in the engrafted tissues in SCID-HuRAg mice. The phosphatidylinositol 3-kinase/Akt pathway may be involved in this process. CONCLUSION: CD147 induces up-regulation of VEGF and HIF-1α in RA FLS, further promotes angiogenesis, and leads to the persistence of synovitis. Inhibition of CD147 may be a promising target for novel therapeutic strategies.

High-Throughput Electromechanical Coupling Chip Systems for Real-Time 3D Invasion/Migration Assay of Cells.

Cell invasion/migration through three-dimensional (3D) tissues is not only essential for physiological/pathological processes, but a hallmark of cancer malignancy. However, how to quantify spatiotemporal dynamics of 3D cell migration/invasion is challenging. Here, this work reports a 3D cell invasion/migration assay (3D-CIMA) based on electromechanical coupling chip systems, which can monitor spatiotemporal dynamics of 3D cell invasion/migration in a real-time, label-free, nondestructive, and high-throughput way. In combination with 3D topological networks and complex impedance detection technology, this work shows that 3D-CIMA can quantitively characterize collective invasion/migration dynamics of cancer cells in 3D extracellular matrix (ECM) with controllable biophysical/biomechanical properties. More importantly, this work further reveals that it has the capability to not only carry out quantitative evaluation of anti-tumor drugs in 3D microenvironments that minimize the impact of cell culture dimensions, but also grade clinical cancer specimens. The proposed 3D-CIMA offers a new quantitative methodology for investigating cell interactions with 3D extracellular microenvironments, which has potential applications in various fields like mechanobiology, drug screening, and even precision medicine.

GWAS-identified colorectal cancer susceptibility loci associated with clinical outcomes.

Recent genome-wide association studies (GWAS) have identified several common susceptibility loci associated with the risk of colorectal cancer (CRC). However, whether these loci affect clinical outcomes of CRC is not clear. In this study, we genotyped 26 single nucleotide polymorphisms (SNPs) in 10 GWAS-identified CRC susceptibility regions and evaluated their associations with survival and recurrence in 285 stage II and III patients receiving fluorouracil-based adjuvant chemotherapy. Only one SNP, rs10318 (15q13.3), was significantly associated with recurrence for patients with stage II disease. Three SNPs: rs10749971 (11q23.1), rs961253 (20p12.3) and rs355527 (20p12.3) in two regions were significantly associated with recurrence for patients with stage III disease. Five SNPs: rs961253 (20p12.3), rs355527 (20p12.3), rs4464148 (18q21.1), rs6983267 (8q24.21) and rs10505477 (8q24.21) in three regions were significantly associated with survival for patients with stage III disease. Cumulative effects of multiple unfavorable genotypes were observed for recurrence and survival in patients with stage III CRC. Our results suggest that cancer susceptibility loci may also affect the prognosis of CRC patients receiving fluorouracil-based adjuvant chemotherapy.

Bibliometric analysis of the global research trends and hotspots in chordoma from 2000 to 2020.

INTRODUCTION: Chordoma is formed from embryonic residues or ectopic chordae and locally aggressive or malignant tumors. We visually analyzed the research tendency and hotspot of chordoma. METHODS: The bibliometric analysis was conducted from the Web of Science Core Collection database over the past two decades. The term and strategies were as follows: "TS = (chordoma) OR TS = (chordoblastoma) OR TS = (chordocarcinoma) OR TS = (chordoepithelioma) OR TS = (chordosarcoma) OR TS = (notochordoma). AND Language: English. AND Reference Type: Article OR Review". A total of 2,118 references were retrieved and used to make a visual analysis by VOSviewer 1.6.15. RESULTS: The chordoma was on a steady rise and chordoma but remained the focus of scholars and organizations over the last two decades. The Chinese institutions and scholars lacked cooperation with their counterparts in other countries. The citations of documents and co-citation analysis of cited references suggested that M.L. McMaster, B.P. Walcott, P. Bergh, and S. Stacchiotti were leading researchers in this field of chordoma and their papers had been widely accepted and inspired recent researches. Keywords associated with recent chemotherapy, PD-1-related immunotherapy, and SMARCB1/integrase interactor 1 (INI1) in chordoma were a shortage of research and there may be more research ideas in the future by scholars. The research of chordoma will continue to be the hotspot. CONCLUSIONS: Thus, explaining the molecular mechanism and potential role of transcriptional inhibition and immunologic responses to SMARCB1/INI1-negative poorly differentiated chordoma will be available for preclinical experiments and clinical trials and lead to new therapeutic opportunities for chordoma patients.

A nanohybrid synthesized by polymeric assembling Au(I)-peptide precursor for anti-wrinkle function.

