Mutational landscape of head and neck cancer and cervical cancer in Chinese and Western population.

BACKGROUND: We aimed to unbiasedly map the genetic mutation profile of HNSC and CESC associated with HPV status in the Chinese population (SYSU-cohort) and compare them with Western population (TCGA-cohort). METHODS: Fifty-one HNSC patients (SYSU-HNSC) and 38 CESC patients (SYSU-CESC) were enrolled in this study. Genomic alterations were examined, and the profile was produced using the YuanSuTM450 gene panel (OrigiMed, Shanghai, China). The altered genes were inferred and compared to Western patients from TCGA cohorts. RESULTS: Compared to the TCGA-HNSC cohort, FGFR3 mutation was identified as a novel target in SYSU-HNSC with therapeutic potential. Compared to the TCGA-CESC cohort, some epigenetic regulation-associated genes were frequently mutated in SYSU-CESC cohort (KMT2C, KMT2D, KDM5C, KMT2A). CONCLUSION: In summary, our study provides unbiased insights into the genetic landscape of HNSC and CESC in the Chinese population and highlights potential novel therapeutic targets that may benefit Chinese patients.

Erratum: EPHB4 Regulates the Proliferation and Metastasis of Oral Squamous Cell Carcinoma through the HMGB1/NF-κB Signalling Pathway: Erratum.

[This corrects the article DOI: 10.7150/jca.59331.].

Allergenicity evaluation of five types of commercial food-derived oligopeptide products.

Food-derived oligopeptides are low in molecular weight and have a variety of biological activities. However, many of them are derived from allergens, which may pose a threat to allergic consumers. This study aimed to assess the allergenicity of five types of oligopeptides industrially derived from allergenic foods (soybean, wheat, oyster, salmon skin, and haddock skin). Referring to the decision tree proposed by the FAO/WHO for the allergenicity evaluation of genetically modified food, we included three kinds of bioinformatic tools (AlgPred, AllerCatPro, and AllerTOP), SDS-PAGE, ELISA, cell and animal experiments in this study. The variation of effector levels (IL-4, IFN-γ, His, and mMCP-1) was determined in mouse models. The results revealed that the oligopeptides were all predicted to contain allergenic peptides, of which the soybean one had the highest number of allergenic peptides. Moreover, there were anti-enzymatic peptides present in the soybean oligopeptide. Unexpectedly, the serum IgE binding ability of the peptides was lower than the positive threshold. In addition, no statistical divergence was found between the oligopeptide groups and the control groups in the effector and ß-hexosaminidase levels. Overall, the five types of oligopeptides, though derived from allergens, had low allergenicity.

Sustained antigens delivery using composite microneedles for effective epicutaneous immunotherapy.

Allergen-specific immunotherapy (SIT) is a desirable way of therapy for various allergic diseases such as food allergy (FA). However, frequent visits for more than 3 years and potential adverse effects often hinder patient compliance. Recently, many researchers started focusing on microneedles (MNs) as a new method for SIT. In this study, we proposed an implantable MNs system produced by a two-step casting process, consisting of OVA (antigen)-loaded silk microneedles and a dissolvable, flexible polyvinyl alcohol (PVA) pedestal. Different from PVA, silk fibroin hydrogel has preferable vaccine release ability in vivo and in vitro. Once MNs are inserted into the skin, the PVA pedestal can dissolve in the interstitial fluid of the excised skin within 5 min and implant the OVA-loaded silk microneedle tips in dermal layer as a sustained antigen depot, thus inducing long-lasting immune response for at least 2 weeks. After receiving 3 doses of MN-based immunotherapy, the immune response in OVA-sensitized mice was successfully suppressed, with no apparent side effects. Compared to conventional subcutaneous immunotherapy (total dose of 150 [Formula: see text]g), MN immunotherapy ameliorated systemic anaphylaxis more effectively even at a lower dose (total dose of 30 [Formula: see text]g), demonstrating the antigen dose-sparing potential of the proposed MNs. Moreover, due to the prolonged release effect of silk-PVA composite MNs, the frequency of immunotherapy can be significantly reduced. To sum up, through prolonged skin exposure to antigen, this implantable designed MN may offer a new therapeutic strategy for FA treatment with significant improvements in efficacy and convenience. Schematic illustration of silk-PVA composite microneedles, consisting of OVA (antigen)-loaded silk microneedles and a dissolvable, flexible PVA pedestal. Once inserted into the skin, the PVA pedestal can dissolve in the interstitial fluid of the excised skin within 5 min. Subsequently, the OVA-loaded silk microneedle tips were implanted in the dermal layer as a sustained antigen depot and induced long-lasting immune response. This MNs-based immunotherapy can significantly modulate the Th1/Th2 imbalance of sensitized mice.

