Early Prognostic Evaluation Research Articles

The Recent Research Progress of NF-κB Signaling on the Proliferation, Migration, Invasion, Immune Escape and Drug Resistance of Glioblastoma.

Glioblastoma multiforme (GBM) is the most common and invasive primary central nervous system tumor in humans, accounting for approximately 45-50% of all primary brain tumors. How to conduct early diagnosis, targeted intervention, and prognostic evaluation of GBM, in order to improve the survival rate of glioblastoma patients, has always been an urgent clinical problem to be solved. Therefore, a deeper understanding of the molecular mechanisms underlying the occurrence and development of GBM is also needed. Like many other cancers, NF-κB signaling plays a crucial role in tumor growth and therapeutic resistance in GBM. However, the molecular mechanism underlying the high activity of NF-κB in GBM remains to be elucidated. This review aims to identify and summarize the NF-κB signaling involved in the recent pathogenesis of GBM, as well as basic therapy for GBM via NF-κB signaling.

An immune related signature inhibits the occurrence and development of serous ovarian cancer by affecting the abundance of dendritic cells

Serous ovarian cancer is one of the major causes of cancer related death among women worldwide. The advanced diagnosis worsens the prognosis of patients with serous ovarian cancer. The immune system has an important impact on the progression of ovarian cancer. Herein, we aimed to establish an immune related prognostic signature to assist in the early diagnosis, treatment, and prognostic evaluation of patients with serous ovarian cancer. Multiple public data sets and immune related genes were obtained from various online public databases, and immune related prognostic signatures were developed through differential expression analysis, univariate Cox proportional hazard regression analysis, and the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model. The nomogram model, Kaplan–Meier survival curve analysis, receiver operating characteristic (ROC) curve analysis, and decision curve analysis showed that this signature had a good prediction potential. In conclusion, an immune related signature with good prediction efficiency was established through systematic bioinformatics analysis, which may play a tumor inhibition role by affecting the abundance of activated dendritic cells.

Sympathetic skin response (SSR) in pediatric Guillain-Barré syndrome.

In the present study, sympathetic skin response (SSR) characteristics were explored in children with Guillain-Barré syndrome (GBS) and the value of early diagnosis and prognostic evaluation in GBS complicated by autonomic dysfunction (AD) was evaluated. A total of 25 children with GBS and 30 healthy controls (HCs) were enrolled in this prospective study. SSR findings for the two groups were compared. SSR and nerve conduction study (NCS) results were compared among patients with GBS, and differences in clinical characteristics between the groups with abnormal and normal SSR were analyzed. Within the GBS group, six patients (24%) required mechanical ventilation, 17 patients (66.7%) had AD, 18 patients (72%) had an abnormal SSR, and 13 patients (52%) had AD combined with SSR abnormalities. There was a statistically significant difference in SSR latency in the lower limbs between the GBS group and HCs (P < 0.05). There was no statistically significant difference between SSR and NCS results in the acute phase of GBS (P > 0.05), and there was no significant difference in the rate of AD or in Hughes functional grade at nadir between the groups with abnormal and normal SSR (P>0.05). However, there was a statistically significant difference between the results of SSR and NCS tests during the recovery phase (P = 0.003). Abnormal SSR mainly occurred in cases of the acute inflammatory demyelinating polyradiculoneuropathy (AIDP) subtype. In addition, SSR was abnormal in all pediatric GBS patients with poor prognosis 1 month after onset of symptoms. Two-thirds of the children with GBS have AD. SSR could be used for early diagnosis and follow-up of GBS and may also be helpful in evaluating disease severity and short-term prognosis.

Advances in imaging findings of preeclampsia-related reversible posterior leukoencephalopathy syndrome.

