Silencing of KIF2C enhances the sensitivity of hepatocellular carcinoma cells to cisplatin through regulating the PI3K/AKT/MAPK signaling pathway.

In the treatment of unresectable advanced hepatocellular carcinoma (HCC), cisplatin is administered transhepatic arterially for local treatment, but the clinical application of cisplatin drugs is frequently hindered by the emergence of drug resistance. Kinesin family member 2C( KIF2C ) has been shown as oncogene in a variety of tumors. Nevertheless, its effect on cisplatin sensitivity has yet to be ascertained. Herein, we aim to investigate the impact of the KIF2C gene on cisplatin sensitivity within HCC and the plausible underlying molecular mechanism. We examined the expression level of the KIF2C gene in HCC cells by real-time quantitative reverse transcription PCR and Western blot analysis, and analyzed bioinformatically by The Gene Expression Omnibus database and The Cancer Genome Atlas database. The KIF2C gene was silenced using the small interfering RNA technology, and its effect on cisplatin drug sensitivity in HCC cells was evaluated by flow cytometry, cell proliferation, cell migration, and invasion assays. Our results indicated that KIF2C was highly expressed in HCC cells. KIF2C silencing inhibits HCC cell proliferation, migration and invasion, promotes apoptosis, and keeps the cell cycle in G2 phase. In addition, KIF2C silencing enhanced the sensitivity of HCC cells to cisplatin. KIF2C silencing down-regulates the expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and mitogen-activated protein kinase 3 (MAPK3) proteins. In conclusion, KIF2C silencing amplifies the sensitivity of HCC cells to cisplatin by regulating the PI3K/AKT/MAPK signaling pathway. Consequently, targeting KIF2C shows great application potential as a strategy for enhancing the effectiveness of HCC treatment.

Outer dynein arm docking complex subunit 2 polymorphism rs7893462 modulates hepatocellular carcinoma susceptibility and can serve as an overall survival biomarker for hepatitis B virus-related hepatocellular carcinoma after hepatectomy: a cohort study with a long-term follow-up.

BACKGROUND: Genetic variants of outer dynein arm docking complex subunit 2 (ODAD2) have been reported to be closely associated with primary ciliary dyskinesia and colorectal cancer in previous studies, but the association of genetic variants of ODAD2 with hepatocellular carcinoma (HCC) has not been reported. METHODS: We enrolled 80 healthy subjects and 468 Guangxi hepatitis B virus (HBV)-related HCC patients in this study. A case-control study method was used to explore the association of different ODAD2-rs7893462 genotypes with hepatocarcinogenesis. A comprehensive survival analysis was used to explore the association of rs7893462 with the prognosis of HBV-related HCC in Guangxi. RESULTS: Through a case-control study, we observed that patients carrying the G allele of rs7893462 had a markedly increased susceptibility to hepatocarcinogenesis (odds ratio = 1.712, 95% confidence interval = 1.032-2.839, P = 0.037). We found that there were significant prognosis differences among three different genotypes of rs7893462. Nomogram analysis suggested that the contribution of rs7893462 polymorphisms to the prognosis of HBV-related HCC was second only to the BCLC stage. Stratified survival analysis suggested that the AG genotype of rs7893462 was an independent prognostic risk factor for HBV-related HCC. Joint effect survival analysis also observed that the AG genotype of rs7893462 combined with clinical parameters could significantly identify HBV-related HCC patients with different prognostic outcomes more accurately, and the AG genotype was also observed to be independent of clinical factors in HBV-related HCC survival. CONCLUSION: The ODAD2-rs7893462 polymorphisms can be used as an independent prognostic indicator of HBV-related HCC overall survival and are significantly associated with susceptibility to hepatocarcinogenesis.

Gender disparity in hepatocellular carcinoma recurrence after curative hepatectomy.