Enamel Structure Defects in Kdf1 Missense Mutation Knock-in Mice.

The Keratinocyte differentiation factor 1 (KDF1) is reported to take part in tooth formation in humans, but the dental phenotype of Kdf1 mutant mice has not been understood. Additionally, the role of the KDF1 gene in dental hard tissue development is rarely known. In this study, we constructed a Kdf1 missense mutation knock-in mouse model through CRISPR/Cas9 gene-editing technology. Enamel samples from wildtypes (WT) and Kdf1 homozygous mutants (HO) were examined using micro-computed tomography (micro-CT), scanning electron microscopy (SEM), an atomic force microscope (AFM) and Raman microspectroscopy. The results showed that a novel Kdf1 missense mutation (c. 908G>C, p.R303P) knock-in mice model was constructed successfully. The enamel of HO mice incisors appeared chalky and defective, exposing the rough interior of the inner enamel and dentin. Micro-CT showed that HO mice had lower volume and mineral density in their tooth enamel. In addition, declined thickness was found in the unerupted enamel layer of incisors in the HO mice. Using SEM and AFM, it was found that enamel prisms in HO mice enamel were abnormally and variously shaped with loose decussating crystal arrangement, meanwhile the enamel rods were partially fused and collapsed, accompanied by large gaps. Furthermore, misshapen nanofibrous apatites were disorderly combined with each other. Raman microspectroscopy revealed a compromised degree of order within the crystals in the enamel after the Kdf1 mutation. To conclude, we identified enamel structure defects in the Kdf1 missense mutation knock-in mice, which displayed fragmentary appearance, abnormally shaped prism structure, decreased mineral density, altered crystal ordering degree and chemical composition of the enamel layer. This may support the potential role of the KDF1 gene in the natural development of enamel.

Sialic acid and food allergies: The link between nutrition and immunology.

Food allergies (FA), a major public health problem recognized by the World Health Organization, affect an estimated 3%-10% of adults and 8% of children worldwide. However, effective treatments for FA are still lacking. Recent advances in glycoimmunology have demonstrated the great potential of sialic acids (SAs) in the treatment of FA. SAs are a group of nine-carbon α-ketoacids usually linked to glycoproteins and glycolipids as terminal glycans. They play an essential role in modulating immune responses and may be an effective target for FA intervention. As exogenous food components, sialylated polysaccharides have anti-FA effects. In contrast, as endogenous components, SAs on immunoglobulin E and immune cell surfaces contribute to the pathogenesis of FA. Given the lack of comprehensive information on the effects of SAs on FA, we reviewed the roles of endogenous and exogenous SAs in the pathogenesis and treatment of FA. In addition, we considered the structure-function relationship of SAs to provide a theoretical basis for the development of SA-based FA treatments.

Two Novel Mutations in Ectodysplasin-A Identified in Syndromic Tooth Agenesis.

OBJECTIVE: To discover novel ectodysplasin-A (EDA) and wingless-type MMTV integration site family, member 10A (WNT10A) mutations in tooth agenesis (TA) patients. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Guanghua School of Stomatology, Guangzhou, China, from March 2018 to August 2020. METHODOLOGY: EDA and WNT10A were analysed in eleven TA families by PCR and Sanger sequencing. Bioinformatics and structure modelling analyses were performed after identifying different variants, to predict the resulting conformational alterations in WNT10A and EDA. RESULTS:  Two novel mutations (c.796C>A (p.L266I), c.769G>A (p.G257R)) in EDA and two reported mutations (c.637G>A (p.G213S), c.511C>T (p.R171C))in WNT 10A were detected. Combined with the 3D structural analysis, we discovered a correlation between alterations in hydrogen bond formation and the observed phenotypes, potentially affecting protein binding. CONCLUSIONS: The mutations were predicted to be pathogenic through bioinformatics analyses. In addition, by identifying novel mutations, our knowledge regarding the TA spectrum and tooth development was considerably expanded. KEY WORDS:  Anodontia, EDA, WNT 10A, Whole exome sequencing, Odontogenesis.

