Patterns of Cytogenomic Findings from a Case Series of Recurrent Pregnancy Loss Provide Insight into the Extent of Genetic Defects Causing Miscarriages.

Background A retrospective study was performed to evaluate the patterns of cytogenomic findings detected from a case series of products of conception (POC) in recurrent pregnancy loss (RPL) over a 16-year period from 2007 to 2023. Results This case series of RPL was divided into a single analysis (SA) group of 266 women and a consecutive analysis (CA) group of 225 women with two to three miscarriages analyzed. Of the 269 POC from the SA group and the 469 POC from the CA group, a spectrum of cytogenomic abnormalities of simple aneuploidies, compound aneuploidies, polyploidies, and structural rearrangements/pathogenic copy number variants (pCNVs) were detected in 109 (41%) and 160 cases (34%), five (2%) and 11 cases (2%), 35 (13%) and 36 cases (8%), and 10 (4%) and 19 cases (4%), respectively. Patterns with recurrent normal karyotypes, alternating normal and abnormal karyotypes, and recurrent abnormal karyotypes were detected in 74 (33%), 71 (32%), and 80 (35%) of consecutive miscarriages, respectively. Repeat aneuploidies of monosomy X and trisomy 16, triploidy, and tetraploidy were detected in nine women. Conclusions A comparable spectrum of cytogenomic abnormalities was noted in the SA and CA groups of RPL. A skewed likelihood of 2/3 for recurrent normal and abnormal karyotypes and 1/3 for alternating normal and abnormal karyotypes in consecutive miscarriages was observed. Routine cytogenetic analysis should be performed for consecutive miscarriages. Further genomic sequencing to search for detrimental and embryonic lethal variants causing miscarriages and pathogenic variants inducing aneuploidies and polyploidies should be considered for RPL with recurrent normal and abnormal karyotypes.

[Retracted] MicroRNA­744 suppresses cell proliferation and invasion of papillary thyroid cancer by directly targeting NOB1.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the cell migration and invasion assay data shown in Fig. 5C were strikingly similar to data appearing in different form in other articles by different authors at different research institutes. Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 19: 1903­1910, 2019; DOI: 10.3892/mmr.2019.9826].

Integrated exome sequencing and microarray analyses detected genetic defects and underlying pathways of hepatocellular carcinoma.

We performed whole exome sequencing (WES) and microarray analysis to detect somatic variants and copy number alterations (CNAs) for underlying mechanisms in a case series of hepatocellular carcinoma (HCC) with paired DNA samples from tumor and adjacent nontumor tissues. Clinicopathologic findings based on Edmondson-Steiner (E-S) grading, Barcelona-Clinic Liver Cancer (BCLC) stages, recurrence, and survival status and their associations with tumor mutation burden (TMB) and CNA burden (CNAB) were evaluated. WES from 36 cases detected variants in the TP53, AXIN1, CTNNB1, and SMARCA4 genes, amplifications of the AKT3, MYC, and TERT genes, and deletions of the CDH1, TP53, IRF2, RB1, RPL5, and PTEN genes. These genetic defects affecting the p53/cell cycle control, PI3K/Ras, and ß-catenin pathways were observed in approximately 80% of cases. A germline variant in the ALDH2 gene was detected in 52% of the cases. Significantly higher CNAB in patients with poor prognosis by E-S grade III, BCLC stage C, and recurrence than patients with good prognosis by grade III, stage A, grade III and nonrecurrence was noted. Further analysis on a large case series to correlate genomic profiling with clinicopathologic classifications could provide evidence for diagnostic interpretation, prognostic prediction, and target intervention on involved genes and pathways.

Cytogenomic Characterization of Giant Ring or Rod Marker Chromosome in Four Cases of Well-Differentiated and Dedifferentiated Liposarcoma.