INTRODUCTION AND OBJECTIVES: Whether there is gender disparity in the recurrence of hepatocellular carcinoma (HCC) has been not fully addressed. This study aimed to investigate the impact of gender on HCC recurrence following curative hepatectomy. PATIENTS AND METHODS: This retrospective cohort study included 1087 patients with HCC (917 males, 170 females) who underwent curative hepatectomy. Cox regression models were constructed to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the risk parameters associated with HCC recurrence. In the sensitivity analysis, subgroup analysis, and propensity score matching (PSM) analysis were used. Logistic regression models were used to assess the odds ratio (OR) and 95% CI of the risk parameters related to early and late recurrence. RESULTS: Male patients showed significantly higher risk for HCC recurrence than females, in both multivariate Cox regression analysis (HR [95% CI] = 1.480 [1.084-2.020], P = 0.014) and PSM analysis (HR [95% CI] = 1.589 [1.093-2.312], P = 0.015). Higher risk of HCC recurrence was again found in males in the subgroup analysis, but the effect of male versus female gender on HCC recurrence did not depend on any selected subgroups (all P for interaction > 0.05). Gender was an independent risk factor for early recurrence (OR [95% CI] = 1.864 [1.215-2.936], P = 0.006), but not for late recurrence. CONCLUSIONS: There is gender disparity in the recurrence of patients with HCC after curative hepatectomy: males had a higher risk for HCC recurrence than females.

Effect of timing of surgical resection of primary hepatocellular carcinoma on survival outcomes in elderly patients and prediction of clinical models.

BACKGROUND: The effect of time delay from diagnosis to surgery on the prognosis of elderly patients with liver cancer is not well known. We investigated the effect of surgical timing on the prognosis of elderly hepatocellular carcinoma patients undergoing surgical resection and constructed a Nomogram model to predict the overall survival of patients. METHODS: A retrospective analysis was performed on elderly patients with primary liver cancer after hepatectomy from 2012 to 2018. The effect of surgical timing on the prognosis of elderly patients with liver cancer was analyzed using the cut-off times of 18 days, 30 days, and 60 days. Cox was used to analyze the independent influencing factors of overall survival in patients, and a prognostic model was constructed. RESULTS: A total of 232 elderly hepatocellular carcinoma patients who underwent hepatectomy were enrolled in this study. The cut-off times of 18, 30, and 60 days were used. The duration of surgery had no significant effect on overall survival. Body Mass Index, Child-Pugh classification, Tumor size Max, and Length of stay were independent influencing factors for overall survival in the elderly Liver cancer patients after surgery. These factors combined with Liver cirrhosis and Venous tumor emboli were incorporated into a Nomogram. The nomogram was validated using the clinical data of the study patients, and exhibited better prediction for 1-year, 3-year, and 5-year overall survival. CONCLUSIONS: We demonstrated that the operative time has no significant effect on delayed operation in the elderly patients with hepatocellular carcinoma, and a moderate delay may benefit some patients. The constructed Nomogram model is a good predictor of overall survival in elderly patients with hepatectomy.

ACSL4 is a predictive biomarker of sorafenib sensitivity in hepatocellular carcinoma.

Sorafenib is the first-line treatment of advanced hepatocellular carcinoma (HCC). However, there is a lack of validated biomarkers to predict sorafenib sensitivity. In this study we investigated the role of ACSL4, a positive-activating enzyme of ferroptosis, in sorafenib-induced cell death and HCC patient outcome. We showed that ACSL4 protein expression was negatively associated with IC50 values of sorafenib in a panel of HCC cell lines (R = -0.952, P < 0.001). Knockdown of ACSL4 expression by specific siRNA/sgRNA significantly attenuated sorafenib-induced lipid peroxidation and ferroptosis in Huh7 cells, and also rescued sorafenib-induced inhibition of xenograft tumor growth in vivo. We selected 29 HCC patients with surgery as primary treatment and sorafenib as postoperative adjunct therapy from a hospital-based cohort. A high proportion (66.7%) of HCC patients who had complete or partial responses to sorafenib treatment (according to the revised RECIST guideline) had higher ACSL4 expression in the pretreated HCC tissues, compared with those who had stable or progressed tumor growth (23.5%, P = 0.029). Since ACSL4 expression was independent of sorafenib treatment, it could serve as a useful predictive biomarker. Taken together, this study demonstrates that ACSL4 is essential for sorafenib-induced ferroptosis and useful for predicting sorafenib sensitivity in HCC. This study may have important translational impacts in precise treatment of HCC.

