Low FHL1 expression indicates a good prognosis and drug sensitivity in ovarian cancer.

Chemotherapy resistance is the main reason for the poor prognosis of ovarian cancer (OC). FHL1 is an important tumour regulator, but its relationship with the prognosis, drug resistance, and tumour microenvironment of OC is unknown. Immunohistochemistry was used to determine FHL1 expression in OC. Kaplan‒Meier plotter was used for survival analysis. The value of gene expression in predicting drug resistance was estimated using the area under the curve (AUC). Bivariate correlation was used to determine the coexpression of two genes. Functional cluster and pathway enrichment were used to uncover hidden signalling pathways. The relationship between gene levels and the tumour microenvironment was visualised through the ggstatsplot and pheatmap packages. The mRNA and protein levels of FHL1 were downregulated in 426 and 100 OC tissues, respectively. Low FHL1 expression was correlated with good progression-free survival (PFS), postprogression survival, and overall survival (OS) in 1815 OC patients, and was further confirmed to be associated with good OS by immunohistochemistry in 152 OC tissues. Furthermore, FHL1 was downregulated in drug-sensitive tissues, while its high expression predicted drug resistance (AUC > 0.65). Mechanistically, FHL1 was coexpressed with FLNC, CAV1, PPP1R12B, and FLNA at the mRNA and protein levels in 558 and 174 OC tissues, respectively, and their expression was downregulated in OC. Additionally, very strong coexpression of FHL1 with the four genes was identified in at least 23 different tumours. Low expression of the four genes was associated with good PFS, and the combination of FHL1 with the four genes provided better prognostic power. Meanwhile, the expression of all five genes was strongly and positively associated with the abundance of macrophages. Low FHL1 expression acts as a favourable factor in OC, probably via positive coexpression with FLNC, CAV1, PPP1R12B, and FLNA.

Low expression of GOT2 promotes tumor progress and predicts poor prognosis in hepatocellular carcinoma.

Background: To explore the biological function and the underlying mechanisms of GOT2 in hepatocellular carcinoma (HCC). Materials & methods: The expression level and prognostic value of GOT2 were examined using International Cancer Genome Consortium and International Cancer Proteogenome Consortium databases. The cell counting kit-8 method, clone formation, Transwell® assays and western blotting were used to evaluate the effects of GOT2 on the biological function and autophagy of HCC cells. Results: The expression of GOT2 was downregulated in HCC tissues and correlated with poor prognosis of HCC patients. Knockdown of GOT2 promoted proliferation, migration and invasion of HCC cells and promoted cells' proliferation by inducing autophagy. Conclusion: GOT2 plays a tumor-inhibitory role in HCC and may be a potential therapeutic target for HCC.

Identification and verification of novel ferroptosis biomarkers predicts the prognosis of hepatocellular carcinoma.

BACKGROUND: Big data mining and experiments are widely used to mine new prognostic markers. METHODS: Candidate genes were identified from CROEMINE and FerrDb. Kaplan-Meier survival and Cox regression analysis were applied to assess the association of genes with Overall survival time (OS) and Disease-free survival time (DFS) in two HCC cohorts. Real-time quantitative polymerase chain reaction (RT-qPCR) and Immunohistochemistry were performed in HCC samples. RESULTS: 21 and 15 genes that can predict OS and DFS, which had not been reported before, were identified from 719 genes, respectively. Survival analysis showed elevated mRNA expression of GLMP, SLC38A6, and WDR76 were associated with poor prognosis, and three genes combination signature was an independent prognostic factor in HCC. RT-qPCR and Immunohistochemistry confirmed the results. CONCLUSIONS: We established a novel computational process, which identified the expression levels of GLMP, SLC38A6, and WDR76 as potential ferroptosis-related biomarkers indicating the prognosis of HCC.

COVID-19 vaccination effectiveness and safety in vulnerable populations: a meta-analysis of 33 observational studies.