Chromosome and array comparative genomic hybridization (aCGH) analyses were performed on two cases of well-differentiated liposarcoma (WDLPS) and two cases of dedifferentiated liposarcoma (DDLPS). The results revealed the characteristic giant ring (GR) or giant rod marker (GRM) chromosomes in all four cases and amplification of numerous somatic copy number alterations (SCNAs) involving a core segment of 12q14.1q15 and other chromosomal regions in three cases. The levels of amplification for oncogenes OS9, CDK4, HMGA2, NUP107, MDM2, YEATS4, and FRS2 at the core segment or other SCNAs should be characterized to facilitate pathologic correlation and prognostic prediction. Further studies for the initial cellular crisis event affecting chromosome intermingling regions for cell-type specific gene regulation may reveal the underlying mutagenesis mechanism for GR and GRM in WDLPS and DDLPS.

Correlating genomic copy number alterations with clinicopathologic findings in 75 cases of hepatocellular carcinoma.

BACKGROUND: Oligonucleotide array comparative genomic hybridization (aCGH) analysis has been used for detecting somatic copy number alterations (CNAs) in various types of tumors. This study aimed to assess the clinical utility of aCGH for cases of hepatocellular carcinoma (HCC) and to evaluate the correlation between CNAs and clinicopathologic findings. METHODS: aCGH was performed on 75 HCC cases with paired DNA samples from tumor and adjacent nontumor tissues. Survival outcomes from these cases were analyzed based on Barcelona-Clinic Liver Cancer Stage (BCLC), Edmondson-Steiner grade (E-S), and recurrence status. Correlation of CNAs with clinicopathologic findings was analyzed by Wilcoxon rank test and clustering vs. K means. RESULTS: The survival outcomes indicated that BCLC stages and recurrence status could be predictors and E-S grades could be a modifier for HCC. The most common CNAs involved gains of 1q and 8q and a loss of 16q (50%), losses of 4q and 17p and a gain of 5p (40%), and losses of 8p and 13q (30%). Analyses of genomic profiles and clusters identified that losses of 4q13.2q35.2 and 10q22.3q26.13 seen in cases of stage A, grade III and nonrecurrence were likely correlated with good survival, while loss of 1p36.31p22.1 and gains of 2q11.2q21.2 and 20p13p11.1 seen in cases of stage C, grade III and recurrence were possibly correlated with worst prognosis. CONCLUSIONS: These results indicated that aCGH analysis could be used to detect recurrent CNAs and involved key genes and pathways in patients with HCC. Further analysis on a large case series to validate the correlation of CNAs with clinicopathologic findings of HCC could provide information to interpret CNAs and predict prognosis.

Homer2 and Homer3 Act as Novel Biomarkers in Diagnosis of hepatitis B virus-induced Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality worldwide. Early detection of HCC can significantly improve patients' outcomes. An increasing number of studies have validated that Homer is dysregulated in cancers and may serve as diagnostic markers. In the present study, we investigated the expression profile and diagnostic significance of Homer2 and Homer3 in hepatitis B virus-induced HCC (HBV-HCC). Methods: Quantitative real-time PCR (QRT-PCR), western blot analysis and immunohistochemistry analysis. Results: Homer2 and Homer3 were downregulated in HCC. The expression of Homer2 was associated with tumor differentiation grade (P= 0.012) and total protein (TP) level (P= 0.032). Homer3 was related to tumor size (P= 0.010), tumor nodes (P= 0.026) and γ-glutamyl transferase (GGT) level (P= 0.001). The receiver operating characteristic curve analyses indicated that the combination of Homer2, Homer3 and AFP possessed a high accuracy (AUC=0.900) to diagnose HCC cases from healthy controls. Conclusion: Our data indicated that Homer2 and Homer3 were downregulated in HCC and might be potential diagnostic marker for HCC.

Detection of cytogenomic abnormalities by OncoScan microarray assay for products of conception from formalin-fixed paraffin-embedded and fresh fetal tissues.