Type 2 sclerotic Modic change affect fusion result in patients undergoing PLIF with pedicle screw instrumentation: a retrospective study.

BACKGROUND: Bony fusion rate was significantly lower in patients with type 3 Modic change than patients with normal endplates. It is not known whether there are relevant differences in fusion efficiency among patients with type 2 sclerotic Modic change or non-sclerotic Modic change, or no Modic change. METHODS: A retrospective study contained 196 lumbar segments in 123 subjects undergoing posterior lumbar interbody fusion (PLIF) with pedicle screw instrumentation (PSI) to assess the effect of type 2 sclerotic Modic change on fusion efficiency. These endplates were allocated into groups A, B, and C, according to their Modic changes. Group A had endplates with type 2 Modic change and endplate sclerosis. Group B had type 2 Modic change without endplate sclerosis. Group C had neither Modic change nor endplate sclerosis. The presence of Modic change was determined by magnetic resonance imaging (MRI). Endplate sclerosis in type 2 Modic change was detected by computed tomography (CT) before the operation. We collected CT data 3 months to more than 24 months after operation in patients to assess bony fusion. RESULTS: Incidences of bony fusion were 58.8% in group A, 95.0% in group B, 94.3% in group C. The bony fusion rate was significantly lower in group A than in either group B or C. There was no significant difference between groups B and C. Thus, endplates with type 2 sclerotic Modic change had a lower fusion rate in patients undergoing PLIF with PSI. CONCLUSION: Type 2 sclerotic Modic change could be an important factor that affects solid bony fusion in patients undergoing PLIF with PSI. CT may help diagnose endplate sclerosis in patients with type 2 change and inform the choice of the best site for spinal fusion.

Oncogene PLCE1 may be a diagnostic biomarker and prognostic biomarker by influencing cell cycle, proliferation, migration, and invasion ability in hepatocellular carcinoma cell lines.

Hepatocellular carcinoma (HCC) is a lethal malignancy worldwide. HCC has traits of late diagnosis and high recurrence. This study explored potential diagnosis and prognosis significance of phospholipase C epsilon 1 (PLCE1) in HCC. The messenger RNA (mRNA) levels and diagnostic value of PLCE1 were determined by real-time polymerase chain reaction and online databases GEPIA, oncomine, and GSE14520 data set. Survival analysis used the Kaplan-Meier Plotter website. Cell cycle, proliferation, migration, and invasion assays were performed with downregulated PLCE1 expression in HCC-M and HepG2 cell lines. PLCE1 was differentially expressed and highly expressed in tumors and had low expression in nontumor tissues (all p < .05). The diagnostic value of PLCE1 was validated with the datasets (all p < .01, all areas under curves > 0.7). PLCE1 mRNA expression was associated with the overall and relapse-free survival (both p < .05). Functional experiments indicated that downregulation of PLCE1 expression led to increased G1 stage in cell cycle and decreased cell proliferation, migration, and invasion compared with a negative control group (all p ≤ .05). The oncogene PLCE1 was differentially expressed in HCC and non-HCC tissues. It is a candidate for diagnosis and serves as prognosis biomarker. PLCE1 influenced survival by affecting the cell cycle, proliferation, migration, and invasion ability.

Prognostic value of Glypican family genes in early-stage pancreatic ductal adenocarcinoma after pancreaticoduodenectomy and possible mechanisms.