Radiographic outcomes and prognostic factors in nonvital immature permanent teeth after apexification with modified calcium hydroxide paste: a retrospective study.

OBJECTIVE: To assess the radiographic outcomes and prognostic factors in nonvital immature permanent teeth after apexification with modified calcium hydroxide paste. MATERIALS AND METHODS: Clinical and radiographic data were collected from 115 necrotic immature permanent teeth (71 caused by trauma and 44 caused by dens evaginatus) treated with apexification using a modified calcium hydroxide. Postoperative root morphology and changes in radiographic root area (RRA) on periapical radiographs were determined and statistically evaluated. Regression analysis was performed to identify factors associated with the outcomes of apexification. RESULTS: The average time for a calcified barrier formation was 10.66 ± 6.37 months. The root morphology after apexification with calcium hydroxide + iodoform paste was similar to that previously described after calcium hydroxide apexification. Compared with the trauma cases, the dens evaginatus cases revealed more type I (40.91% vs 16.9%) and less type II morphology (45.45% vs 67.61%). Although the changes in RRA were limited, the dens evaginatus cases showed greater increment of RRA than the trauma cases (4.12% ± 5.58% vs 0.70% ± 5.21%, P < 0.001). A significant association was found between the preoperative stage of root development and postoperative percentage change in RRA (P < 0.001). CONCLUSIONS: Teeth caused by dens evaginatus had better outcomes after apexification than teeth caused by trauma. Early stages of root development were associated with superior radiographic outcomes. CLINICAL RELEVANCE: Apexification provided reliable outcomes in the treatment of immature teeth with pulp necrosis and apical periodontitis, even though the root development is limited. Treatment decision should be made with comprehensive evaluation of prognostic factors.

COVID19db: a comprehensive database platform to discover potential drugs and targets of COVID-19 at whole transcriptomic scale.

Many open access transcriptomic data of coronavirus disease 2019 (COVID-19) were generated, they have great heterogeneity and are difficult to analyze. To utilize these invaluable data for better understanding of COVID-19, additional software should be developed. Especially for researchers without bioinformatic skills, a user-friendly platform is mandatory. We developed the COVID19db platform (http://hpcc.siat.ac.cn/covid19db & http://www.biomedical-web.com/covid19db) that provides 39 930 drug-target-pathway interactions and 95 COVID-19 related datasets, which include transcriptomes of 4127 human samples across 13 body sites associated with the exposure of 33 microbes and 33 drugs/agents. To facilitate data application, each dataset was standardized and annotated with rich clinical information. The platform further provides 14 different analytical applications to analyze various mechanisms underlying COVID-19. Moreover, the 14 applications enable researchers to customize grouping and setting for different analyses and allow them to perform analyses using their own data. Furthermore, a Drug Discovery tool is designed to identify potential drugs and targets at whole transcriptomic scale. For proof of concept, we used COVID19db and identified multiple potential drugs and targets for COVID-19. In summary, COVID19db provides user-friendly web interfaces to freely analyze, download data, and submit new data for further integration, it can accelerate the identification of effective strategies against COVID-19.

circMine: a comprehensive database to integrate, analyze and visualize human disease-related circRNA transcriptome.

Many circRNA transcriptome data were deposited in public resources, but these data show great heterogeneity. Researchers without bioinformatics skills have difficulty in investigating these invaluable data or their own data. Here, we specifically designed circMine (http://hpcc.siat.ac.cn/circmine and http://www.biomedical-web.com/circmine/) that provides 1 821 448 entries formed by 136 871 circRNAs, 87 diseases and 120 circRNA transcriptome datasets of 1107 samples across 31 human body sites. circMine further provides 13 online analytical functions to comprehensively investigate these datasets to evaluate the clinical and biological significance of circRNA. To improve the data applicability, each dataset was standardized and annotated with relevant clinical information. All of the 13 analytic functions allow users to group samples based on their clinical data and assign different parameters for different analyses, and enable them to perform these analyses using their own circRNA transcriptomes. Moreover, three additional tools were developed in circMine to systematically discover the circRNA-miRNA interaction and circRNA translatability. For example, we systematically discovered five potential translatable circRNAs associated with prostate cancer progression using circMine. In summary, circMine provides user-friendly web interfaces to browse, search, analyze and download data freely, and submit new data for further integration, and it can be an important resource to discover significant circRNA in different diseases.