BACKGROUND: The OncoScan microarray assay (OMA) using highly multiplexed molecular inversion probes for single nucleotide polymorphism (SNP) loci enabled the detection of cytogenomic abnormalities of chromosomal imbalances and pathogenic copy number variants (pCNV). The small size of molecular inversion probes is optimal for SNP genotyping of fragmented DNA from fixed tissues. This retrospective study evaluated the clinical utility of OMA as a uniform platform to detect cytogenomic abnormalities for pregnancy loss from fresh and fixed tissues of products of conception (POC). RESULTS: Fresh specimens of POC were routinely subjected to cell culture and then analyzed by karyotyping. POC specimens with a normal karyotype (NK) or culture failure (CF) and from formalin-fixed paraffin-embedded (FFPE) tissues were subjected to DNA extraction for OMA. The abnormality detection rate (ADR) by OMA on 94 cases of POC-NK, 38 cases of POC-CF, and 35 cases of POC-FFPE tissues were 2% (2/94), 26% (10/38), and 57% (20/35), respectively. The detected cytogenomic abnormalities of aneuploidies, triploidies and pCNV accounted for 50%, 40% and 10% in POC-CF and 85%, 10% and 5% in POC-FFPE, respectively. False negative result from cultured maternal cells and maternal cell contamination were each detected in one case. OMA on two cases with unbalanced structural chromosome abnormalities further defined genomic imbalances and breakpoints. CONCLUSION: OMA on POC-CF and POC-FFPE showed a high diagnostic yield of cytogenomic abnormalities. This approach circumvented the obstacles of CF from fresh specimens and fragmented DNA from fixed tissues and provided a reliable and effective platform for detecting cytogenomic abnormalities and monitoring true fetal result from maternal cell contamination.

Exome sequencing analysis on products of conception: a cohort study to evaluate clinical utility and genetic etiology for pregnancy loss.

PURPOSE: Pregnancy loss ranging from spontaneous abortion (SAB) to stillbirth can result from monogenic causes of Mendelian inheritance. This study evaluated the clinical application of exome sequencing (ES) in identifying the genetic etiology for pregnancy loss. METHODS: A cohort of 102 specimens from products of conception (POC) with normal karyotype and absence of pathogenic copy-number variants were selected for ES. Abnormality detection rate (ADR) and variants of diagnostic value correlated with SAB and stillbirth were evaluated. RESULTS: ES detected 6 pathogenic variants, 16 likely pathogenic variants, and 17 variants of uncertain significance favor pathogenic (VUSfp) from this cohort. The ADR for pathogenic and likely pathogenic variants was 22% and reached 35% with the inclusion of VUSfp. The ADRs of SAB and stillbirth were 36% and 33%, respectively. Affected genes included those associated with multisystem abnormalities, neurodevelopmental disorders, cardiac anomalies, skeletal dysplasia, metabolic disorders, and renal diseases. CONCLUSION: These results supported the clinical utility of ES for detecting monogenic etiology of pregnancy loss. The identification of disease-associated variants provided information for follow-up genetic counseling of recurrence risk and management of subsequent pregnancies. Discovery of novel variants could provide insight for underlying molecular mechanisms causing fetal death.

Cytogenomic Abnormalities in 19 Cases of Salivary Gland Tumors of Parotid Gland Origin.

Salivary gland tumors (SGTs) of parotid origin are a group of diverse neoplasms which are difficult to classify due to their rarity and similar morphologic patterns. Chromosome analysis can detect clonal abnormalities, and array comparative genomic hybridization (aCGH) analysis can define copy number alterations (CNAs) from tumor specimens. Of the 19 cases of various types of SGTs submitted for cytogenomic analyses, an abnormal clone was detected in nine cases (47%), and CNAs were detected in 14 cases (74%). Recurrent rearrangements involving the PLAG1 gene at 8q12, recurrent CNAs including deletions of 6q, 9p (CDKN2A), and 17p (TP53), loss of Y chromosome, and gain of chromosome 7 were defined from these cases. Combined karyotyping and aCGH analyses could improve diagnostic yield. Future study for more precisive correlation of SGT classification with cytogenomic abnormalities will facilitate better diagnosis and treatment.

Molecular and clinicopathologic characterization of intravenous leiomyomatosis.