BACKGROUND: This study explored the prognostic significance of Glypican (GPC) family genes in patients with pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). METHODS: A total of 112 PDAC patients from TCGA and 48 patients from GEO were included in the analysis. The relationship between overall survival and the expression of GPC family genes as well as basic clinical characteristics was analyzed using the Kaplan-Meier method with the log-rank test. Joint effects survival analysis was performed to further examine the relationship between GPC genes and prognosis. A prognosis nomogram was established based on clinical characteristics and prognosis-related genes. Prognosis-related genes were investigated by genome-wide co-expression analysis and gene set enrichment analysis (GSEA) was carried out to identify potential mechanisms of these genes affecting prognosis. RESULTS: In TCGA database, high expression of GPC2, GPC3, and GPC5 was significantly associated with favorable survival (log-rank P = 0.031, 0.021, and 0.028, respectively; adjusted P value = 0.005, 0.022, and 0.020, respectively), and joint effects analysis of these genes was effective for prognosis prediction. The prognosis nomogram was applied to predict the survival probability using the total scores calculated. Genome-wide co-expression and GSEA analysis suggested that the GPC2 may affect prognosis through sequence-specific DNA binding, protein transport, cell differentiation and oncogenic signatures (KRAS, RAF, STK33, and VEGFA). GPC3 may be related to cell adhesion, angiogenesis, inflammatory response, signaling pathways like Ras, Rap1, PI3K-Akt, chemokine, GPCR, and signatures like cyclin D1, p53, PTEN. GPC5 may be involved in transcription factor complex, TFRC1, oncogenic signatures (HOXA9 and BMI1), gene methylation, phospholipid metabolic process, glycerophospholipid metabolism, cell cycle, and EGFR pathway. CONCLUSION: GPC2, GPC3, and GPC5 expression may serve as prognostic indicators in PDAC, and combination of these genes showed a higher efficiency for prognosis prediction.

Diagnostic and prognostic significance of mRNA expressions of apolipoprotein A and C family genes in hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is among the most common and lethal malignancies worldwide. Apolipoproteins (APOs) have been reported increasingly for their relationships with tumors. We aim at exploring the potential relationships of apolipoprotein A (APOA) and apolipoprotein C (APOC) family members with HCC. METHODS: A data set, containing 212 hepatitis B virus-related HCC patients, was used for analysis. The diagnostic and prognostic ability of APOA and APOC family genes was figured out. Risk score models and nomograms were developed for the HCC prognosis prediction. Moreover, molecular mechanism exploration were identified biological processes and metabolic pathways of these genes involved in. Validation analysis was carried out using online website. RESULTS: APOA1, APOC1, APOC3, and APOC4 showed robust diagnosis significance (all P < 0.05). APOA4, APOC3, and APOC4 were associated with the overall survival (OS) while APOA4 and APOC4 were linked to recurrence-free survival (RFS, all P ≤ 0.05). Risk score models and nomograms had the advantage of predicting OS and RFS for HCC. Molecular mechanism exploration indicated that these genes were involved in the steroid metabolic process, the PPAR signaling pathway, and fatty acid metabolism. Besides that, validation analysis revealed that APOC1 and APOC4 had an association with OS; and APOC3 was associated with OS and RFS (all P ≤ 0.05). CONCLUSIONS: APOA1, APOC1, APOC3, and APOC4 are likely to be potential diagnostic biomarkers and APOC3 and APOC4 are likely to be potential prognostic biomarkers for hepatitis B virus-related HCC. They may be involved in the steroid metabolic process, PPAR signaling pathway, and fatty acid metabolism.

Identification of Potential Prognostic Long Non-Coding RNA Biomarkers for Predicting Survival in Patients with Hepatocellular Carcinoma.