Preeclampsia (PE)-related reversible posterior leukoencephalopathy syndrome (RPLS) is a common complication of hypertensive disorders of pregnancy. The syndrome usually occurs after 20 weeks of gestation and can lead to brain injury. Severe headache, seizures, disturbance of consciousness, and other neurological symptoms may occur in severe cases. PE-RPLS has high morbidity and mortality rates and seriously damages maternal and fetal health. In recent years, the continuous advancement of medical imaging technology has provided an important imaging basis for the early diagnosis and prognostic evaluation of RPLS. This article mainly details the research status of the etiology and pathogenesis of PE-RPLS and describes its characteristic imaging findings, especially MRI findings, to provide new insights into its early diagnosis, early treatment, and improvement of prognosis.

An electrochemical immunosensor based on polyaniline microtubules and zinc gallinate for detection of human growth differentiation factor-15.

The incidence rate of cardiovascular diseases (CVDs) remains high, and their mortality rate is significantly higher than that of other diseases. Growth differentiation factor-15 (GDF-15) is a recently developed biomarker for the early diagnosis and prognostic evaluation of CVDs because its concentration in serum increases substantially after a cardiovascular injury or an inflammatory reaction. In this study, a sandwich-type immunosensor was constructed for the sensitive detection of GDF-15. Specifically, peony-like zinc gallinate (ZnGa2O4) prepared using a hydrothermal method, which exhibits excellent electrocatalytic performance, was coupled with Au nanoparticles (NPs) to obtain golden-peony-like ZnGa2O4/Au NPs. Theypreserved the immune activity of GDF-15 antibody molecules and further enhanced the conductivity, thereby realizing additional signal amplification. Hollow polyaniline (PANI) microtubules decorated with Pd NPs were used as the sensing platform (PANI/Pd NPs). The hollow microtubules provided abundant active sites and considerably improved the electron-transfer rate. Under optimal conditions, a linear range and remarkably low detection limit of 100fgmL-1-10ngmL-1 and 42.23fgmL-1, respectively, were achieved. These experimental results indicate that the strategy reported herein can be adopted as a novel approach for the convenient and rapid detection of GDF-15.

Characteristics of sympathetic skin response in children with Guillain-Barré syndrome

To explore the value of sympathetic skin response (SSR) in the early diagnosis and prognostic evaluation of Guillain-Barre syndrome (GBS) in children. A retrospective analysis was conducted on the clinical data of 25 children with GBS who were diagnosed from October 2018 to November 2022, and 30 children who were diagnosed with Tourette's syndrome during the same period were selected as the control group. The characteristics of SSR were compared between the two groups, and the association of SSR with autonomic dysfunction (AD), disease severity, and prognosis was analyzed. The GBS group had a significantly higher abnormal rate of SSR than the control group during the acute phase (P<0.001). SSR combined with early nerve conduction (within 2 weeks after onset) had a sensitivity of 84%, a specificity of 100%, and an accuracy of 93% in the diagnosis of GBS. There were no significant differences in the proportion of AD cases, as well as the Hughes scores during the disease peak, between the abnormal and normal SSR groups (P>0.05). All 7 children with poor short-term prognosis (at 1 month after onset) had abnormal SSR. SSR can be used for the early diagnosis of GBS and the monitoring of treatment response in children.

DNA methylation-based patterns for early diagnostic prediction and prognostic evaluation in colorectal cancer patients with high tumor mutation burden.