Intravenous leiomyomatosis (IVL) is an unusual uterine smooth muscle proliferation that can be associated with aggressive clinical behavior despite a histologically benign appearance. It has some overlapping molecular characteristics with both uterine leiomyoma and leiomyosarcoma based on limited genetic data. In this study, we assessed the clinical and morphological characteristics of 28 IVL and their correlation with molecular features and protein expression, using array comparative genomic hybridization (aCGH) and Cyclin D1, p16, phosphorylated-Rb, SMARCB1, SOX10, CAIX, SDHB and FH immunohistochemistry. The most common morphologies were cellular (n = 15), usual (n = 11), and vascular (n = 5; including 3 cellular IVL showing both vascular and cellular features). Among the immunohistochemical findings, the most striking was that all IVL showed differential expression of either p16 or Cyclin D1 in comparison to surrounding nonneoplastic tissue. Cytoplasmic phosphorylated-Rb was present in all but one IVL with hyalinization. SMARCB1, FH, and SDHB were retained; S0X10 and CAIX were not expressed. The most common genetic alterations involved 1p (39%), 22q (36%), 2q (29%), 1q (25%), 13q (21%), and 14q (21%). Hierarchical clustering analysis of recurrent aberrations revealed three molecular groups: Groups 1 (29%) and 2 (18%) with associated del(22q), and Group 3 (18%) with del(10q). The remaining IVL had nonspecific or no alterations by aCGH. Genomic index scores were calculated for all cases and showed no significant difference between the 14 IVL associated with aggressive clinical behavior (extrauterine extension or recurrence) and those without (median scores 5.15 vs 3.5). Among the 5 IVL associated with recurrence, 4 had a vascular morphology and 3 had alterations of 8q. Recurrent chromosome alterations detected herein overlap with those observed in the spectrum of uterine smooth muscle tumors and involve genes implicated in mesenchymal tumors at different sites with distinct morphological features.

Role of BCYRN1 in hepatocellular carcinoma pathogenesis by lncRNA-miRNA-mRNA network analysis and its diagnostic and prognostic value.

Aim: This study aimed to excavate the roles of BCYRN1 in hepatocellular carcinoma (HCC). Methods: A comprehensive strategy of microarray data mining, computational biology and experimental verification were adopted to assess the clinical significance of BCYRN1 and identify related pathways. Results:BCYRN1 was upregulated in HCC and its expression was positively associated with both tumor, node, metastasis and worse survival rate in patients with HCC. Through combing plasma BCYRN1 with alpha fetoprotein, the diagnosis of HCC was remarkably improved. BCYRN1 may regulate some cancer-related pathways to promote HCC initiation via an lncRNA-miRNA-mRNA network. Conclusion: Our results propose BCYRN1 as a potential diagnostic and prognostic biomarker and offer a novel perspective to explore the etiopathogenesis of HCC.

MicroRNA­744 suppresses cell proliferation and invasion of papillary thyroid cancer by directly targeting NOB1.

MicroRNAs (miRs) serve important roles in the formation and progression of papillary thyroid cancer (PTC) by regulating numerous physiological and pathological behaviours. Thus, investigating the functional roles of specific miRNAs in PTC may contribute in identifying effective therapeutic targets for the management of patients with PTC. miR­744 is emerging as a cancer­associated miRNA in numerous types of human cancers; however, the expression and specific functions of miR­744 in PTC are yet to be determined, and the mechanism underlying the regulatory roles of miR­744 in PTC remains unknown. In the present study, miR­744 expression was significantly decreased in PTC tissues and cell lines, as detected by reverse transcription­quantitative polymerase chain reaction. miR­744 restoration inhibited cell proliferation and invasion in PTC. Bioinformatics analysis predicted NIN1 (RPN12) binding protein 1 homolog (NOB1) as a potential target of miR­744. Subsequent experiments validated NOB1 as a direct target gene of miR­744 in PTC. Furthermore, NOB1 was upregulated in PTC tissues and negatively correlated with miR­744 expression. NOB1 overexpression could counteract miR­744­mediated antitumor effects on PTC cells. In summary, these findings indicated that miR­744 may inhibit the progression of PTC by directly targeting NOB1. The identification of the miR­744/NOB1 axis may provide insight into potential targets for the treatment of patients with PTC and improve their prognosis.