Association of miR-155 and MIR155HG polymorphisms with cancer risk: A meta-analysis.

BACKGROUND: Analysis of emerging data shows that miRNAs, including miR-155, play important roles in tumorigenesis. Several studies have indicated that miR-155 and MIR155HG polymorphisms may be related to cancer risk, but the association was controversial. Therefore, we conducted this first-reported comprehensive meta-analysis of the association of miR-155 and MIR155HG polymorphisms with cancer risk. MATERIALS AND METHODS: We searched several databases, including PubMed, Embase, and Web of Science, to identify the eligible studies reporting the association of miR-155 and MIR155HG polymorphisms with cancer risk. We calculated the pooled odds ratios (ORs) and 95% confidence intervals (CIs) to analyze the association. Stata software (version 16.0) was used to analyze the data we collected. RESULTS: After being carefully and strictly screened, eight articles reporting on six common single-nucleotide polymorphisms consisting of 6184 cases and 6896 controls were included in this meta-analysis. The six polymorphisms included were rs767649 (T>A), rs928883 (A>G), rs2829803 (G>A), rs1893650 (T>C), rs4143370 (G>C), and rs12482371 (T>C). Our results showed that, in the overall analysis, heterozygotes increased cancer risk, with a marginal P value, compared with wild-type (OR = 1.06, 95% CI = 1.00-1.12, P = 0.062). Subsequent analyses showed that only rs767649 was associated with an increased risk of non-small-cell lung cancer (NSCLC) in an allele model (T vs. A: OR = 1.15, 95% CI = 1.04-1.26, P = 0.007), a homozygote model (TT vs. AA: OR = 1.31, 95% CI = 1.06-1.60, P = 0.011), and a recessive model (TT vs. AT + AA: OR = 1.30, 95% CI = 1.08-1.55, P = 0.005). CONCLUSION: The present meta-analysis indicates that the rs767649 polymorphism might be a potential factor for NSCLC risk; however, more studies should be conducted to confirm these findings.

EPHB4 Regulates the Proliferation and Metastasis of Oral Squamous Cell Carcinoma through the HMGB1/NF-κB Signalling Pathway.

Background: Malignant proliferation and cervical lymphatic metastasis restrict the prognosis of oral squamous cell carcinoma (OSCC). Erythropoietin-producing human hepatocellular B4 (EPHB4) regulates a series of tumour functions involving tumourigenesis, cancer cell attachment and metastasis. However, the mechanism of EphB4 regulating the malignant progression of OSCC has not been fully elucidated. Methods: EPHB4 expression was analysed in 65 OSCC samples and adjacent noncancerous tissues through immunohistochemistry (IHC). siRNA and overexpression plasmids were transfected into OSCC cells to modify EPHB4 expression, and then, regulatory functions were explored in vitro and in vivo. Co-immunoprecipitation (Co-IP) and mass spectrometry were applied to detect proteins interacting with EPHB4. Subsequently, protein stability assays and NF-κB pathway inhibition assays were used to verify the regulation of EPHB4, high-mobility group box 1 (HMGB1) and nuclear factor-κB (NF-κB) activation. Results: EPHB4 was found to be highly expressed in OSCC tissues, which was related to tumour stage and lymphatic metastasis and resulted in a poor prognosis. Cellular experiments and mouse tongue xenograft models further confirmed that high EPHB4 expression promoted the proliferation and metastasis of OSCC tumours. Mechanistically, co-IP and mass spectrometry studies indicated that EPHB4 could bind to HMGB1 and maintain HMGB1 stability. Downregulation of HMGB1 inhibited the proliferation and metastasis of OSCC cells and inhibited NF-κB phosphorylation activation but did not affect EPHB4 expression. Conclusion: This study revealed the mechanism by which EPHB4 promotes the proliferation and metastasis of OSCC by activating the HMGB1-mediated NF-κB signalling pathway, which can be exploited as a novel marker or therapeutic target to control metastasis and improve the survival rate of OSCC.