Immune checkpoint inhibitor (ICI) therapy has proven to be a promising treatment for colorectal cancer (CRC). We aim to investigate the relationship between DNA methylation and tumor mutation burden (TMB) by integrating genomic and epigenetic profiles to precisely identify clinical benefit populations and to evaluate the effect of ICI therapy. A total of 536 CRC tissues from the Cancer Genome Atlas (TCGA) with mutation data were collected and subjected to calculate TMB. 80 CRC patients with high TMB and paired normal tissues were selected as training sets and developed the diagnostic and prognostic methylation models, respectively. In the validation set, the diagnostic model was validated in our in-house 47 CRC tissues and 122 CRC tissues from the Gene Expression Omnibus (GEO) datasets, respectively. And a total of 38 CRC tissues with high TMB from the COLONOMICS dataset verified the prognostic model. A positive correlation between differential methylation positions and TMB level was observed in TCGA CRC cohort (r=0.45). The diagnostic score that consisted of methylation levels of four genes (ADHFE1, DOK6, GPR75, and MAP3K14-AS1) showed high diagnostic performance in the discovery (AUC=1.000) and two independent validation (AUC=0.946, AUC=0.857) datasets. Additionally, these four genes showed significant positive correlations with NK cells. The prognostic score containing three genes (POU3F3, SYN2, and TMEM178A) had significantly poorer survival in the high-risk TMB samples than those in the low-risk TMB samples (P=0.016). CRC patients with low-risk scores combined with TMB levels represent a favorable survival. By integrating analyses of methylation and mutation data, it is suggested that DNA methylation patterns combined with TMB serve as a novel potential biomarker for early screening in more high-TMB populations and for evaluating the prognostic effect of CRC patients with ICI therapy.

前列腺癌的早期诊断和预后评估的研究进展

前列腺癌的早期诊断和预后评估的研究进展

Non-coding RNAs as potential biomarkers of gallbladder cancer.

Gallbladder cancer (GBC) performs strongly invasive and poor prognosis, and adenocarcinoma is the most common histological type in it. Statistically, the 5-year survival rate of patients with advanced GBC is less than 5%. Such dismal outcome might be caused by chemotherapy resistance and native biology of tumor cells, regardless of emerging therapeutic strategies. Early diagnosis, depending on biomarkers, receptors and secretive proteins, is more important than clinical therapy, guiding the pathologic stage of cancer and the choice of medication. Therefore, it is in urgent need to understand the specific pathogenesis of GBC and strive to find promising novel biomarkers for early screening in GBC. Non-coding RNAs (ncRNAs), especially microRNAs (miRNAs, miRs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are confirmed to participate in and regulate the occurrence and development of GBC. Exceptionally, lncRNAs and circRNAs could act as competing endogenous RNAs (ceRNAs) containing binding sites for miRNAs and crosstalk with miRNAs to target regulatory downstream protein-coding messenger RNAs (mRNAs), thus affecting the expression levels of specific proteins to participate in and regulate the development and progression of GBC. It follows that ncRNAs may become promising biomarkers and potential therapeutic targets for GBC. In this review, we mainly summarize the recent research progress of miRNAs and lncRNAs in regulating the development and progression of GBC, chemoresistance, and predicting the prognosis of patients, and highlight the potential applications of the lncRNA/circRNA-miRNA-mRNA cross-regulatory networks in early diagnosis, chemoresistance, and prognostic evaluation, aiming to better understand the pathogenesis of GBC and develop new diagnostic and therapeutic strategies.

Incorporating higher order network structures to improve miRNA-disease association prediction based on functional modularity.

As microRNAs (miRNAs) are involved in many essential biological processes, their abnormal expressions can serve as biomarkers and prognostic indicators to prevent the development of complex diseases, thus providing accurate early detection and prognostic evaluation. Although a number of computational methods have been proposed to predict miRNA-disease associations (MDAs) for further experimental verification, their performance is limited primarily by the inadequacy of exploiting lower order patterns characterizing known MDAs to identify missing ones from MDA networks. Hence, in this work, we present a novel prediction model, namely HiSCMDA, by incorporating higher order network structures for improved performance of MDA prediction. To this end, HiSCMDA first integrates miRNA similarity network, disease similarity network and MDA network to preserve the advantages of all these networks. After that, it identifies overlapping functional modules from the integrated network by predefining several higher order connectivity patterns of interest. Last, a path-based scoring function is designed to infer potential MDAs based on network paths across related functional modules. HiSCMDA yields the best performance across all datasets and evaluation metrics in the cross-validation and independent validation experiments. Furthermore, in the case studies, 49 and 50 out of the top 50 miRNAs, respectively, predicted for colon neoplasms and lung neoplasms have been validated by well-established databases. Experimental results show that rich higher order organizational structures exposed in the MDA network gain new insight into the MDA prediction based on higher order connectivity patterns.