Background: Even 3 years into the COVID-19 pandemic, questions remain about how to safely and effectively vaccinate vulnerable populations. A systematic analysis of the safety and efficacy of the COVID-19 vaccine in at-risk groups has not been conducted to date. Methods: This study involved a comprehensive search of PubMed, EMBASE, and Cochrane Central Controlled Trial Registry data through 12 July 2022. Post-vaccination outcomes included the number of humoral and cellular immune responders in vulnerable and healthy populations, antibody levels in humoral immune responders, and adverse events. Results: A total of 23 articles assessing 32 studies, were included. The levels of IgG (SMD = -1.82, 95% CI [-2.28, -1.35]), IgA (SMD = -0.37, 95% CI [-0.70, -0.03]), IgM (SMD = -0.94, 95% CI [-1.38, -0.51]), neutralizing antibodies (SMD = -1.37, 95% CI [-2.62, -0.11]), and T cells (SMD = -1.98, 95% CI [-3.44, -0.53]) were significantly lower in vulnerable than in healthy populations. The positive detection rates of IgG (OR = 0.05, 95% CI [0.02, 0.14]) and IgA (OR = 0.03, 95% CI [0.01, 0.11]) antibodies and the cellular immune response rates (OR = 0.20, 95% CI [0.09, 0.45]) were also lower in the vulnerable populations. There were no statistically significant differences in fever (OR = 2.53, 95% CI [0.11, 60.86]), chills (OR = 2.03, 95% CI [0.08, 53.85]), myalgia (OR = 10.31, 95% CI [0.56, 191.08]), local pain at the injection site (OR = 17.83, 95% CI [0.32, 989.06]), headache (OR = 53.57, 95% CI [3.21, 892.79]), tenderness (OR = 2.68, 95% CI [0.49, 14.73]), and fatigue (OR = 22.89, 95% CI [0.45, 1164.22]) between the vulnerable and healthy populations. Conclusion: Seroconversion rates after COVID-19 vaccination were generally worse in the vulnerable than healthy populations, but there was no difference in adverse events. Patients with hematological cancers had the lowest IgG antibody levels of all the vulnerable populations, so closer attention to these patients is recommended. Subjects who received the combined vaccine had higher antibody levels than those who received the single vaccine.

Identification of natural compound garcinone E as a novel autophagic flux inhibitor with anticancer effect in nasopharyngeal carcinoma cells.

CONTEXT: Current chemotherapeutic drugs cannot meet the treatment needs of patients with nasopharyngeal carcinoma (NPC), so urgent action is needed to discover novel chemotherapeutic agents. Our previous study revealed that garcinone E (GE) inhibited the proliferation and metastasis of NPC, suggesting that the compound might display promising anticancer activity. OBJECTIVE: To examine the mechanism underlying the anti-NPC activity of GE for the first time. MATERIALS AND METHODS: For MTS assay, NPC cells were treated with 2.5-20 µmol/L GE or dimethyl sulfoxide for 24, 48, and 72 h. Colony formation capacity, cell cycle distribution, and in vivo xenograft experiment of GE were assessed. MDC staining, StubRFP-sensGFP-LC3 observation, LysoBrite Blue staining, and immunofluorescence examined the autophagy of NPC cells after GE exposure. Western blotting, RNA-sequencing, and RT-qPCR measured protein and mRNA levels. RESULTS: GE suppressed cell viability with an IC50 of 7.64, 8.83 and 4.65 µmol/L for HK1, HONE1 and S18 cells. GE inhibited colony formation and cell cycle, increased autophagosome number, and inhibited the autophagic flux partially by blocking lysosome-autophagosome fusion, and repressed S18 xenograft growth. GE dysregulated the expression of autophagy- and cell cycle-related proteins such as Beclin-1, SQSTM1/p62, LC3, CDKs, and Cyclins. Bioinformatics GO and KEGG pathway enrichment analysis of RNA-seq showed that autophagy was enriched in differentially expressed genes upon GE treatment. DISCUSSION AND CONCLUSION: GE acts as an autophagic flux inhibitor, which may have potential chemotherapeutic use for NPC treatment and may have an application in basic research to explore the mechanisms of autophagy.

Anti-freezing, recoverable and transparent conductive hydrogels co-reinforced by ethylene glycol as flexible sensors for human motion monitoring.