BACKGROUND/AIMS: The aim of the current study was to identify potential prognostic long non-coding RNA (lncRNA) biomarkers for predicting survival in patients with hepatocellular carcinoma (HCC) using The Cancer Genome Atlas (TCGA) dataset and bioinformatics analysis. METHODS: RNA sequencing and clinical data of HCC patients from TCGA were used for prognostic association assessment by univariate Cox analysis. A prognostic signature was built using stepwise multivariable Cox analysis, and a comprehensive analysis was performed to evaluate its prognostic value. The prognostic signature was further evaluated by functional assessment and bioinformatics analysis. RESULTS: Thirteen differentially expressed lncRNAs (DELs) were identified and used to construct a single prognostic signature. Patients with high risk scores showed a significantly increased risk of death (adjusted P < 0.0001, adjusted hazard ratio = 3.522, 95% confidence interval = 2.307-5.376). In the time-dependent receiver operating characteristic analysis, the prognostic signature performed well for HCC survival prediction with an area under curve of 0.809, 0.782 and 0.79 for 1-, 3- and 5-year survival, respectively. Comprehensive survival analysis of the 13-DEL prognostic signature suggested that it serves as an independent factor in HCC, showing a better performance for prognosis prediction than traditional clinical indicators. Functional assessment and bioinformatics analysis suggested that the prognostic signature was associated with the cell cycle and peroxisome proliferator-activated receptor signaling pathway. CONCLUSIONS: The novel lncRNA expression signature identified in the present study may be a potential biomarker for predicting the prognosis of HCC patients.

Distinct Diagnostic and Prognostic Values of Kinesin Family Member Genes Expression in Patients with Breast Cancer.

BACKGROUND This study investigated the diagnostic and prognostic values of kinesin superfamily proteins (KIFs) in breast cancer (BC) patients. MATERIAL AND METHODS All data were obtained from the Cancer Genome Atlas. DESeq was run to test for differentially expressed KIF genes. Patients were divided into high- and low-expression groups according to the median expression values of each KIF genes. Survival data were calculated using the Cox proportional hazard model. Comprehensive survival analysis was performed to evaluate the prognostic value of the prognostic signature. Gene set enrichment analysis (GSEA) was conducted to identify associated gene ontology and KEGG pathways. RESULTS Bioinformatics analysis showed that all KIF genes were significantly enriched during DNA replication and the cell cycle, and co-expressed with each other. Thirteen KIF genes were differentially expressed in cancer and adjacent tissues, and high levels of KIF15, KIF20A, KIF23, KIF2C and KIF4A genes were significantly correlated with poor overall survival (OS). GSEA showed that BC patients with high expression of KIF15, KIF20A, KIF23, KIF2C and KIF4A were enriched in the cell cycle process, P53 regulation pathway and mismatch repair. Combinations of low expression of KIF15, KIF20A, KIF23, KIF2C and KIF4A were more highly correlated with favorable OS. Nomograms showed that the KIF4A risk score provided the maximum number of risk points (range 0-100), whereas other genes made a lower contribution. CONCLUSIONS We conclude that 13 KIF genes are differentially expressed in BC tumor tissues, and KIF15, KIF20A, KIF23, KIF2C and KIF4A are associated with prognostic factors in BC.

Genome-Wide Association Study of MKI67 Expression and its Clinical Implications in HBV-Related Hepatocellular Carcinoma in Southern China.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a common malignant tumor with a high rate of recurrence. Immunohistochemical analysis of the marker of proliferation Ki-67 (MKI67) is used to assess proliferation activity of HCC The regulation of MKI67 expression remains unclear in HCC This study aims to explore the association between MKI67 expression and gene variants. METHODS: A total of 195 hepatitis B virus (HBV)-related HCC patients were genotyped using Illumina HumanExome BeadChip-12-1_A (242,901 markers). An independent cohort (97 subjects) validated the association of polymorphism determinants and candidate genes with MKI67 expression. The relationships between MKI67 with p53 and variants of candidate genes in the clinical outcomes of HCC patients were analyzed. RESULTS: We found that MKI67 combined with p53 was associated with a 3-year recurrence-free survival and five variants near TTN and CCDC8 were associated with MKI67 expression. TTN harboring rs2288563-TT and rs2562832-AA+CA indicated a favorable outcome for HCC patients. CONCLUSION: Variants near TTN and CCDC8 were associated with MKI67 expression, and rs2288563 and rs2562832 in TTN are potential biomarkers for the prediction of clinical outcomes in HBV-related HCC patients.