Down-regulation of long non-coding RNA GAS5-AS1 and its prognostic and diagnostic significance in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common solid tumor in global range, with high degree of malignancy and poor prognosis. But the relationship between the expression of GAS5-AS1 and HCC is not documented. This study aimed to profile GAS5-AS1 expression signature and then to explore its clinical significance in HCC. METHODS: Quantitative real-time PCR (RT-qPCR) was performed to detect the expression of GAS5-AS1 in 83 pairs of HCC surgical tissues and adjacent normal liver tissues. We also performed RT-qPCR on plasma samples of 156 patients and 58 healthy controls. RESULTS: We found that GAS5-AS1 was down-regulated in HCC tissues (P< 0.01). Correlation analysis showed that the expression of GAS5-AS1 was notably associated with differentiation (High/Moderate vs Low, P= 0.031), tumor-node-metastasis (TNM) stage (I∼II vs III∼IV, P= 0.020) and glucose levels (< 6.2 vs≧ 6.2, P= 0.047) in HCC patients. The overall survival analysis showed that patients with lower GAS5-AS1 expression had a relatively poor prognosis. Univariate and multivariate analysis elaborated that GAS5-AS1 was an independent prognostic factor for HCC patients. The area under the ROC (AUCROC) demonstrated that GAS5-AS1 presented a high accuracy (AUC = 0.824, 95% CI: 0.741-0.906) for distinguishing HCC from the cirrhosis. When differentiating HCC cases with AFP < 200 ng/ml from the cirrhosis and hepatitis B whose AFP levels were also below 200 ng/ml, GAS5-AS1 had the high sensitivity (89.5%, 89.5%, respectively). CONCLUSIONS: GAS5-AS1 could be considered as a potential prognostic and diagnostic marker in HCC. However, the potential clinical application value of GAS5-AS1 still needs to be further illustrated.

Clinical and Diagnostic Significance of Homer1 in hepatitis B virus-induced Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is a malignant tumor worldwide. Attributed to the lack of early diagnosis index, most patients are diagnosed in their late stage. Homer1, as a member of scaffold protein family, is made up of two different isoforms: Homer1a and Homer1b/c. More and more evidences show that Homer1 is dysregulated in cancers. Here, in this study, we investigated the expression profile, clinical, diagnostic and prognostic significance of Homer1 in hepatitis B virus-induced HCC (HBV-HCC). Methods: We first tested the expression of Homer1 in HCC cell lines by quantitative real-time PCR (qRT-PCR), western blot. Then, 86 pairs of tumorous and adjacent normal tissues from HCC together with a total number of 245 peripheral blood samples were enrolled to check the expression levels of Homer1 by quantitative real-time PCR (qRT-PCR). Results: The results revealed that the levels of Homer1 were both downregulated in HCC cell line and tissue and were associated with tumor size, but were not related to the prognosis of HBV-HCC. Receiver-operating characteristic curve analyses indicated that the sensitivity of Homer1 to differentiate HCC patients from the controls was high to 100.0% and the combination of Homer1 and AFP got a higher prediction value of HCC (AUC=0.890). Conclusion: Our data highlighted that Homer1 played a critical role in HCC tumorigenesis and might be a potential diagnostic marker for HCC.

Antitumor and anti-metastatic mechanisms of Rhizoma paridis saponins in Lewis mice.