Wearable flexible sensors based on conductive hydrogels have received extensive attention in the fields of electronic skin and smart monitoring. However, conductive hydrogels contain a large amount of water, which greatly affects their performances in harsh environments. It is therefore necessary to prepare hydrogel sensors that are stable at low temperatures. Herein, metal ions (MgCl2) and ethylene glycol (EG) were combined with polyvinyl alcohol (PVA) to obtain a conductive PVA/EG hydrogel with tensile strength and elongation at break of 1.1 MPa and 442.3 %, respectively, which could withstand >6000-fold its own weight. The binary solvent system composed of water and EG contributed to the excellent anti-freezing properties and long-term storage (>1 week), flexibility, and stability of the hydrogel even at -20 °C. The wearable PVA/EG hydrogel as a flexible sensor possessed desirable sensing performances with a competitive GF value of 0.725 and fatigue resistance (50 cycles) when used to monitor various human motions and physiological signals. Overall, this hydrogel sensor shows strong potential for application in the fields of human motion monitoring, written information sensing, and information encryption and transmission.

Low Expression of SLC7A11 Confers Drug Resistance and Worse Survival in Ovarian Cancer via Inhibition of Cell Autophagy as a Competing Endogenous RNA.

Drug resistance is the main cause of chemotherapy failure in ovarian cancer (OC), and identifying potential druggable targets of autophagy is a novel and promising approach to overcoming drug resistance. In this study, 131 genes associated with autophagy were identified from three autophagy-related databases, and of these, 14 were differentially expressed in 90 drug-resistant OC tissues versus 197 sensitive tissues according to the Cancer Genome Atlas ovarian cancer cohort. Among these 14 genes, SLC7A11 was significantly decreased in two paclitaxel-resistant OC cells (HeyA8-R and SKOV3-R) and in 90 drug-resistant tissues compared with their controls. In vitro overexpression of SLC7A11 significantly increased the sensitivity of HeyA8-R cells to paclitaxel, inhibited colony formation, induced apoptosis, and arrested cell cycle. Further, low SLC7A11 expression was correlated with poor overall survival (OS), progression-free survival (PFS), and post-progression survival (PPS) in 1815 OC patients. Mechanistically, SLC7A11 strongly regulated cell autophagy as a competing endogenous RNA (ceRNA) based on pan-cancer analyses of 32 tumor types. Specifically, as a ceRNA for autophagy genes STX17, RAB33B, and UVRAG, SLC7A11 was strongly and positively co-expressed with these three genes in 20, 12, and 12 different tumors, respectively, in 379 OC tissues and in 90 drug-resistant OC tissues, and the former two were significantly upregulated in SLC7A11-overexpressed HeyA8-R cells. Further, SLC7A11 induced the protein expression of other autophagy genes, such as LC3, Atg16L1, and Atg7, and the expression of the respective proteins was further increased when the cells were treated with paclitaxel. The results strongly suggest that SLC7A11 regulates autophagy via ceRNA interactions with the three abovementioned genes in pan-cancer and in drug-resistant OC. Moreover, low expression of STX17 and UVRAG also significantly predicted low OS, PFS, and PPS. The combination of SLC7A11 with STX17 was more predictive of OS and PFS than either individually, and the combination of SLC7A11 with UVRAG was highly predictive of OS and PPS. The above results indicated that decreased SLC7A11 resulted in drug resistance and effected low rates of survival in OC patients, probably via ceRNA interactions with autophagy genes, and thus the gene could serve as a therapeutic target and potential biomarker in OC.

Integrated profiling identifies ITGB3BP as prognostic biomarker for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly malignant tumor. In this study, we sought to identify a novel biomarker for HCC by analyzing transcriptome and clinical data. The R software was used to analyze the differentially expressed genes (DEGs) in the datasets GSE74656 and GSE84598 downloaded from the Gene Expression Omnibus database, followed by a functional annotation. A total of 138 shared DEGs were screened from two datasets. They were mainly enriched in the "Metabolic pathways" pathway (Padj = 8.21E-08) and involved in the carboxylic acid metabolic process (Padj = 0.0004). The top 10 hub genes were found by protein-protein interaction analysis and were upregulated in HCC tissues compared to normal tissues in The Cancer Genome Atlas database. Survival analysis distinguished 8 hub genes CENPE, SPDL1, Hyaluronan-mediated motility receptor, Rac GTPase activating protein 1, Thyroid hormone receptor interactor 13, cytoskeleton-associated protein (CKAP) 2, CKAP5, and Integrin subunit beta 3 binding protein (ITGB3BP) were considered as prognostic hub genes. Multivariate cox regression analysis indicated that all the prognostic hub genes were independent prognostic factors for HCC. Furthermore, the receiver operating characteristic curve revealed that the 8-hub genes model had better prediction performance for overall survival compared to the T stage (p = 0.008) and significantly improved the prediction value of the T stage (p = 0.002). The Human Protein Atlas showed that the protein expression of ITGB3BP was upregulated in HCC, so the expression of ITGB3BP was further verified in our cohort. The results showed that ITGB3BP was upregulated in HCC tissues and was significantly associated with lymph node metastasis.