Increased expression of microRNA-31-5p inhibits cell proliferation, migration, and invasion via regulating Sp1 transcription factor in HepG2 hepatocellular carcinoma cell line.

Accumulating evidence has suggested that microRNA-31-5p (miR-31-5p) is dysfunctional in hepatocellular carcinoma (HCC). However, the molecular mechanism of HCC remains unclear. In this study, we investigated the role of miR-31-5p in tumor formation and development of HCC. The expression of miR-31-5p was detected in HCC tissues, corresponding adjacent tissues, normal liver tissues, and HCC cell lines. miR-31-5p mimics and an inhibitor were transfected into HepG2 cells to assess the effects of miR-31-5p on cell proliferation, apoptosis, cell cycle, migration, and invasion assays. Western blotting was used to detect the expression of Sp1 transcription factor (SP1), cyclin D1, and survivin in transfected HCC cells and control cells. The expression of miR-31-5p was significantly decreased in HCC cells and HCC tissues. Overexpression of miR-31-5p inhibited HCC cell growth, migration, and invasion. Overexpression of miR-31-5p reduced the expression of SP1 and cyclin D1, and knockdown of SP1 decreased cyclin D1 expression. The dual luciferase assay showed that miR-31-5p directly targeted SP1 in HepG2. Together, the results suggested that miR-31-5p acted as a tumor suppressor to regulate SP1, and that miR-31-5p could be used as a therapeutic target for the treatment of HCC.

ATXN7 Gene Variants and Expression Predict Post-Operative Clinical Outcomes in Hepatitis B Virus-Related Hepatocellular Carcinoma.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a lethal disease with nearly equal morbidity and mortality. Thus, the discovery and application of more useful predictive biomarkers for improving therapeutic effects and prediction of clinical outcomes is of crucial significance. METHODS: A total of 475 HBV-related HCC patients were enrolled. Ataxin 7 (ATXN7) single nucleotide polymorphisms (SNPs) were genotyped by Sanger DNA sequencing after PCR amplification. The associations between ATXN7 SNPs and mRNA expression with the prognosis of HBV-related HCC were analyzed. RESULTS: In all, rs3774729 was significantly associated with overall survival (OS) of HBV-related HCC (P = 0.013, HR = 0.66, 95% CI: 0.48-0.94). And patients with the AA genotype and a high level of serum alpha fetoprotein (AFP) had significantly worse OS when compared to patients with AG/GG genotypes and a low level of AFP (adjusted P = 0.007, adjusted HR = 1.83, 95% CI = 1.18-2.82). Furthermore, low expression of ATXN7 was significantly associated with poor recurrence-free survival (RFS) and OS (P = 0.007, HR = 2.38, 95% CI = 1.27-4.45 and P = 0.025, HR = 1.75, 95% CI = 1.18-2.62). CONCLUSION: ATXN7 may be a potential predictor of post-operative prognosis of HBV-related HCC.

XRCC1 rs25487 genetic variant and TP53 mutation at codon 249 predict clinical outcomes of hepatitis B virus-related hepatocellular carcinoma after hepatectomy: A cohort study for 10 years' follow up.

AIM: To investigate the effects of rs25487 (the DNA repair gene: x-ray repair complementing defective repair in Chinese hamster cells 1 [XRCC1]) and codon 249 mutation (TP53 gene) on clinical outcomes of post-hepatectomy hepatitis B virus (HBV)-related HCC. METHODS: The XRCC1 rs25487 polymorphism and TP53 mutation at codon 249 of 485 hepatitis B surface antigen positive patients subjected to hepatectomy were genotyped via direct sequencing. SPSS software version 16.0 (SPSS, Chicago, IL, USA) was used to calculate survival of HCC patients according to primary end-points. RESULTS: The presence of at least one A allele (AA/AG) of rs25487 was associated with unfavorable prognosis (P = 0.005). Moreover, A allele (AA/AG) carriers were significantly associated with high risk of vascular invasion (P = 0.025) and regional invasion (P = 0.005). Differences were not significant between mutant and wild-type TP53 cases with overall survival (adjusted P = 0.400). Among the 485 participants, patients (n = 73) carrying both the A allele (AA/AG) of rs25487 and 249Ser TP53 mutation displayed decreased overall survival, compared with patients (n = 184) with the GG genotype of rs25487 and wild-type codon 249 (adjusted P = 0.007). CONCLUSION: Polymorphisms of rs25487 may play a potential role in survival of HBV-related hepatocellular carcinoma patients following hepatectomy. While mutation at codon 249 of TP53 is not associated with HBV-related HCC survival in this study.