The World Society of Emergency Surgery Sepsis Severity Score shows no prognostic superiority over the Mannheim Peritonitis Index in patients with complicated intra-abdominal infections

Introduction: Although various scoring systems are already available for early prognostic evaluation of patients with complicated intra-abdominal infections (cIAIs), none has shown the ideal characteristics in everyday practice. In this study, we aimed to find the most reliable prognostic score in patients with cIAIs. Methods: This retrospective study involved 110 patients with cIAIs admitted to the Department of Surgical Diseases at University Hospital, “Prof. Dr. Stoyan Kirkovich” Stara Zagora from January 2017 to July 2019. We compared the prognostic values of Mannheim Peritonitis Index (MPI), World Society of Emergency Surgery Sepsis Severity Score (WSES SSS), quick sequential (sepsis-related) organ failure assessment score (qSOFA), and systemic inflammatory response syndrome (SIRS) using area under receiver operating characteristics (AUROC) curves. Bivariate correlation analysis was used to evaluate the association between scoring systems and the final outcome. Results: The observed in-hospital mortality was 22.7%. Significant correlations were found between MPI and outcome (r = 0.500, p &lt; 0.001), WSES SSS and outcome (r = 0.483, p &lt; 0.001), and qSOFA and outcome (r = 0.356, p &lt; 0.001). Of all the scoring systems, MPI showed the best prognostic performance (AUROC = 0.844, 95% confidence interval (CI) = 0.763–0.924). The identified sensitivity and specificity for MPI cut-off value &gt;25 points were 80% and 77.6%, respectively. Conclusion: The MPI is still one of the best options for prognostic evaluation of patients with cIAIs.

Applications of liquid chromatography-mass spectrometry based metabolomics in predictive and personalized medicine.

Metabolomics is a fast-developing technique used in biomedical researches focusing on pathological mechanism illustration or novel biomarker development for diseases. The ability of simultaneously quantifying thousands of metabolites in samples makes metabolomics a promising technique in predictive or personalized medicine-oriented researches and applications. Liquid chromatography-mass spectrometry is the most widely employed analytical strategy for metabolomics. In this current mini-review, we provide a brief update on the recent developments and novel applications of LC-MS based metabolomics in the predictive and personalized medicine sector, such as early diagnosis, molecular phenotyping or prognostic evaluation. COVID-19 related metabolomic studies are also summarized. We also discuss the prospects of metabolomics in precision medicine-oriented researches, as well as critical issues that need to be addressed when employing metabolomic strategy in clinical applications.

Correlation between serum levels of PTX-3, SIL-2R, inflammatory markers, and APACHE II scores in patients with severe acute pancreatitis.

To investigate the correlation of serum pentraxin 3 (PTX-3), soluble interleukin-2 receptor (SIL-2R), C-reactive protein (CRP), procalcitonin (PCT) levels, and acute physiology and chronic health evaluation II (APACHE II) scores in patients with severe acute pancreatitis (SAP). A total of 30 patients with SAP from October 2020 to October 2021 were selected as the SAP group, and 42 patients with mild acute pancreatitis (MAP) or moderate-severe acute pancreatitis (MSAP) was selected as the control group. The serum levels of PTX-3, SIL-2R, CRP, PCT, and APACHE II scores were evaluated. The serum levels of PTX-3, SIL-2R, CRP, PCT, and APACHE II scores at admission in the SAP group were significantly higher than those in the control group (all P < .05). Spearman analysis showed that serum PTX-3, SIL-2R, CRP, and PCT levels were positively correlated with APACHE II scores (all P < .05). The mortality rate within 28 days was 26.7% in the SAP group; moreover, the serum PTX-3, SIL-2R, CRP, and PCT levels and APACHE II scores at admission in the death group were significantly higher than those in the survival group (all P < .05). The receiver operating curve showed that the combined prediction value of all indicators (PTX-3 + SIL-2R + CRP + PCT + APACHE II) was superior to the single indicators, and the diagnostic sensitivity and specificity were 90.9% and 84.2%, respectively. Serum PTX-3, SIL-2R, CRP, and PCT levels and APACHE II scores have high guiding significance in early diagnosis and prognostic evaluation of SAP patients.

