Backgrouds: Whether homologous recombination repair (HRR) mutation has a differential effect on the prognosis has not been confirmed by current studies. The purpose of this study was to explore the clinical importance, prognostic value, and frequency of pathogenic changes in HRR genes in patients with ovarian cancer (OC). Methods: We analyze information including HRR mutation and clinical prognosis of OC patients both in our cohort and in the TCGA-OV database. Blood and/or tumor samples from 98 women admitted to Shanghai General Hospital between January 2021 and May 2024, and DNA sequencing was performed on these samples for all patients included in this retrospective study. Testing was performed for HRR mutations, including germline BRCA1/2 mutations, and defects in HRR were defined as detrimental mutations within relevant genes. Comprehensive medical records were gathered for all patients, with a follow-up period recorded for 74 of them. Results: HRR pathway genes, including BRCA1/2, CDK12, RAD54L, RAD51, ATM, MRE11, and BRIP2, are highly expressed in FIGO Stages I-II OCs among 482 patients in the TCGA-OV database, and 95.06% samples presented mutations. The alignment diagram analyzed by logistic and Cox regression was derived to investigate HRR genes on overall survival (OS < 763 days) of OC patients. A total of 98 patients were enrolled in our study, with 70 harboring HRR mutations (HRRmt) and 28 having the HRR wild-type (HRRwt). The predominant pathological type across all four patient groups was high-grade serous adenocarcinoma, with similar prevalence in HRRmt (84.30%) versus HRRwt (75%, p=0.360) and BRCAmt (94.20%) versus BRCAwt (74.60%, p=0.151) groups. Survival prediction data were collected from 74 patients, and the HRRmt group (n = 50) exhibited a numerically longer PFS compared to the HRRwt group (n = 24), with 23 months versus 17 months, respectively. A significant disparity was noted in the percentage of patients administered PARPi medication between the HRRmt and HRRwt groups (58.00% vs. 20.20%; p=0.003). Patients in both the HRRmt group (p=0.049) and the BRCAwt group (p=0.046) receiving PARPi treatment have extended PFS. Significant differences were identified between HRRmt and HRRwt groups in the size of the initial debulking surgery achieving R0 status (p=0.005), low CA125 levels (< 1000 U/mL) at diagnosis (p=0.015), and the use of PARP inhibitors (PARPi) (p=0.024) and antiangiogenic drugs (p < 0.001). For patients with HRR mutations, the use of PARPi significantly impacted PFS (p=0.049), and achieving R0 status (p=0.005) significantly influenced PFS. Conclusions: This study indicates that mutations in the HRR gene possess significant potential as a prognostic marker in OC. Our aim was to comprehensively explore how HRR gene mutations, including but not limited to BRCA, might influence the clinical course and survival of patients, shedding light on potential new avenues for personalized treatment strategies.

Supplementary Figures S1-S3; Supplementary Tables S1-S4.

BACKGROUND:Gastric cancer (GC) is one of the most common cancers causing a poor prognosis worldwide. HOXA13, as a member of the homeobox (HOX) family, is involved in the regulation of cancer progression and has attracted increasing attention, as a potential novel target for anticancer strategies. However, the significance of HOXA13 in GC remains unclear. This article aims to explore the potential mechanism of HOXA13 in GC progression.METHODS:Quantitative real-time PCR was carried out to detect the expression of HOXA13 and FN1 and the correlation between HOXA13 and FN1 in GC tissues. In vitro assays were conducted to investigate the role of HOXA13 and FN1 in the malignant phenotypes of GC cells and the function of HOXA13 in the activation of the FAK/Src axis in GC cells. Coimmunoprecipitation was performed to reveal the relationship between ITGA5, ITGB1 and FN1 in GC cells. A dual luciferase assay was performed to assess miR-449a-targeted regulation of HOXA13 expression.RESULTS:Quantitative real-time PCR verified that HOXA13 was elevated and positively correlated with FN1 in GC. In vitro and in vivo assays demonstrated that high expression of HOXA13 promoted GC progression, especially metastasis. Mechanistically, rescue experiments, chromatin immunoprecipitation and dual luciferase assays revealed that HOXA13 directly bound to the FN1 promoter region to enhance the activation of the FAK/Src axis, leading to GC cell proliferation and metastasis. Furthermore, the result of a dual luciferase assay suggested that HOXA13 was directly targeted by miR-449a.CONCLUSIONS:Our results show that HOXA13 is a positive regulator of the FAK/Src axis mediated by FN1 in GC and promotes GC progression. Thus, targeting HOXA13, together with FN1, may provide a novel prospective anticancer strategy.