Lung cancer is one of the most common causes of death in the world. Rhizoma paridis saponins (RPS) have been found to show inhibition of pulmonary adenoma in previous research. However, the detailed mechanisms of RPS from a holistic view have not been established. In this study, Lewis pulmonary adenoma mice were successfully established to analyze the pathways involved in RPS intervening tumor formation and progression. As a result, RPS inhibited levels of cytokines or receptors such as VEGFD, VEGFR3, RAGE, IL6R, IL17BR, and CXCL16 which were regarded as the initiators induced tumor cell proliferation, adhesion, angiogenesis, and invasion. Meanwhile, RPS raised the content of SOD and CAT enzymes and thereby inhibited the aberrantly active NF-κB, and phosphorylation of PI3K/Akt and MAPK (including p38, Erk1/2, and JNK) signaling pathways. Soon after, RPS changed mRNA expression of nuclear factors containing NF-κB, HIF-1A, STAT3, and Jun, and consequentially suppressed the expression of angiogenesis, lymphangiogenesis, adhesion, inflammation, and invasion enzymes. In conclusion, this research provided a holistic view to understand the multi-target antitumor mechanisms of RPS which promoted the application of RPS in the future.

Inhibition of miR-155, a therapeutic target for breast cancer, prevented in cancer stem cell formation.

BACKGROUND: Breast cancer is a common cancer in women of worldwide. Cancer cells with stem-like properties played important roles in breast cancer, such as relapse, metastasis and treatment resistance. Micro-RNA-155 (miR-155) is a well-known oncogenic miRNA overexpressed in many human cancers. METHODS: The expression levels of miR-155 in 38 pairs of cancer tissues and adjacent normal tissues from breast cancer patients were detected using quantitative real-time PCR. The invasive cell line MDA-MB-231 was used to quantify the expression of miR-155 by tumor-sphere forming experiment. Soft agar colony formation assay and tumor xenografts was used to explore whether the inhibition of miR-155 could reduce proliferation of cancer cells in vivo and vitro. RESULTS: In the study, we found miR-155 was upregulated in BC. Soft agar colony formation assay and tumor xenografts showed inhibition of miR-155 could significantly reduce proliferation of cancer cells in vivo and vitro, which confirmed that miR-155 is an effective therapeutic target of breast cancer. Sphere-forming experiment showed that overexpression of miR-155 significantly correlated with stem-like properties. Expressions of ABCG2, CD44 and CD90 were repressed by inhibition of miR-155, but CD24 was promoted. Interestingly, inhibition of miR-155 rendered MDA-MB-231 cells more sensitive to Doxorubicinol, which resulted in an increase of inhibition rate from 20.23% to 68.72%. Expression of miR-155 not only was a therapeutic target but also was associated with cancer stem cell formation and Doxorubicinol sensitivity. CONCLUSIONS: Our results underscore the importance of miR-155 as a therapeutic target and combination of Doxorubicinol and miR-155-silencing would be a potential way to cure breast cancer.

The prognostic significance of long noncoding RNAs in non-small cell lung cancer: a meta-analysis.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The overall 5-year survival rate of patients is extremely low and to find a new marker is urgently needed. Numerous studies indicate that long noncoding RNAs (lncRNAs) abnormally express in cancers. However, the results have been disputed, especially in the aspects of tumor prognosis. Therefore, we performed this meta-analysis to systematically summarize the relationship between lncRNAs expression and NSCLC. A total of 34 eligible studies including 30 on overall survival, 10 on progression-free survival and 23 on clinicopathological features were identified from the databases. Our results indicated that the levels of lncRNAs were associated with the overall survival (OS; hazard ratios [HR], 1.43; 95% confidence interval [95% CI], 1.17-1.76; P < 0.001). However, there was no relationship between lncRNAs and progression-free survival (PFS; hazard ratios [HR], 1.55; 95% confidence interval [95% CI], 0.91-2.63; P = 0.11). Moreover, lncRNAs were related to lymph node metastasis (odds ratios [OR], 1.70; 95% confidence interval [95% CI], 1.03-2.80; P = 0.04), while no association was observed with other characteristics. In conclusion, our present meta-analysis indicated that lncRNAs transcription levels may serve as a promising marker for prognosis of patients with NSCLC.