A major sign of aging is wrinkles (dynamic lines and static lines) on the surface of the skin. In spite of Botulinum toxin's favorable therapeutic effect today, there have been several reports of its toxicity and side effects. Therefore, the development of an effective and safe wrinkle-fighting compound is imperative. An antioxidant-wrinkle effect was demonstrated by the peptide that we developed and synthesized, termed Skin Peptide. Aiming at the intrinsic defects of the peptide such as hydrolysis and poor membrane penetration, we developed a general approach to transform the Skin Peptide targeting intracellular protein-protein interaction into a bioavailable peptide-gold spherical nano-hybrid, Skin Pcluster. As expected, the results revealed that Skin Pcluster reduced the content of acetylcholine released by neurons in vitro, and then inhibit neuromuscular signal transmission. Additionally, human experiments demonstrated a significant de-wrinkle effect. Moreover, Skin Pcluster is characterized by a reliable safety profile. Consequently, anti-wrinkle peptides and Skin Pcluster nanohybrids demonstrated innovative anti-wrinkle treatments and have significant potential applications.

Expression of CD147 (EMMPRIN) on neutrophils in rheumatoid arthritis enhances chemotaxis, matrix metalloproteinase production and invasiveness of synoviocytes.

The occurrence of neutrophils at the pannus-cartilage border is an important phenomenon for understanding the pathogenesis of rheumatoid arthritis (RA). Matrix metalloproteinases (MMPs) are predominant enzymes responsible for the cartilage degradation. The present article studied the expression of CD147 on neutrophils and its potential role in neutrophil chemotaxis, MMPs production and the invasiveness of fibroblast-like synoviocytes (FLS). The results of flow cytometry revealed that the mean fluorescence intensity of CD147 expression on neutrophils of peripheral blood from RA patients was higher than that in healthy individual. The potential role of CD147 in cyclophilin A (CyPA)-mediated cell migration was studied using chemotaxis assay and it was found that the addition of anti-CD147 antibody significantly decreased the chemotactic index of the neutrophils. Significantly elevated release and activation of MMPs were seen in the co-culture of neutrophil and FLS compared with cultures of the cells alone. An increased number of cells invading through the filters in the invasion assays were also observed in the co-cultured cells. The addition of anti-CD147 antibody had some inhibitory effect, not only on MMP production but also on cell invasion in the co-culture model. Our study demonstrates that the increased expression of CD147 on neutrophils in RA may be responsible for CyPA-mediated neutrophil migration into the joints, elevated MMPs secretion and cell invasion of synoviocytes, all of which may contribute to the cartilage invasion and bone destruction of RA. Better knowledge of these findings will hopefully provide a new insight into the pathogenesis of RA.

Annexin II promotes invasion and migration of human hepatocellular carcinoma cells in vitro via its interaction with HAb18G/CD147.

HAb18G/CD147, a member of the immunoglobulin family enriched on the surface of tumor cells, is reported to be correlated with invasion, metastasis, growth, and survival of malignant cells. Here, we found that annexin II, a 36-kDa Ca(2+)- and phospholipid-binding protein and in vivo substrate for tyrosine kinase and PKC, is a new interaction protein of HAb18G/CD147 in human hepatocellular carcinoma (HCC) cells. In the present study, we explored the unclear role of annxin II in HCC invasion and migration and the interaction effects between HAb18G/CD147 and annexin II. Our data show that downregulation of annexin II in HCC cells significantly decreased the secretion of MMP, migration ability, and invasive potential, and affected the cytoskeleton rearrangement of tumor cells. The MMP-2 level and invasive potential of HCC cells were regulated by both annexin II and HAb18G/CD147. Also, interaction effects exist between the two molecules in tumor progression, including MMP-2 production, migration, and invasion. These results suggest that annexin II promotes the invasion and migration of HCC cells in vitro, and annexin II and HAb18G/CD147 interact with each other in the same signal transduction pathway working as a functional complex in tumor progression.

The interaction of HAb18G/CD147 with integrin alpha6beta1 and its implications for the invasion potential of human hepatoma cells.