Big Data-Based Identification of Multi-Gene Prognostic Signatures in Liver Cancer.

Simultaneous identification of multiple single genes and multi-gene prognostic signatures with higher efficacy in liver cancer has rarely been reported. Here, 1,173 genes potentially related to the liver cancer prognosis were mined with Coremine, and the gene expression and survival data in 370 samples for overall survival (OS) and 319 samples for disease-free survival (DFS) were retrieved from The Cancer Genome Atlas. Numerous survival analyses results revealed that 39 genes and 28 genes significantly associated with DFS and OS in liver cancer, including 18 and 12 novel genes that have not been systematically reported in relation to the liver cancer prognosis, respectively. Next, totally 9,139 three-gene combinations (including 816 constructed by 18 novel genes) for predicting DFS and 3,276 three-gene combinations (including 220 constructed by 12 novel genes) for predicting OS were constructed based on the above genes, and the top 15 of these four parts three-gene combinations were selected and shown. Moreover, a huge difference between high and low expression group of these three-gene combination was detected, with median survival difference of DFS up to 65.01 months, and of OS up to 83.57 months. The high or low expression group of these three-gene combinations can predict the longest prognosis of DFS and OS is 71.91 months and 102.66 months, and the shortest is 6.24 months and 13.96 months. Quantitative real-time polymerase chain reaction and immunohistochemistry reconfirmed that three genes F2, GOT2, and TRPV1 contained in one of the above combinations, are significantly dysregulated in liver cancer tissues, low expression of F2, GOT2, and TRPV1 is associated with poor prognosis in liver cancer. Overall, we discovered a few novel single genes and multi-gene combinations biomarkers that are closely related to the long-term prognosis of liver cancer, and they can be potential therapeutic targets for liver cancer.

NCALD affects drug resistance and prognosis by acting as a ceRNA of CX3CL1 in ovarian cancer.

Drug resistance, an impenetrable barrier in the treatment of ovarian cancer (OC), is often associated with poor outcomes. Hence, it is urgent to discover new factors controlling drug resistance and survival. The association between neurocalcin delta (NCALD) and cancer drug resistance is poorly understood. Here, we reveal that NCALD messenger RNA expression, probably regulated by DNA methylation and microRNAs, was significantly downregulated in at least three independent microarrays covering 633 ovarian carcinomas and 16 normal controls, which includes the Cancer Genome Atlas (TCGA) ovarian cohort. In the sub-groups of the TCGA cohort, NCALD was suppressed in 90 platinum-resistant tissues vs in 197 sensitive tissues. It is consistent with the quantitative reverse transcription polymerase chain reaction results revealing gene downregulation in carboplatin-resistant SKOV3 and HeyA8 OC cells as compared with that in controls. Low expression of NCALD predicted poor overall survival (OS) in sub-groups of 1656 patients, progression-free survival (PFS) in 1435 patients, and post-progression survival (PPS) in 782 patients according to Kaplan-Meier plotter covering 1815 OC patients. Comprehensive bioinformatic analyses strongly implicated NCALD in the regulation of drug resistance, probably via competing for endogenous RNA (ceRNA) interactions with CX3CL1 and tumor immune-microenvironment. NCALD acted as a ceRNA for CX3CL1 in 21 different cancers includes OC according to Starbase. These two genes negatively correlated with tumor purity and positively correlated with infiltration levels of neutrophils and dendritic cells in OC. The combined low expression of NCALD and CX3CL1 showed better prognosis potential for OS, PFS, and PPS in the 1815 OC patients than any of the individually tested genes. In summary, NCALD acts as a ceRNA for CX3CL1, and its downregulation may affect drug resistance and prognosis in OC. Thus, NCALD could be a new therapeutic target for anticancer therapy and a new biomarker for survival prediction in OC.