Progress in the application of body fluid and tissue level mRNAs-non-coding RNAs for the early diagnosis and prognostic evaluation of systemic lupus erythematosus.

The diagnosis and differential classification of systemic lupus erythematosus (SLE) is difficult, especially in patients with early-onset SLE who are susceptible to systemic multi-organ damage and serious complications and have difficulties in individualized treatment. At present, diagnosis is based mainly on clinical manifestations and the detection of serological antinuclear antibodies. The pathogenesis of SLE involves multiple factors, is clinically heterogeneous, and lacks specific biomarkers. Therefore, it is necessary to identify new biomarkers for the diagnosis and subtype classification of SLE. Non-coding RNAs (ncRNAs) are composed of microRNAs, long non-coding RNAs, small nucleolar RNAs, circular RNAs, and transfer RNAs. They play an important role in the occurrence and development of diseases and are used widely in the early diagnosis and prognosis of autoimmune diseases. In this review, we focus on the research progress in the diagnosis and prognostic assessment of SLE using humoral to tissue level ncRNAs.

The Application of Liquid Biopsy Techniques in High-Risk Population for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive system and has a 5-year overall survival rate of 14.1%. Many HCC patients are diagnosed at an advanced stage, and thus early screening is essential for reducing the mortality of HCC. In addition to commonly used detection indicators such as serum alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) and abnormal prothrombin (protein induced by vitamin K absence II, PIVKA-II), liquid biopsy techniques have been demonstrated to have diagnostic value in HCC detection. Compared with invasive procedures, liquid biopsy can detect circulatory metabolites of malignant neoplasms. Liquid biopsy techniques can detect circulating tumor cells, circulating tumor DNA, circulating RNA and exosomes and have been used in the early screening, diagnosis and prognostic evaluation of HCC. This paper reviews the molecular biological characteristics and application of different liquid biopsy techniques, and aim to highlight promising biomarkers that may be feasible options for early-stage HCC evaluation to improve early screening in populations at high risk for HCC.

Correlation between Genes of the ceRNA Network and Tumor-Infiltrating Immune Cells and Their Biomarker Screening in Kidney Renal Clear Cell Carcinoma.

This study aimed to using bioinformatics tools, qPCR, and the immunohistochemical analysis to find out factors related to the early diagnosis and prognosis of kidney renal clear cell carcinoma (KIRC). The expression profiles of lncRNA, miRNA, and mRNA of KIRC were downloaded from The Cancer Genome Atlas database. A ceRNA regulatory network was constructed based on the interaction between these three differentially expressed genes. The CIBERSORT deconvolution algorithm was used to analyze the differential distribution of 22 types of immune cells. The Kaplan–Meier survival and Cox analyses were used to screen genes of the ceRNA network and also immune cell subtypes related to the clinical and prognostic prediction of KIRC. Co-expression regulatory relationships were found among LINC01426, LINC00894, CCNA2, L1 cell adhesion molecule (L1CAM), and T follicular helper cells, which served as potential biomarkers. The results of quantitative reverse transcriptase-polymerase chain reaction showed that LINC01426 was upregulated while L1CAM was downregulated in KIRC, but no difference was found in the expression levels of LINC00894 and CCNA2 in cancer and adjacent samples. The immunohistochemical analysis showed that T follicular helper cells were more concentrated in core tissues and metastases of KIRC. In a word, co-expression relationships were found among LINC01426, L1CAM, and T follicular helper cells, and they may serve as biomarkers for early diagnosis and prognostic evaluation of KIRC.