BACKGROUND:Homeobox A10 (HOXA10) belongs to the HOX gene family, which plays an essential role in embryonic development and tumor progression. We previously demonstrated that HOXA10 was significantly upregulated in gastric cancer (GC) and promoted GC cell proliferation. This study was designed to investigate the role of HOXA10 in GC metastasis and explore the underlying mechanism.METHODS:Immunohistochemistry (IHC) was used to evaluate the expression of HOXA10 in GC. In vitro cell migration and invasion assays as well as in vivo mice metastatic models were utilized to investigate the effects of HOXA10 on GC metastasis. GSEA, western blot, qRT-PCR and confocal immunofluorescence experiments preliminarily analyzed the relationship between HOXA10 and EMT. ChIP-qPCR, dual-luciferase reporter (DLR), co-immunoprecipitation (CoIP), colorimetric m6A assay and mice lung metastasis rescue models were performed to explore the mechanism by which HOXA10 accelerated the EMT process in GC.RESULTS:In this study, we demonstrated HOXA10 was upregulated in GC patients and the difference was even more pronounced in patients with lymph node metastasis (LNM) than without. Functionally, HOXA10 promoted migration and invasion of GC cells in vitro and accelerated lung metastasis in vivo. EMT was an important mechanism responsible for HOXA10-involved metastasis. Mechanistically, we revealed HOXA10 enriched in the TGFB2 promoter region, promoted transcription, increased secretion, thus triggered the activation of TGFβ/Smad signaling with subsequent enhancement of Smad2/3 nuclear expression. Moreover, HOXA10 upregulation elevated m6A level and METTL3 expression in GC cells possible by regulating the TGFB2/Smad pathway. CoIP and ChIP-qPCR experiments demonstrated that Smad proteins played an important role in mediating METTL3 expression. Furthermore, we found HOXA10 and METTL3 were clinically relevant, and METTL3 was responsible for the HOXA10-mediated EMT process by performing rescue experiments with western blot and in vivo mice lung metastatic models.CONCLUSIONS:Our findings indicated the essential role of the HOXA10/TGFB2/Smad/METTL3 signaling axis in GC progression and metastasis.

Doctors entering surgical residency with different educational degrees and from different specialties is a unique feature of the Chinese medical system. The effect of this on the experience of surgical residents is not known. We retrospectively investigated whether residents' operative volumes were based on highest educational degree or postgraduate specialty. Using our operating data management system, a retrospective analysis of surgical resident operative experience at Shanghai General Hospital from 2012 to 2017 was conducted. The overall monthly average operative volume for surgical residents was 17.7 (12.6-26.5), but this decreased with each advanced degree of education from 26.0 (19.2-34.5) for those with a bachelor's degree only, to 19.5 (16.0-28.1) for a master's degree, to 15.9 (12.2-22.9) for those with a doctorate. Regarding specialty, residents in plastic surgery had the highest operative volume, and those in cardiothoracic surgery and neurosurgery had the lowest. At Shanghai General Hospital, the operative volumes of surgical residents differed according to their highest educational degree and postgraduate specialty. This analysis should be useful for the future planning of surgical residency programs in China.