Expression of integrin α-6 is associated with multi drug resistance and prognosis in ovarian cancer.

Ovarian cancer is a serious threat to women's health. Multidrug resistance is a major cause of post-treatment relapse, metastasis, and even mortality. This characteristic severely restricts the survival of patients with ovarian cancer. Integrin α-6 (ITGA6) is a member of the adhesion molecule family that conducts signals through interactions between the extracellular domain and the matrix, serving important roles in cell adhesion-mediated drug resistance, which is considered to have a critical function in ovarian cancer drug resistance. The association between ITGA6 and ovarian cancer multidrug resistance has been investigated only rarely, to the best of our knowledge. Using RT-qPCR and immunohistochemistry, it was identified that ITGA6 is a central drug resistance gene, and that its expression was upregulated in cisplatin-resistant SKOV3 (SKOV3/DDP2), cisplatin-resistant A2780 (A2780/DDP) cells, and in 54 cases of drug-resistant tissues, as compared with in the controls. Furthermore, bioinformatics and text mining performed by Coremine Medical (http://www.coremine.com/medical/#search) confirmed that ITGA6 was significantly associated with ovarian cancer and drug resistance. Additionally, the high expression of ITGA6 is associated with a poor outcome. The present study provides the basis for further understanding the role of ITGA6 in the regulation of drug resistance in ovarian cancer, and demonstrates that it could be a potential marker for the prognosis of ovarian cancer.

Microarray-based identification of genes associated with prognosis and drug resistance in ovarian cancer.

The outcome for patients with ovarian cancer (OC) is poor because of drug resistance. Therefore, identification of factors that affect drug resistance and prognosis in OC is needed. In the present study, we identified 131 genes significantly dysregulated in 90 platinum-resistant OC tissues compared with 197 sensitive tissues, of which 30 were significantly associated with disease-free survival (DFS; n = 16), overall survival (OS; n = 6), or both (n = 8) in 489 OC patients of the The Cancer Genome Atlas cohort. Of these 30 genes, 17 were significantly upregulated and 13 were downregulated in the 90 resistant tissues, and with one exception, all of the up-/downregulated genes in resistant tissues were predictors of shorter DFS or/and OS. LAX1, MECOM, and PDIA4 were independent risk factors for DFS, and KLF1, SLC7A11, and PDIA4 for OS; combining these genes provided more accurate predictions for DFS and OS than any of the genes used individually. We further verified downregulation of PDIA4 protein in 51 specimens of patients with OC (24 drug resistant's and 27 sensitive's), which confirmed that downregulated PDIA4 predicted DFS and OS. PDIA4 also consistently predicted OS in a larger sample of 1656 patients with OC. These 30 genes, particularly the PDIA4, could be therapeutic targets or biomarkers for managing OC.

Low expression of KCNN3 may affect drug resistance in ovarian cancer.

Drug resistance is a principal contributor to the poor prognosis of ovarian cancer (OC). Therefore, identifying factors that affect drug resistance in OC is critical. In the present study, 51 OC specimens from lab collections were immunohistochemically tested, public data for 489 samples from The Cancer Genome Atlas cohort and 1,656 samples from the Kaplan­Meier Plotter were downloaded, and data were retrieved from Oncomine. It was identified that the mRNA and protein expression of the potassium calcium­activated channel subfamily N member 3 (KCNN3) was markedly lower in OC tissues compared with normal tissues, and in drug­resistant OC tissues compared with sensitive OC tissues. Low KCNN3 expression consistently predicted shorter disease­free and overall survival (OS). Specifically, low KCNN3 expression predicted shorter OS in 395 patients with low expression levels of mucin­16. There was additional evidence that KCNN3 expression is mediated by microRNA­892b. Furthermore, text mining and analyses of protein and gene interactions indicated that KCNN3 affects drug resistance. To the best of the authors' knowledge, this is the first report to associate KCNN3 with poor prognosis and drug resistance in OC. The present findings indicated that KCNN3 is a potential prognostic marker and therapeutic target for OC.