MTUS1 is a promising diagnostic and prognostic biomarker for colorectal cancer

BackgroundThe morbidity and mortality of colorectal cancer (CRC) remain high, posing a serious threat to human life and health. The early diagnosis and prognostic evaluation of CRC are two major challenges in clinical practice. MTUS1 is considered a tumour suppressor and can play an important role in inhibiting cell proliferation, migration, and tumour growth. Moreover, the expression of MTUS1 is decreased in different human cancers, including CRC. However, the biological functions and molecular mechanisms of MTUS1 in CRC remain unclear.MethodsIn the present study, data from The Cancer Genome Atlas (TCGA) database were analysed using R statistical software (version 3.6.3.) to evaluate the expression of MTUS1 in tumour tissues and adjacent normal tissues using public databases such as the TIMER and Oncomine databases. Then, 38 clinical samples were collected, and qPCR was performed to verify MTUS1 expression. We also investigated the relationship between MTUS1 expression and clinicopathological characteristics and elucidated the diagnostic and prognostic value of MTUS1 in CRC. In addition, the correlation between MTUS1 expression and immune infiltration levels was identified using the TIMER and GEPIA databases. Furthermore, we constructed and analysed a PPI network and coexpression modules of MTUS1 to explore its molecular functions and mechanisms.ResultsCRC tissues exhibited lower levels of MTUS1 than normal tissues. The logistic regression analysis indicated that the expression of MTUS1 was associated with N stage, TNM stage, and neoplasm type. Moreover, CRC patients with low MTUS1 expression had poor overall survival (OS). Multivariate analysis revealed that the downregulation of MTUS1 was an independent prognostic factor and was correlated with poor OS in CRC patients. MTUS1 expression had good diagnostic value based on ROC analysis. Furthermore, we identified a group of potential MTUS1-interacting proteins and coexpressed genes. GO and KEGG enrichment analyses showed that MTUS1 was involved in multiple cancer-related signalling pathways. Moreover, the expression of MTUS1 was significantly related to the infiltration levels of multiple cells. Finally, MTUS1 expression was strongly correlated with various immune marker sets.ConclusionsOur results indicated that MTUS1 is a promising biomarker for predicting the diagnosis and prognosis of CRC patients. MTUS1 can also become a new molecular target for tumour immunotherapy.

Expression of serum soluble Klotho protein in patients with renal damage induced by anti-neutrophil cytoplasmic antibody-associated small-vessel vasculitis and influence on prognosis

Abstract Background: Anti-neutrophil cytoplasmic antibody-associated small-vessel vasculitis (AASV) is an autoimmune disease with unclear pathogenesis, which causes damage to multiple organs and systems, renal failure or even death. We aimed to explore the expression of serum soluble Klotho protein in patients with AASV-induced renal damage and influence on prognosis. Methods: A total of 330 AASV patients treated from June 2012 to June 2014 were divided into renal damage and non-renal damage groups. Clinical symptoms and laboratory examination results were compared. They were divided into Klotho &lt;935.05 pg/mL and ≥935.05 pg/mL groups, and renal damage and pathological indices were compared. Survival curves were plotted using Kaplan-Meier method, and 5-year and renal survival rates were compared. Results: Compared with the non-renal damage group, the mean arterial pressure, urine protein and blood creatinine levels significantly rose, while the red blood cell count, hemoglobin, serum albumin, and Klotho protein levels declined in the renal damage group (P&lt;0.05). The optimal cut-off value of Klotho protein in assessing renal damage was 935.05 pg/mL. Compared with Klotho ≥935.05 pg/mL group, the levels of blood creatinine and urine protein significantly increased, and the proportion of normal glomeruli decreased, while that of fibrous crescents rose in Klotho &lt;935.05 pg/mL group (P&lt;0.05). The 5-year renal survival rate was significantly lower in Klotho &lt;935.05 pg/mL group than that in Klotho ≥935.05 pg/mL group (P&lt;0.05). Conclusions: Klotho protein is lowly expressed in patients with renal damage induced by AASV as a potential marker for early diagnosis and prognostic evaluation.