目的 探讨同源盒基因A13 (HOXA13)表达水平对胃癌细胞5-氟尿嘧啶(5-FU)敏感性的影响及其可能的机制.方法 以HOXA13过表达与敲减稳转胃癌细胞株为研究工具,通过药物敏感实验检测HOXA13表达水平改变后,胃癌细胞对5-FU的敏感性有无改变.CCK-8、EdU实验检测HOXA13表达改变后对5-FU细胞增殖抑制作用的影响;流式细胞术检测HOXA13表达下调后对5-FU诱导胃癌细胞凋亡的影响;二代测序探讨HOXA13介导胃癌5-FU耐药的潜在机制.结果 HOXA13表达上调后,胃癌细胞5-FU的IC25和IC5o升高;下调HOXA13表达能够促进5-FU对胃癌细胞增殖的抑制作用,并促进5-FU诱导的细胞凋亡.ABC转运蛋白通路的激活可能是HOXA13引起胃癌细胞5-FU耐药的潜在机制.结论 HOXA13表达异常升高后能够削弱5-FU对胃癌细胞增殖的抑制作用,引起胃癌细胞对5-FU耐药,ABC转运蛋白可能作为重要下游效应分子参与该过程.

Background: Increasing evidence has found that the dysregulation of long non-coding RNAs (lncRNAs) may be important indicators in tumorigenesis. MYC-induced long non-coding RNA (MINCR) has been found to be related with some cancers, such as non-small cell lung cancer and gallbladder cancer. Besides, MINCR has potentially prognostic value for colon cancer (CC) patients' prognosis, yet its function and molecular mechanism in CC are not explored. Methods: qRT-PCR evaluated gene expression, and western blot detected protein level. In vitro and in vivo experiments were adopted to understand the biological role of MINCR in CC. TOP/FOP Flash assay was performed to measure the activity of Wnt/beta-catenin pathway. RNA pull down, luciferase reporter and RIP assays were utilized to analyze the relationship among genes. Immunohistochemistry and HE staining techniques were utilized to evaluate Ki67 staining in xenografts. Results: MINCR was up-regulated in CC cells. Knockdown of MINCR suppressed cell proliferation and migration. MINCR could up-regulate CTNNB1 via sequestering miR-708-5p, resulting in activated Wnt/beta-catenin pathway. The addition of LiCl treatment, miR-708-5p inhibitor or pcDNA3.1/CTNNB1 abolished the inhibitory impacts induced by MINCR silence in CC progression. Conclusion: MINCR sponges miR-708-5p to up-regulate CTNNB1 and activate Wnt/beta-catenin pathway, thus promoting the development CC. Targeting MINCR might shed new light on the therapeutic strategies of CC.

PURPOSE:HOXA13 is a transcription factor of the Homeobox (HOX) gene family, which is highly evolutionarily conserved. HOXA13 is upregulated and associated with oncogenic properties in some cancers. Here, we studied the potential mechanism of HOXA13-mediated proliferation and metastasis in gastric cancer (GC).METHODS:Quantitative real-time PCR, Western blot, and immunohistochemistry were used to detect HOXA13 expression levels in GC. In vitro and in vivo assays were performed to investigate the function of HOXA13 in GC cell proliferation, migration, and invasion. RNA-Seq transcriptome analysis was performed to study the underlying mechanism of HOXA13-mediated aggressiveness in GC.RESULTS:HOXA13 mRNA and protein expression levels were upregulated in GC tissues. According to Cell Counting Kit-8 and colony formation assays, we found that HOXA13 over-expression promoted proliferation. Flow cytometry analysis showed that HOXA13 overexpression or knockdown led to G1-S phase transition or G1 phase arrest, respectively. Western blot analysis results showed that HOXA13 overexpression increased cyclin D1 expression, while knockdown decreased its expression. Wound healing and transwell assay results demonstrated that HOXA13 overexpression promoted the migration and invasion of GC cells. Western blot analysis results also showed that HOXA13 overexpression upregulated N-cadherin and vimentin and downregulated E-cadherin, while HOXA13 knockdown led to the opposite results, indicating that HOXA13 might participate in epithelial to mesenchymal transition. These results were verified in vivo by tumor xenograft and metastasis assays. Mechanistically, using RNA-Seq transcriptome analysis, we found that Erk1/2 activation played an important role in HOXA13-induced GC progression.CONCLUSION:Our results show that HOXA13 plays an important role in GC development. HOXA13 overexpression promotes proliferation and metastasis partly via activation of Erk1/2 in GC. Thus, HOXA13, together with Erk1/2, may be promising targets for novel anticancer strategies.