Discovery of microarray-identified genes associated with the progression of cervical intraepithelial neoplasia.

OBJECTIVE: To identify genes potentially associated with cervical intraepithelial neoplasia (CIN) progression through bioinformatic approaches and clinicopathological verification. METHODS: mRNA expression microarray data related to CIN progression were screened from the Gene Expression Omnibus (GEO) database and re-analyzed using bioinformatics approaches. Tissue microarray immunohistochemistry was conducted to assess the significant identified genes in CIN, cervical cancer, and normal tissues. RESULTS: Biological annotation and text mining showed that 14 differentially expressed genes were directly or indirectly related to CIN progression. The expression of 5 up-regulated differentially expressed genes, namely, CCND2, TGFBR2, PRKCB, SH3KBP1 and WNT2B, was examined by tissue microarray immunohistochemistry, with the known CIN progression genes P16 and Ki-67 as the internal reference. Expression of TGFBR2, SH3KBP1, and WNT2B were not detected in CIN and cervical carcinoma, whereas no significant difference in the expression rate of PRKCB was detected (P > 0.05). CCND2, P16, and Ki-67 expression showed a gradual increasing trend in normal, CIN, and cervical cancer. CONCLUSIONS: 14 differentially expressed genes were associated with CIN progression, as indicated by the microarray data analysis results. CCND2 may be a new marker for the prediction of CIN progression in addition to P16 and Ki-67.

Associations of tumor suppressor SPARCL1 with cancer progression and prognosis.

SPARC-like protein 1 (SPARCL1), a member of the family of secreted proteins which is acidic and rich in cysteine, is a potential tumor suppressor gene in most types of tumor. A systemic review and bioinformatics analysis was carried out to determine the associations between SPARCL1 and tumor progression and clinical factors. Downregulation of SPARCL1, thought to be regulated by epigenetic modifications including DNA methylation, serves important functions in tumor progression and development, with its regulatory functions on cell viability, migration, invasion, cell adhesion and drug resistance. Downregulation of SPARCL1 was markedly associated with a poor overall survival rate of patients with one of ≥7 solid tumors and predicted increased mortality in patients with one of ≥4 distinct tumor types. The present review indicated that SPARCL1 may be a therapeutic target for cancer treatment and a biomarker to determine prognosis.

Guangxi cobra venom-derived NGF promotes the osteogenic and therapeutic effects of porous BCP ceramic.

Neuro-osteological interactions have an important role in the regulation of bone metabolism and regeneration. Neuropeptides combined with porous biphasic calcium phosphates (BCP) using protein adsorption may contribute to the acceleration of bone formation. In the present study, we investigated the effect of BCP combined with nerve growth factor (NGF) on the growth of osteoblasts in vitro and the combinational therapeutic effect on the repair of calvarial defects in vivo. NGF was separated and purified from Chinese cobra venom using a simplified three-step chromatography method. BCP combined with NGF exerted a potent effect on osteoblast differentiation, as evidenced by enhanced cell proliferation, increased ALP activity and the up-regulated expression of osteogenesis-related genes and proteins. Further, combinational therapy with BCP and NGF improved calvarial regeneration, which was superior to treatment with therapy alone, as observed using imageological and morphological examination and histological and immunohistochemical staining. The results confirmed the effect of neuro-osteological interactions through combinatorial treatment with NGF and BCP to promote osteogenesis and bone formation, which may provide an effective and economical strategy for clinical application.

Downregulation of miR-429 contributes to the development of drug resistance in epithelial ovarian cancer by targeting ZEB1.