Association of variants in 21q22 with ankylosing spondylitis in the Chinese Guangxi Zhuang population.

Genome-wide association study has reported a number of genes as being associated with ankylosing spondylitis (AS) in Caucasian European populations and Chinese Han population. The aim of the study was to investigate whether single nucleotide polymorphisms (SNPs) covering the 21q22 region are associated with AS in the Chinese Guangxi Zhuang population. A case-control study was performed in unrelated patients with AS (n = 315) and age-, sex-, and ethnicity-matched controls (n = 630) from Guangxi Zhuang ethnic group. All patients met the modified New York criteria for AS. TaqMan genotyping assay was used to genotype cases and controls for 17 tag SNPs covering 21q22. After multiple-testing correction, significant association with AS was not observed in all SNP, but one block haplotype was significantly associated with AS. The pairwise analysis of the rs8126528/rs2150414/rs6517532 alleles found that the G-A-A haplotype (OR 2.92, 95 % CI 1.48-3.55; p = 0.0002, permuted p = 0.0332) significantly increased the risk of AS in comparison with the G-A-G, A-A-A and G-G-A carriers. In conclusion, the study results define a novel risk haplotypes in 21q22 that was associated with AS in the Chinese Guangxi Zhuang population. The findings was consistent with previous genetic and functional studies that point at variants of the BRWD1 and/or PSMG1 loci as interesting genetic factors contributing to AS.

Analysis of clinicopathologic and imaging features of dual-phenotype hepatocellular carcinoma.

Dual-phenotype hepatocellular carcinoma (DPHCC) is a new subtype of hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between the computerized tomography scan (CT) imaging and clinicopathologic features of DPHCC. The CT imaging and clinicopathologic data of 97 HCC cases who underwent radical resection were collected retrospectively. The CT imaging feature was evaluated by the ratio of the average CT value of tumor to liver (TLR) in the plain scan, arterial, portal vein and delayed phases. The association between CT imaging and clinicopathologic features was analyzed using the t-test or chi-square test. Univariate and multivariate recurrence-free survival (RFS) analysis and overall survival (OS) were performed. The positive rates of cytokeratin 7 (CK7) and CK19 were 35.1% and 20.6% respectively. The positive rate of CK19 was significantly higher in cases with age < 47 years (P = 0.005), tumor diameter > 4 cm (P = 0.016) or AFP ≥ 400 ng/ml (P = 0.007). The TLR in the portal vein phase was significantly lower in CK19 positive group (P = 0.024). The recurrence risk was significantly higher in cases with CK19 positive (HR: 2.17, 95% CI 1.16 to 4.04, P = 0.013), tumor diameter > 4 cm (HR: 2.05, 95% CI 1.11 to 3.78, P = 0.019), AFP ≥ 400 ng/ml (HR: 2.50, 95% CI 1.37 to 4.54, P = 0.002) or CA199 ≥ 37 U/ml (HR: 2.23, 95% CI 1.12 to 4.42, P = 0.020). However, imaging features, pathological subtype, CK7 or CK19 expression were not significantly related to HCC OS in the univariate and multivariate analysis (all P > 0.05). The expression of CK19 may be associated with the enhancement feature of the portal vein phase CT image, and CK19 positive may suggest a worse RFS.

Sarcosine dehydrogenase as an immune infiltration-associated biomarker for the prognosis of hepatocellular carcinoma.