目的:调查临床专业医学生法治意识的专业背景、了解法治意识薄弱区域,为今后制定具有针对性课程提供依据.方法:采用问卷调查方法,选择上海交通大学医学院2018—2019年度在读医学生从基本信息、基本法律知识、刑法、民法、法理等方面进行调查,并对所得数据进行统计学分析.结果:共发放问卷300份,总计回收有效问卷260份.结果显示86.3％的学生法治意识薄弱.42.3％的学生无观看法治节目或阅读相关图书、刊物的习惯,92.3％的学生没有使用法律解决纠纷的经验.结论:被研究对象法治意识普遍薄弱,获取知识渠道较少、学习知识主动性欠缺.其中性别可能成为一个危险因素.因此,目前亟须建立一套完善的具有针对性的医疗法律教育课程来改变现状.

目的:探讨PER2基因表达水平和结直肠癌发生发展的关系.方法:收集203例在上海市第一人民医院接受根治性肠切除术结直肠癌患者的标本,通过实时定量PCR和免疫组织化学技术检测PER2在肿瘤组织和邻近正常组织中的表达水平,并对PER2的表达与患者的病理资料和临床预后的相关性进行统计学分析.结果:PER2在结直肠患者肿瘤组织的表达较正常组织减少(P＜0.001).与PER2阳性患者相比,PER2阴性的结直肠癌患者有远处转移(P=0.026)、AJCC分期为Ⅳ期(P=0.011)的比例更高.结论:PER2基因在结直肠癌患者中存在低表达现象,其对于患者的AJCC分期评价以及了解患者有无远处转移有一定的参考价值.

Homeobox A10 (HOXA10) has been implicated critical for the promotion of carcinogenesis, but the underlying mechanism between HOXA10 and malignant gastric cancer (GC) phenotype remains elusive. In the present study, we analyzed and validated that HOXA10 and BCL2 expressions were elevated both at the mRNA and protein levels in GC tissues. Upregulated HOXA10 promoted GC cell proliferation with reduced apoptosis in vitro and accelerated GC tumor growth in vivo. Bioinformatics analysis and quantitative real-time polymerase chain reaction (qRT-PCR) experiment inferred that HOXA10 might upregulate the expression of BCL2. By performing western blot, chromatin immunoprecipitation and quantitative PCR (ChIP-qPCR), and rescue experiment, we found that HOXA10 might bind to BCL2 promoter region, induce its expression, and thus inhibit intrinsic apoptosis pathway. Moreover, higher expression of HOXA10 and BCL2 predicted poor overall survival (OS) in GC patients. In summary, our study indicated that HOXA10 was upregulated in GC, and that HOXA10 might promote cell proliferation by elevating BCL2 expression and inhibiting apoptosis.

Circulating tumor cells (CTCs) are defined as tumor in bloodstream or metastasis-derived cells.It can monitor the progress of metastatic diseases and may play an important role in determining tailored therapies of advanced cancer.The new blood marker technology may be the starting point of a clinical trial to study the pathogenesis of gastrointestinal tumors and the diagnosis and prognosis of gastrointestinal neoplasms and efficacy monitoring in the fulture.In the paper,role of CTCs in the diagnosis,prognosis of gastrointestinal neoplasms,monitoring efficacy and its prospect are reviewed.

Radiotherapy (RT) can be used as preoperative treatment to downstage initially unresectable locally rectal carcinoma, but radioresistance and recurrence remain significant problems. Retinoblastoma binding protein 6 (RBBP6) has been implicated in the regulation of cell cycle, apoptosis and chemoresistance both in vitro and in vivo. The present study investigated whether the inhibition of RBBP6 expression would improve radiosensitivity in human colorectal cancer cells. After SW620 and HT29 cells were exposed to radiation, the levels of RBBP6 mRNA and protein increased over time in both cells. Moreover, a significant reduction in clonogenic survival and a decrease in cell viability in parallel with an obvious increase in cell apoptosis were demonstrated in irradiated RBBP6-knockdown cells. Transfection with RBBP6 shRNA improved the levels of G2-M phase arrest, which blocked the cells in a more radiosensitive period of the cell cycle. These observations indicated that cell cycle and apoptosis mechanisms may be connected with tumor cell survival following radiotherapy. In vivo, the tumor growth rate of nude mice in the RBBP6-knockdown group was significantly slower than that in other groups. These results indicated that RBBP6 overexpression could resist colorectal cancer cells against radiation by regulating cell cycle and apoptosis pathways, and inhibition of RBBP6 could enhance radiosensitivity of human colorectal cancer.