Correlation between dynamic changes in free triiodothyronine levels and 90-day prognosis in patients with HBV-related acute-on-chronic liver failure

BackgroundPatients with HBV-related acute-on-chronic liver failure (HBV–ACLF) have a high 90-day mortality rate, so early prognostic evaluation is important.AimWe aimed to explore the correlation between dynamic changes in free triiodothyronine (FT3) levels and 90-day prognosis of patients with HBV–ACLF.MethodsA prospective cohort study investigated 122 inpatients with HBV–ACLF. Patients were divided into three groups based on the dynamic change in FT3 level, as follows: continuous normal FT3; continuous decreased FT3; and FT3 U-shaped change groups, and patients were divided into survival group and non-survival group according to whether they were alive or not. The correlation between the change in FT3 level and 90-day prognosis was explored. Three factors that affected the prognosis most significantly were used to form an FT3 correlation formula to compare the difference in predicting prognosis between the formula score and the conventional score.ResultsThere were 98 patients with decreased FT3 level (80.33%), and the lowest FT3 level was at 8.52 ± 6.38 days after admission, which lasted for 16 days. There were no significant differences in FT3 levels at admission and at the lowest point between the survival and non-survival groups. Cox regression analysis showed that the FT3 level, FT3 change type, and hepatic encephalopathy (HE) grading were important factors related to prognosis. The area under the receiver operating characteristics curve for the FT3 correlation formula score was 0.892, which was significantly higher than that of the CTP, MELD, MELD–Na, CLIF–SOFA, CLIF–C OF, and AARC scores (P < 0.001).ConclusionsThe FT3 level and its dynamic change type together with the HE grading can facilitate prediction of 90-day prognosis for patients with HBV–ACLF.

Knockdown of lncRNA AL928768.3 inhibits multiple myeloma cell proliferation by inducing cell cycle arrest in G0/G1 phase.

BackgroundMultiple myeloma (MM) is a B-lymphocyte-derived malignancy. It ranks as the second most common hematological malignancy, with relatively high morbidity and mortality. However, the molecular mechanisms of MM occurrence and development remain elusive. This study found that long non-coding RNA AL928768.3 (lncRNA AL) was abnormally expressed in MM samples. However, the effect and molecular mechanism of lncRNA AL on the occurrence and development of MM remains unclear.MethodsBone marrow fluids of MM patients (n=54) and volunteers (n=13) were collected and CD138+ cells were isolated. The expression level of lncRNA AL in MM cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR), and the correlation between the expression level of lncRNA AL and the clinicopathological features of patients was analyzed. Lentiviral vectors targeting lncRNA AL knockdown were constructed and transfected into cells. After transfection, the effects of lncRNA AL knockdown on MM cell proliferation and the cell cycle were detected by the CCK-8 assay, clone formation assay, and flow cytometry. The effect of lncRNA AL knockdown on MM cell cycle-related proteins was detected by Western blot. In addition, tumorigenicity experiments were performed in nude mice to detect the effect of lncRNA AL knockdown on MM cell proliferation in vivo.ResultsLncRNA AL was highly expressed in MM patient samples and cell lines, and was significantly correlated with the disease stage of patients. Knockdown of lncRNA AL significantly inhibited the proliferation and colony formation of MM cells and induced cell cycle arrest in G0/G1 phase. Western blot analysis showed that knockdown of lncRNA AL significantly inhibited the expression of CDK2 and cyclin D1 and promoted the expression of cyclin suppressor p21. Knockdown of lncRNA AL significantly inhibited the proliferation of MM cells in nude mice.ConclusionsLncRNA AL was highly expressed in MM patients. Knockdown of this gene significantly inhibited the proliferative ability of MM cells and induced cell cycle arrest in G0/G1 phase. Therefore, lncRNA AL may be a novel biological target molecule for the early diagnosis, treatment, and prognostic evaluation of MM patients.