Prognostic and Diagnostic Significance of SDPR-Cavin-2 in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumor worldwide. Due to the lack of early prediction marker, numerous patients were diagnosed in their late stage. The family of cavins plays important roles in caveolae formation and cellular processes. Cavin-2, one of the members of cavins, has been reported as a suppresser in cancers. In this study, we have investigated its expression pattern and clinical significance in HCC. METHODS: RT­qPCR was performed to detect the expression of cavin-2. RESULTS: Cavin-2 was down-regulated in HCC and associated with tumor differentiation (r=-0.275, P=0.013) and tumor-node-metastasis (TNM) stage (r=-0.216, P=0.035). The Overall survival analysis showed that patients with lower cavin-2 expression had a relatively poor prognosis. Meanwhile, the multivariate analysis revealed that cavin-2 was an independent prognostic factor. The receiver operating characteristic curve analyses indicated that plasma cavin-2 presented a high accuracy (AUC=0.727, 0.865, 0.901) for diagnosing HCC cases from controls, hepatitis B and cirrhosis patients, respectively. Meanwhile, plasma cavin-2 showed a high sensitivity (88.4%, 89.9%) for detecting HCC with the serum α­fetoprotein (AFP) levels below 200 ng/ml from those hepatitis B and cirrhosis cases. CONCLUSION: Our data suggested that cavin-2 might be considered as a potential prognostic and diagnostic indicator in HCC.

Potential diagnostic value of lncRNA SPRY4-IT1 in hepatocellular carcinoma.

The manifestation of hepatocellular carcinoma (HCC) involves a multi-factor, multi-step and complex process. Due to the lack of early prediction indices, numerous patients are diagnosed in their late stage. Recently, research in the field of non-coding RNAs (ncRNAs) has changed the original idea that ncRNA genes are just ̔noise̓. Cumulative evidence shows that long non-coding RNAs (lncRNAs) among ncRNAs play an increasingly important role in epigenetics, pre-transcription and post-transcription. In the present study, we focused on the expression pattern of lncRNA SPRY4 intronic transcript 1 (SPRY4-IT1) and its clinical significance in HCC diagnostics. We analyzed the expression, its association with clinical characteristics and the diagnostic value of SPRY4-IT1 using HCC tissues, cell lines and plasma. The levels of SPRY4-IT1 were upregulated in HCC and were associated with tumor differentiation (r=0.249, p=0.039), tumor size (r=0.258, p=0.024) and tumor-node-metastasis (TNM) stage (r=0.287, p=0.015). Meanwhile, the sensitive of SPRY4-IT1 was 87.3% in differentiating HCC patients from controls. Our data suggest that SPRY4-IT1 plays a critical role in HCC tumorigenesis and may be considered as a potential diagnostic indicator in HCC.

Curcumin alleviated the toxic reaction of Rhizoma Paridis saponins in a 45-day subchronic toxicological assessment of rats.

Rhizoma Paridis saponins (RPS), as steroid saponins, are the main components in Paris polyphylla. Curcumin (diferuloylmethane) is the most important component in the spice turmeric. In our previous research, RPS exhibited side effects such as nausea, vomiting, diarrhea, and so forth. Combination with curcumin not only alleviated the toxicity and gastric stimulus induced by RPS, but also improved the quality life of mice bearing tumor cells and enhanced their anticancer effect. This study evaluated subchronic toxicity of 45th dietary of RPS and curcumin on histopathology, biochemistry, and antioxidant index. As a result, RPS-treatment caused a slight liver injury (the elevation of serum AST, alkaline phosphatase (AKP), alanine transaminase (ALT), and gamma glutamyl transpeptidase (γ-GT), histopathological changes in liver section), oxidative stress (the enhancement of reactive oxygen species (ROS), malondialdehyde (MDA), and 8-hydroxy-2-deoxyguanosine (8-OHdG), separation of thioredoxin (Trx) and thioredoxin-interacting protein (TXNIP), but enhancement of heme oxygenase-1 (HO-1), glutathione S-transferase (GST), and nuclear factor-regulated factor 2 (Nrf2)), and inflammation (up-regulation of cyclooxygenase-2 (COX-2), interleukin-1ß (IL-1ß), and nuclear factor kappaB (NF-κB)). However, these changes were alleviated through co-treatment with curcumin. In conclusion, our work provided useful data for further research and new drug exploration of RPS and curcumin. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1935-1943, 2016.