Objective To investigate the effect of homeobox gene A10 (HOXA10) with changed expression level on xenograft tumor formation of gastric cancer cell and the possible mechanism.Methods Bioinformatics analysis was made to the expression of HOXA10 in gastric cancer in The Cancer Genome Atlas website (TCGA) database;stable HOXA10 knockdown gastric cancer cell line BGC-823-sh-HOXA10 was constructed and performed in the xenograft tumor formation assay;the expression of apoptosis related protein Bcl-xL was detected by western blot.Results The analysis of TCGA database showed that the expression of HOXA 10 in gastric cancer was up-regulated;HOXA10 knockdown impaired the ability of xenograft tumor formation in BGC-823 cell line and the expression of Bcl-xL was down-regulated.Conclusions HOXA10 was upregulated in gastric cancer;HOXA10 knockdown may inhibit the ability of xenograft tumor formation in BGC-823 cell line and the down-regulation of antiapoptosis protein Bcl-xL after HOXA10 knockdown may be the possible mechanism.

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide, and immune checkpoint blockade therapy provides an opportunity for improving the outcome of CRC patients. Recent studies suggest that programmed death ligand-1 (PD-L1) is only expressed in 12% of CRCs. Here, we demonstrate that PD-L2 is expressed in approximately 40% CRCs, and its expression independently associates with poor survival of CRC patients. By detection of PD-L2 expression by immunofluorescence in 124 CRC cases with 10-y survival data, we found significant association between PD-L2 overexpression in cancer cells and worse overall survival (46.3 vs 69.1 mo; p = 0.0004). The association remained significant in multivariate COX regression analysis (hazard ratio = 2.778, 95% confidence interval [CI] = 1.668–4.627; p < 0.0001). In the validation CRC data set, significant association between PD-L2 overexpression and poor survival was supported by the univariate analysis (27.1 vs. 88.9 mo; p = 0.0002) and multivariate model (hazard ratio = 7.09, 95%CI 1.78–28.16; p = 0.005). Western Blot revealed strong induction of PD-L2 expression by interferon-γ (IFNγ) in CRC cells, and the mRNA levels of both genes were significantly correlated in CRC tissue samples. Suppression of glycosylation with tunicamycin caused a shift in molecular weight and significant decrease in the expression of PD-L2 protein. In conclusion, PD-L2 overexpression in CRC cells, under the regulation by IFNγ and glycosylation, associates with poor survival of patients with colorectal cancer. These findings highlight PD-L2 as a promising therapeutic target in CRC and suggest potential routes to control PD-L2 expression in CRC cells.

We previously discovered that Ras association domain family member 6 (RASSF6) was downregulated and predicted poor prognosis in GC patients. However, the mechanisms of the down regulation of RASSF6 in GC remained unclear. Increasing evidence indicates that dysregulation of microRNAs promotes the progression of cancer through the repression of tumour suppressors. Here, we identified miR-181a-5p as a novel regulator of RASSF6 in GC. Functionally, ectopic expression or silencing of miR-181a-5p, respectively, promoted or inhibited GC cell proliferation, colony formation and cell cycle transition, as well as enhanced or prevented the invasion, metastasis of GC cells and epithelial to mesenchymal transition of GC cells in vitro and in vivo. Molecularly, miR-181a-5p functioned as an onco-miRNA by activating the RASSF6-regulated MAKP pathway. Overexpression or silencing of RASSF6 could partially reverse the effects of the overexpression or repression of miR-181a-5p on GC progress caused by activation of the MAKP pathway in vitro and in vivo. Clinically, high miR-181a-5p expression predicted poor survival in GC patients, especially combined with low RASSF6 expression. Collectively, we identified miR-181a-5p as an onco-miRNA, which acts by directly repressing RASSF6 in GC.