This study was aimed to investigate the prognostic value and clinical significance of sarcosine dehydrogenase (SARDH) in hepatocellular carcinoma (HCC) and to explore the underlying mechanisms. The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), HPA and CPTAC databases were adopted to analyze the expression of SARDH mRNA and protein between normal liver tissue and HCC, and examine their relationship with clinicopathological features. Kaplan-Meier analysis, Cox regression, as well as nomogram were adopted to explore the prognostic value of SARDH in HCC. Gene Ontology (GO), Kyoto Gene and Genome Encyclopedia (KEGG) together with Gene Set Enrichment Analysis (GSEA) were adopted to analyze the molecular mechanisms and biological functions of SARDH in HCC; while MethSurv, STRING, GeneMANIA, TIMER database data and single-sample gene set enrichment analysis (ssGSEA) algorithm were used for other bioinformatic analysis. Furthermore, immunohistochemistry was used to verify the expression of SARDH. Compared to normal liver tissue, SARDH expression was markedly lower in HCC. A lower SARDH expression was linked with Pathologic T stage (T3&T4), pathologic stage (Stage III&IV), and histologic grade (G3&4), which further indicates worse prognosis. Besides, results of bioinformatic analysis proved that SARDH expression was correlated with immune infiltration. In addition, SARDH hypermethylation was related to a poorer prognosis. SARDH expression was related to several key genes in the Ferroptosis pathway.

Correlation between ABO blood group and prognosis of hepatectomy for hepatitis B virus-associated hepatocellular carcinoma.

BACKGROUND: The relationship between ABO blood group and prognosis of patients with hepatocellular carcinoma (HCC) remains unclear. We investigated the relationship between prognosis and ABO blood group in patients with hepatitis B-associated HCC after radical hepatectomy. METHODS: The medical records of 874 patients with hepatitis B-associated HCC who underwent radical liver tumor resection were retrospectively collected. Cox proportional risk models were constructed for analysis, and the patient data were further balanced using propensity score matching (PSM) analysis to assess the impact of ABO blood group on the prognosis of patients with hepatitis B-associated HCC. RESULTS: In univariate Cox regression analysis, the overall survival (OS) of non-A blood type group vs. A blood type group [hazard ratio (HR) (95% confidence interval [CI]) = 1.504 (1.003-2.255), P = 0.048], in multivariate Cox regression analysis the OS of non-A blood type group versus A blood type group [HR (95% CI) = 1.596 (1.054-2.417), P = 0.027]. After PSM, the baseline information was more balanced between the two groups, yielding the same results as above [HR (95% CI) = 1.550 (1.012-2.373), P = 0.044]. CONCLUSION: The difference in OS after radical hepatectomy in patients with hepatitis B-associated HCC was statistically significant in terms of ABO blood group, OS was lower in patients with non-A blood group than in patients with A blood group.

Massive Hepatocellular Carcinoma with Situs Inversus Totalis Achieved a Complete Response Following Camrelizumab Plus Apatinib and Combined with Two-Stage Hepatectomy: A Case Report.

Situs inversus totalis (SIT) is a rare congenital condition in which abdominal and thoracic organs are transposed from normal positions. Two-stage hepatectomy (TSH) combined with translational therapy for hepatocellular carcinoma (HCC) with SIT has been rarely reported. We report a 41-year-old man with giant hepatocellular carcinoma (71 mm × 55 mm × 51 mm) whose future residual liver (FLR) and standard liver volume (SLV) ratio at first diagnosis was 37.4%. Preoperative volume assessment of portal vein ligation (PVL) revealed inadequate hypertrophy of FLR. After a multidisciplinary group discussion (MDT), the patient decided to follow conversion therapy. Three months later, ratio of the FLR/SLV increased from 37.4% to 71% after operation, which met the surgical requirements. Second hepatectomy, right lobectomy was successful. There was no recurrence after six months of follow-up. In our case, conversion therapy appears to be effective in maintaining residual liver hyperplasia, reducing tumor load, and preventing tumor progression in patients with large HCC during TSH.