Drug resistance is an obstacle to the treatment of epithelial ovarian cancer. Recently, research has suggested that miRNAs (microRNAs) are involved in cancer development, and speculation has been made about their possible involvement in drug resistance. Thus, we attempted to identify selected miRNAs involved in the development of chemo-resistance in epithelial ovarian cancer. Using miRNA profiles of a panel of cisplatin-resistant (SKOV3/DDP) cells, we validated data using quantitative real time-PCR (QRT-PCR), and studied the effects of miR-429 on cancer cell chemo-sensitivity, using gain- and loss-of-function studies. Data show that SKOV3/DDP expressed less miR-429 compared with parental SKOV3 cells and lower miR-429 expression conferred shorter overall survival (OS) and less progression-free survival (PFS) than the patients with more miR-429 expression (P < 0.01). Upregulation of miR-429 increases cisplatin sensitivity in epithelial ovarian cancer cells. Studies have confirmed that the zinc finger E-box binding homeobox1 (ZEB1) is a direct and functional target of miR-429 and that over-expression of miR-429 reduces autophagy-related protein anti-ATG7, anti-LC3A/B (P < 0.05). Thus, overexpression of miR-429 may suppress ZEB1, and may be a potential sensitizer to cisplatin treatment that may have therapeutic implications.

Cross-validation of genes potentially associated with overall survival and drug resistance in ovarian cancer.

Ovarian cancer is the leading cause of death among malignancies of the female reproductive system. The 5-year survival rates of ovarian cancer (OC) patients are very poor as a result of recurrent disease and emergence of drug resistance; thus, studies to find predictive markers and factors for drug resistance are ongoing. In the present study, based on the microarrays from The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO) profiles covering 1648 OC patients, 11 out of 136 genes that were found to be significantly dysregulated in OC were associated with overall survival (OS) in 489 OC patients of the TCGA cohort. Of these genes, CRISP3, LYVE1, OVGP1 and BCHE were identified as independent prognostic factors, with decreased expression of the first three genes predicting shorter OS, and decreased BCHE predicting longer OS. OVGP1, BCHE and further two genes, CKAP2 and CLDN10, were consistently and remarkably associated with OS when the number of patients increased from 489 to 1583, with increased CKAP2 and decreased CLDN10 predicted shorter OS; combining the four genes provided better predictions. Associations among the four genes with OS in subgroups of OC were further verified. Downregulation of OVGP1 was significantly associated with shorter OS in all subgroups of OC patients, including subgroups of 752 patients treated with chemotherapy regimens containing taxol, 763 with both platin and taxol, 1364 with platin, 371 patients with grade 1-2 disease, 968 with grade 3 disease, 1148 with stage III-IV disease, and 439 with TP53 mutations. In addition, CKAP2 expression was significantly associated with shorter OS in 515 OC patients who had low CA125 levels. Furthermore, comprehensive analyses that including RT-qPCR, bioinformatics analysis and clinical data revealed an association of CKAP2, BCHE, CLDN10 and OVGP1 with drug resistance in OC. The genes identified in the present study might be prognostic factors as well as potential therapeutic targets in the treatment of OC.

STROBE-compliant integrin through focal adhesion involve in cancer stem cell and multidrug resistance of ovarian cancer.

Cancer stem cells (CSCs) are considered to be the root of carcinoma relapse and drug resistance in ovarian cancer. Hunting for the potential CSC genes and explain their functions would be a feasible strategy to meet the challenge of the drug resistance in ovarian cancer. In this study, we performed bioinformatic approaches such as biochip data extraction and pathway enrichment analyses to elucidate the mechanism of the CSC genes in regulation of drug resistance. Potential key genes, integrins, were identified to be related to CSC in addition to their associations with drug resistance and prognosis in ovarian cancer. A total of 36 ovarian CSC genes involved in regulation of drug resistance were summarized, and potential drug resistance-related CSC genes were identified based on 3 independent microarrays retrieved from the Gene Expression Omnibus (GEO) Profiles. Pathway enrichment of CSC genes associated with drug resistance in ovarian cancer indicated that focal adhesion signaling might play important roles in CSC genes-mediated drug resistance. Integrins are members of the adhesion molecules family, and integrin subunit alpha 1, integrin subunit alpha 5, and integrin subunit alpha 6 (ITGA6) were identified as central CSC genes and their expression in side population cells, cisplatin-resistant SKOV3 (SKOV3/DDP2) cells, and cisplatin-resistant A2780 (A2780/DDP) cells were dysregulated as measured by real-time quantitative polymerase chain reaction. The high expression of ITGA6 in 287 ovarian cancer patients of TCGA cohort was significantly associated with poorer progression-free survival. This study provide the basis for further understanding of CSC genes in regulation of drug resistance in ovarian cancer, and integrins could be a potential biomarker for prognosis of ovarian cancer.