BACKGROUND: HAb18G/CD147 plays pivotal roles in invasion by hepatoma cells, but the underlying mechanism remains unclear. Our previous study demonstrated that overexpression of HAb18G/CD147 promotes invasion by interacting with integrin alpha3beta1. However, it has never been investigated whether alpha3beta1 is solely responsible for this process or if other integrin family members also interact with HAb18G/CD147 in human hepatoma cells. METHODS: Human SMMC-7721 and FHCC98 cells were cultured and transfected with siRNA fragments against HAb18G/CD147. The expression levels of HAb18G/CD147 and integrin alpha6beta1 were determined by immunofluorescent double-staining and confocal imaging analysis. Co-immunoprecipitation and Western blot analyses were performed to examine the native conformations of HAb18G/CD147 and integrin alpha6beta1. Invasion potential was evaluated with an invasion assay and gelatin zymography. RESULTS: We found that integrin alpha6beta1 co-localizes and interacts with HAb18G/CD147 in human hepatoma cells. The enhancing effects of HAb18G/CD147 on invasion capacity and secretion of matrix metalloproteinases (MMPs) were partially blocked by integrin alpha6beta1 antibodies (P < 0.01). Wortmannin, a specific phosphatidylinositol kinase (PI3K) inhibitor that reverses the effect of HAb18G/CD147 on the regulation of intracellular Ca2+ mobilization, significantly reduced cell invasion potential and secretion of MMPs in human hepatoma cells (P < 0.05). Importantly, no additive effect between Wortmannin and alpha6beta1 antibodies was observed, indicating that alpha6beta1 and PI3K transmit the signal in an upstream-downstream relationship. CONCLUSION: These results suggest that alpha6beta1 interacts with HAb18G/CD147 to mediate tumor invasion and metastatic processes through the PI3K pathway.

Silencing of calpain expression reduces the metastatic potential of human osteosarcoma cells.

Osteosarcoma, the most common primary bone tumor in young adults, is characterized by local invasion and distant metastasis. But detailed mechanisms of tumorigenicity and metastasis of osteosarcoma are not well known. We report the involvement of calpains, a family of calcium-activated, cysteine proteases, in the invasive and metastatic processes of human osteosarcoma cells. By using siRNA treatment, the expression of mu- and m-calpains were downregulated in human Saos-2 osteosarcoma cells. Both the adhesive and invasive potentials were significantly attenuated in calpain siRNA-transfected human Saos-2 osteosarcoma cells. MMPs are the main factors involved in malignant tumor invasion and metastasis. siRNA of calpains also significantly inhibited the secretion of MMP-2 in Saos-2 cells. These results suggest that mu- and m-calpains are important in the invasion and metastasis of human osteosarcoma cells, and calpains might be targeted to reduce tumor progression.

Sestrin 2 confers primary resistance to sorafenib by simultaneously activating AKT and AMPK in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the malignancy derived from normal hepatocytes with increasing incidence and extremely poor prognosis worldwide. The only approved first-line systematic treatment agent for HCC, sorafenib, is capable to effectively improve advanced HCC patients' survival. However, it is gradually recognized that the therapeutic response to sorafenib could be drastically diminished after short-term treatment, defined as primary resistance. The present study is aimed to explore the role of stress-inducible protein Sestrin2 (SESN2), one of the most important sestrins family members, in sorafenib primary resistance. Herein, we initially found that SESN2 expression was significantly up-regulated in both HCC cell lines and tissues compared to normal human hepatocytes and corresponding adjacent liver tissues, respectively. In addition, SESN2 expression was highly correlated with sorafenib IC50 of HCC cell lines. Thereafter, we showed that sorafenib treatment resulted in an increase of SESN2 expression and the knockdown of SESN2 exacerbated sorafenib-induced proliferation inhibition and cell apoptosis. Further mechanistic study uncovered that SESN2 deficiency impaired both AKT and AMPK phosphorylation and activation after sorafenib treatment. Moreover, the correlations between SESN2 expression and both phosphor-AKT and phosphor-AMPK expression were illustrated in HCC tissues. Taken together, our study demonstrates that SESN2 activates AKT and AMPK signaling as a novel mechanism to induce sorafenib primary resistance in HCC.

[Sestrin 2(SESN2) promotes primary resistance to sorafenib by activating AKT in hepatocellular carcinoma cells].

Objective To explore the role of sestrin2 (SESN2) in sorafenib primary resistance and the underlying mechanism in hepatocellular carcinoma (HCC) cells. Methods Real-time quantitative PCR (qRT-PCR) and Western blot analysis were performed to examine SESN2 mRNA and protein levels in Bel-7404, SNU-398, HLE, HLF and Hep3B cell lines. Immunohistochemical staining was used to detect SESN2 expression in HCC tissues. After the treatment of 0, 2, 5, 10, 15, 20, 25 µmol/L sorafenib for 24 hours, CCK-8 assay was performed to detect the cell viability and subsequent IC50 of sorafenib in the above HCC cell lines. After the treatment of 0, 2, 4, 6, 8 µmol/L sorafenib for 24 hours, qRT-PCR and Western blot analysis were conducted to measure the alterations of SESN2 mRNA and protein expressions in Bel-7404 and SNU-398 cells. CCK-8 assay and flow cytometry were performed to examine the viability and apoptosis of Bel-7404 and SNU-398 cells after sorafenib treatment with or without SESN2 knockdown by siRNA transfection. Western blot analysis was used to test the expressions of AKT and phosphorylated-AKT. Results Compared with the control, SESN2 expression markedly increased in both HCC cell lines and tissues and there was a positive correlation between SESN2 expression and IC50 of sorafenib in different HCC cell lines. Subsequently, the mRNA and protein levels of SESN2 were significantly elevated after sorafenib treatment in Bel-7404 and SNU-398 cells, and SESN2 knockdown led to decreased cell viability and increased cell apoptosis after sorafenib treatment. More importantly, SESN2 knockdown impaired sorafenib-induced AKT activation in HCC cells. Conclusion SESN2 up-regulation conferred primary resistance to sorafenib by activating AKT in HCC cells.