Homeobox gene is an important gene family of developmental regulatory in the body.It is highly conserved in the evolutionary process.It is widely found in nervous,digestive,respiratory,circulatory,blood and genitourinary system,involved in rcgulating the growth and development of individuals,cells' proliferation,differentiation,apoptosis and other processes.The present studies show that the abnormal expressions of homeobox genes are closely related to the occurrence,development and prognosis of human multiple malignancies.In this paper,the research progress and prospect of the relationship between homeobox genes' family and development of digestive system tumors are reviewed.

Objective To investigate the relation between the expression of KIF14 and the prognosis of gastroenteric tumor.Methods We enrolled 112 patients who were confirmed with gastroenteric tumor by surgery and postoperative pathology in the General Hospital of Ningxia Medical University and the First People′s Hospital Affiliated to Shanghai Jiaotong University from January 2008 to December 2010.The clinical features of patients were collected; follow -up was conducted by further consultation, telephone and letters, with pathological diagnosis as the starting point and tumor relapse and metastasis and death as the end points; the follow-up ended on March 31, 2015.The focus of gastroenteric tumor and para-carcinoma tissue were excised during surgery; the relative quantity ( RQ) of KIF14 mRNA was detected by RT-PCR, and the expression results of&nbsp;KIF14 was detected by immunohistochemistry; immunohistochemical results were confirmed by two pathological doctors separately.Results We observed that the expression of KIF14 mRNA was high in 72 samples of gastrointestinal cancerous tissues, and RQ was 58.00 (37.00, 138.00).However, KIF14 mRNA expression was low in 40 samples of the patients, and RQ was 0.68 (0.46, 0.79).The positive reactants of KIF14 protein in gastrointestinal cancer tissues were localized in the cell nucleus or cytoplasm of cancer cells, taking on the color of claybank and the shape of homogeneity and granules.The expression of KIF14 mRNA was weak or negative in para-carcinoma tissues.The KIF14 positive rate was 61.6% (69/112), more than that of para-carcinoma tissues which was 7.1% (8/112), and the difference was significant (χ2 =76.557, P<0.001).The KIF14 mRNA RQ was not statistically different by age, gender, tumor location, tumor size and differentiation degree ( P >0.05).KIF14 mRNA RQ was significantly by depth of infiltration, clinical stage, presence of lymph node metastasis and the distant metastasis (P<0.05).The 5-year overall survival (OS) rate of the 112 gastrointestinal cancer patients was 48.2%(54/112).The median survival time of patients with KIF14 mRNA high expression and low expression was 52 and 67 months respectively, and the two kinds of patients were significantly different in survivorship curve (χ2 =8.210, P=0.004) .The 5-year DFS rate was 38.6% ( 39/101 ) among 101 patients without metastasis after surgery, and the median survival time of patients with KIF14 mRNA high expression and low expression was 41 and 62 months respectively; the two kinds of patients were significantly different in survivolship curve (χ2 =17.281, P<0.001).Patients with high KIF14 mRNA expression were higher than patients with low KIF14 mRNA expression in the risk of relapse and metastasis 〔AR=6.9, 95%CI (2.8, 16.8), P<0.001〕.Multivariate Cox regression analysis showed that depth of infiltration, lymphatic metastasis, distant metastisis and KIF14 mRNA were independent influencing factors for death within 5 years, and depth of infiltration, lymphatic metastasis and KIF14 mRNA were independent influencing factors for the metastasis and recurrence within 5 years (P<0.05).Conclusion Gastrointestinal cancer tissues have higher expression of KIF14 mRNA and protein, and participate in the occurrence, progress, invasion, metastasis and other biological behaviors of gastroenteric tumor.KIF14 mRNA can be used as one of molecular biological markers for the prognosis of patients with gastrointestinal cancer who have received radical resection.