Selenomethionine-Modified Polyethylenimine-Based Nanoparticles Loaded with miR-132-3p Inhibitor-Biofunctionalized Titanium Implants for Improved Osteointegration.

Titanium and its alloys have been widely used as bone implants, but for reduced treatment span, improvements are urgently needed to achieve faster and better osteointegration. In this study, we found that miR-132-3p inhibited bone-marrow-derived stem cell (BMSC) osteogenic differentiation via targeting BMP2, and that inhibiting miR-132-3p could significantly improve the osteogenic capability of BMSCs. Moreover, we fabricated a biocompatible selenomethionine (SEMET)-modified polyethylene glycol (PEG)/polyethylenimine (PEI) nanoparticle (SeNP) cross-linked with 0.2% gelatin solutions and delivered miR-132-3p inhibitor to biofunctionalize alkali heat-treated titanium implants, resulting in the development of a novel coating for reverse transfection. The biological performances of PEG/PEI/miR-132-3p inhibitor and SeNP/miR-132-3p inhibitor-biofunctionalized titanium were compared. The biological effects, including cell viability, cytotoxicity, adhesion, cellular uptake, and osteogenic capacity of SeNP/miR-132-3p inhibitor-biofunctionalized titanium implants, were then assessed. Results showed that SeNPs presented appropriate morphology, diameter, and positive zeta potential for efficient gene delivery. The transfection efficiency of the SeNP/miR-132-3p inhibitor was comparable to that of the PEG/PEI/miR-132-3p inhibitor, but the former induced less reactive oxygen species (ROS) production and lower apoptosis rates. Confocal laser scanning microscopy (CLSM) demonstrated that SeNP/miR-132-3p inhibitor nanoparticles released from the titanium surfaces and were taken up by adherent BMSCs. In addition, the release profile showed that transfection could obtain a long-lasting silencing effect for more than 2 weeks. The cell viability, cytotoxicity, and cell spreading of SeNP/miRNA-132-3p inhibitor-biofunctionalized titanium were comparable with those of untreated titanium and the SeNP/miRNA-132-3p inhibitor negative control (NC)-biofunctionalized titanium but resulted in higher ALP activity and osteogenic gene expression levels. In vivo animal studies further certified that SeNP/miRNA-132-3p inhibitor nanoparticles from titanium surfaces promoted osteointegration, which was revealed by microcomputed tomography (micro-CT) and histological observations. Taken together, these findings suggested that selenomethionine-modified PEI-based nanoparticles could achieve better biocompatibility. Moreover, titanium implants biofunctionalized by SeNP/miRNA-132-3p inhibitor nanoparticles might have significant clinical potential for more effective osteointegration.

CanImmunother: a manually curated database for identification of cancer immunotherapies associating with biomarkers, targets, and clinical effects.

As immunotherapy is evolving into an essential armamentarium against cancers, numerous translational studies associated with relevant biomarkers, targets, and clinical effects have been reported in recent years. However, a large amount of associated experimental data remains unexplored due to the difficulty in accessibility and utilization. Here, we established a comprehensive high-quality database for cancer immunotherapy called CanImmunother (http://www.biomedical-web.com/cancerit/) through manual curation on 4515 publications. CanImmunother contains 3267 experimentally validated associations between 218 cancer sub-types across 34 body parts and 484 immunotherapies with 642 biomarkers, 108 targets, and 121 control therapies. Each association was manually curated by professional curators, incorporated with valuable annotation and cross references, and assigned with an association score for prioritization. To help clinicians and researchers in identifying and discovering better cancer immunotherapy and their respective biomarkers and targets, CanImmunother offers user-friendly web applications including search, browse, excel table, association prioritization, and network visualization. CanImmunother presents a landscape of experimental cancer immunotherapy association data, serving as a useful resource to improve our insight and to facilitate further discovery of advanced immunotherapy options for cancer patients.

Effect of magnetic graphene oxide on cellular behaviors and osteogenesis under a moderate static magnetic field.