Genetic variants in de novo lipogenic pathway genes predict the prognosis of surgically-treated hepatocellular carcinoma.

Over-expression of de novo lipogenesis (DNL) pathway genes is associated with the prognosis of various types of cancers. However, effects of single nucleotide polymorphisms (SNPs) in these genes on recurrence and death of hepatocellular carcinoma (HCC) patients after surgery are still unknown. A total of 492 primary HCC patients treated with surgery were included in this study. Nine SNPs in 3 genes (ACACA, FASN and ACLY) of DNL pathway were genotyped. Multivariate Cox proportional hazard regression model and Kaplan-Meier curve were used to analyze the association of SNPs with clinical outcomes. Two SNPs in ACACA gene were significantly associated with overall survival of HCC patients. Patients carrying homozygous variant genotype (VV) in rs7211875 had significantly increased risk of death, while patients carrying VV genotype in rs11871275 had significant decreased risk of death, when compared with those carrying homozygous wild-type or heterozygous genotypes. Moreover, patients carrying VV genotype in rs11871275 had decreased recurrence risk, while patients carrying variant genotype in rs4485435 of FASN gene had increased recurrence risk. Further cumulative effect analysis showed significant dose-dependent effects of unfavorable SNPs on both death and recurrence. SNPs in DNL genes may serve as independent prognostic markers for HCC patients after surgery.

Polymorphisms in genes of the de novo lipogenesis pathway and overall survival of hepatocellular carcinoma patients undergoing transarterial chemoembolization.

Aberrant expression of genes in de novo lipogenesis (DNL) pathway were associated with various cancers, including hepatocellular carcinoma (HCC). Single nucleotide polymorphisms (SNPs) of DNL genes have been reported to be associated with prognosis of some malignancies. However, the effects of SNPs in DNL genes on overall survival of HCC patients receiving transarterial chemoembolization (TACE) treatment are still unknown. In present study, nine SNPs in three genes (ACLY, ACACA and FASN) in DNL pathway were genotyped using the Sequenom iPLEX genotyping system in a hospital-based cohort with 419 HCC patients treated with TACE, and their associations with HCC overall survival were evaluated by Cox proportional hazard regression analysis under three genetic models (additive, dominant and recessive). Although we did not find any significant results in total analysis (all p>0.05), our stratified data showed that SNP rs9912300 in ACLY gene was significantly associated with overall survival of HCC patients with lower AFP level and SNP rs11871275 in ACACA gene was significantly associated with overall survival of HCC patients with higher AFP level. We further identified the significant interactions between AFP level and SNP rs9912300 or rs11871275 in the joint analysis. Conclusively, our data suggest that genetic variations in genes of DNL pathway may be a potential biomarker for predicting clinical outcome of HCC patients treated with TACE.

Genetic variations in IDH gene as prognosis predictors in TACE-treated hepatocellular carcinoma patients.

Metabolic reprogramming is an important hallmark of cancer cells, including the alterations of activity and expression in tricarboxylic acid (TCA) cycle key enzymes. Previous studies have reported the associations between tumor formation and three core enzymes involved in the TCA cycle. However, the association between functional single nucleotide polymorphisms (SNPs) in one of TCA cycle key gene isocitrate dehydrogenase (IDH) and the overall survival of hepatocellular carcinoma (HCC) patients treated with transcatheter arterial chemoembolization (TACE) has never been investigated. Five functional SNPs in IDH1 and IDH2 genes were genotyped using the Sequenom iPLEX genotyping system in a cohort of 419 unresectable Chinese HCC patients treated with TACE. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the prognosis analysis. We found that SNPs rs12478635 in IDH1 and rs11632348 in IDH2 gene exhibited significant associations with death risk in HCC patients in the dominant model (HR 1.33; 95 % CI 1.02-1.73; P = 0.037) and in recessive model (HR 1.87; 95 % CI 1.27-2.75; P = 0.001), respectively. Moreover, we observed a cumulative effect of these two SNPs on HCC overall survival, indicating a significant trend of death risk increase with increasing number of unfavorable genotypes (P for trend = 0.001). Additionally, our data suggest that unfavorable genotypes of two SNPs may be used as an independent prognostic marker in those with advanced stage and patients with serum AFP <200 µg/L. Our results for the first time suggest that IDH gene polymorphisms may serve as an independent prognostic marker for HCC patients treated with TACE.