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, and its prevalence is rapidly increasing in Han Chinese individuals. Several studies have demonstrated that polymorphisms of the PARVB gene may play crucial roles in the development of NAFLD. Therefore, the present study was designed to investigate the association of rs5764455 and rs6006473 polymorphisms in PARVB with the Han Chinese population's susceptibility to NAFLD. Methods: A total of 384 cases of NAFLD patients and 384 healthy controls were enrolled in this study. Their clinical information and serum biochemical indexes were analyzed. A sample (5 ml) of fasting venous blood was taken from each subject for DNA extraction, after which SNP probes were customized, and real-time PCR was used to detect SNP in the PARVB gene. Results: Patients with genotype AA of rs5764455 SNP locus in PARVB gene had a higher incidence of NAFLD than patients with genotypes AG and GG (62.1% vs. 50.3% and 46.9%, respectively, p-values = 0.034). Patients with genotype TT of rs6006473 SNP had a higher incidence of NAFLD than patients with genotypes CT and CC (56.9% vs. 49.9% and 42.0%, respectively, p-values = 0.017). The ORs of the A allele and M genotype of rs5764455 for NAFLD were 130 and 1.62, respectively; those of the T allele and TT genotype of rs6006473 for NAFLD were 134 and 1.35, respectively. Further analysis revealed that patients with genotype AA of rs5764455 and genotype of rs6006473 had higher levels of plasma triglyceride, LDL-C, ALT and AST (p-values <0.05). Likewise, patients with genotype AA of rs5764455 had a higher incidence of moderate to severe NAFLD than patients with genotypes AG and GG (62.7% vs. 44.3% and 43.0%, respectively, p-values = 0.026). Patients with genotype TT of rs6006473 had a higher incidence of moderate to severe NAFLD than patients with genotypes CT and CC (59.6% vs. 46.6% and 30.9%, respectively, p-values = 0.001). Conclusions: Our study found polymorphisms of rs5764455 and rs6006473 in PARVB gene in the Han Chinese population, and these polymorphisms were associated with the occurrence and progression of NAFLD. (C) 2015 Elsevier B.V. All rights reserved.

BACKGROUND:HOXA1 is a member of the Homeobox gene family, which encodes a group of highly conserved transcription factors that are important in embryonic development. However, it has been reported that HOXA1 exhibits oncogenic properties in many malignancies. This study focused on the expression and clinical significance of HOXA1 in gastric cancer (GC).METHODS:To assess the mRNA and protein expression of HOXA1 and cyclin D1 in GC tissues, we utilized qRT-PCR and western blotting, respectively. The effects of HOXA1 on GC cell proliferation, migration, and invasion, as well as xenograft tumor formation and the cell cycle were investigated in our established stable HOXA1 knockdown GC cell lines. The protein expression of HOXA1 and cyclin D1 was examined by immunohistochemistry using GC tissue microarrays (TMA) to analyze their relationship on a histological level. The Kaplan-Meier method and cox proportional hazards model were used to analyze the relationship of HOXA1 and cyclin D1 expression with GC clinical outcomes.RESULTS:HOXA1 mRNA and protein expression were upregulated in GC tissues. Knockdown of HOXA1 in GC cells not only inhibited cell proliferation, migration, and invasion in vitro but also suppressed xenograft tumor formation in vivo. Moreover, HOXA1 knockdown induced changes in the cell cycle, and HOXA1 knockdown cells were arrested at the G1 phase, the number of cells in S phase was reduced, and the expression of cyclin D1 was decreased. In GC tissues, high cyclin D1 mRNA and protein expression were detected, and a significant correlation was found between the expression of HOXA1 and cyclin D1. Survival analysis indicated that HOXA1 and cyclin D1 expression were significantly associated with disease-free survival (DFS) and overall survival (OS). Interestingly, patients with tumors that were positive for HOXA1 and cyclin D1 expression showed worse prognosis. Multivariate analysis confirmed that the combination of HOXA1 and cyclin D1 was an independent prognostic indicator for OS and DFS.CONCLUSION:Our data show that HOXA1 plays a crucial role in GC development and clinical prognosis. HOXA1, alone or combination with cyclin D1, may serve as a novel prognostic biomarker for GC.