The biological behaviors of magnetic graphene oxide (MGO) in a static magnetic field (SMF) are unknown. The current study is to investigate the cellular behaviors, osteogenesis and the mechanism in BMSCs treated with MGO combined with an SMF. Results showed that the synthetic MGO particles were bio-compatible and could significantly improve the osteogenesis of BMSCs under SMFs, as verified by elevated alkaline phosphatase activity, mineralized nodule formation, and expressions of mRNA and protein levels. Under SMF at the same intensity, the addition of graphene oxide to Fe3O4 could increase the osteogenic ability of BMSCs. The Wnt/ß-catenin pathway was indicated to be related to the MGO-driven osteogenic behavior of the BMSCs under SMF. Taken together, our findings suggested that MGO under an SMF could promote osteogenesis in BMSCs through the Wnt/ß-catenin pathway and hence should attract more attention for practical applications in bone tissue regeneration.

ncRNAVar: A Manually Curated Database for Identification of Noncoding RNA Variants Associated with Human Diseases.

While variants of noncoding RNAs (ncRNAs) have been experimentally validated as a new class of biomarkers and drug targets, the discovery and interpretation of relationships between ncRNA variants and human diseases become important and challenging. Here we present ncRNAVar (http://www.liwzlab.cn/ncrnavar/), the first database that provides association data between validated ncRNA variants and human diseases through manual curation on 2650 publications and computational annotation. ncRNAVar contains 4565 associations between 711 human disease phenotypes and 3112 variants from 2597 ncRNAs. Each association was reviewed by professional curators, incorporated with valuable annotation and cross references, and designated with an association score by our refined score model. ncRNAVar offers web applications including association prioritization, network visualization, and relationship mapping. ncRNAVar, presenting a landscape of ncRNA variants in human diseases and a useful resource for subsequent software development, will improve our insight of relationships between ncRNA variants and human health.

Upregulation of Circular RNA circATRNL1 to Sensitize Oral Squamous Cell Carcinoma to Irradiation.

Accumulating evidence has demonstrated that circular RNAs (circRNAs) play important roles in regulating gene expression involved in tumor development. However, the role of circRNAs in modulating the radiosensitivity of oral squamous cell carcinoma (OSCC) and its potential mechanisms have not been documented. We performed high-throughput RNA sequencing (RNA-seq) to investigate the circRNA expression profile in OSCC patients and discovered that the circATRNL1 expression was significantly downregulated and closely related to tumor progression. The circATRNL1 was structurally validated via Sanger sequencing, RNase R treatment, and specific convergent and divergent primer amplification. Importantly, the expression levels of circATRNL1 decreased after irradiation treatment, and upregulation of circATRNL1 enhanced the radiosensitivity of OSCC through suppressing proliferation and the colony survival fraction, inducing apoptosis and cell-cycle arrest. Moreover, we observed that circATRNL1 could directly bind to microRNA-23a-3p (miR-23a-3p) and relieve inhibition for the target gene PTEN. In addition, the tumor radiosensitivity-promoting effect of circATRNL1 overexpression was blocked by miR-23a-3p in OSCC. Further experiments also showed that PTEN can reverse the inhibitory effect of OSCC radiosensitivity triggered by miR-23a-3p. We concluded that circANTRL1 may function as the sponge of miR-23a-3p to promote PTEN expression and eventually contributes to OSCC radiosensitivity enhancement. This study indicates that circANTRL1 may be a novel therapeutic target to improve the efficiency of radiotherapy in OSCC.

lncRNA CISAL Inhibits BRCA1 Transcription by Forming a Tertiary Structure at Its Promoter.

Cisplatin-based neoadjuvant chemotherapy has been shown to improve survival in patients with squamous cell carcinoma (SCC), but clinical biomarkers to predict chemosensitivity remain elusive. Here, we show the long noncoding RNA (lncRNA) LINC01011, which we termed cisplatin-sensitivity-associated lncRNA (CISAL), controls mitochondrial fission and cisplatin sensitivity by inhibiting BRCA1 transcription in tongue SCC (TSCC) models. Mechanistically, we found CISAL directly binds the BRCA1 promoter and forms an RNA-DNA triplex structure, sequestering BRCA1 transcription factor-GABPA away from the downstream regulatory binding region. Importantly, the clinical relevance of these findings is suggested by the significant association of CISAL and BRCA1 expression levels in TSCC tumors with neoadjuvant chemosensitivity and overall survival. We propose a new model where lncRNAs are tethered at gene promoter by RNA-DNA triplex formation, spatially sequestering transcription factors away from DNA-binding sites. Our study uncovers the potential of CISAL-BRCA1 signaling as a potential target to predict or improve chemosensitivity.