Rituximab, but not other biologics, impairs humoral immunity in patients with rheumatoid arthritis-a study using CoVariant protein arrays.

Objectives: RA is an autoimmune disease characterized by chronic inflammation and joint destruction. Biologics are crucial to achieving treat-to-target goals in patients with RA. The global spread and continuous variation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitate the monitoring of variant-specific humoral responses post-vaccination. The aim of this study was to investigate how different biologic treatments for vaccinated RA patients might affect their neutralizing antibodies against multiple SARS-CoV-2 variants. Methods: We recruited RA patients who had received three doses of conventional SARS-CoV-2 vaccines and were treated with various biologics, e.g. TNF inhibitor (etanercept), IL-6 inhibitor (tocilizumab), CTLA4-Ig (abatacept) or anti-CD20 (rituximab). Serum samples were used to profile the binding and neutralizing antibodies using our own SARS-CoV-2 variant (CoVariant) protein array, developed previously. Results: Compared with healthy controls, only RA therapy with rituximab showed a reduction in neutralizing antibodies capable of targeting spike proteins in SARS-CoV-2 wild-type and most variants. This reduction was not observed in binding antibodies against SARS-CoV-2 wild-type or its variants. Conclusion: After receiving three doses of SARS-CoV-2 vaccination, RA patients who underwent rituximab treatment generated sufficient antibodies but exhibited lower neutralizing activities against wild-type and multiple variants, including current Omicron. Other biological DMARDs, e.g. TNF inhibitor, IL-6 inhibitor and CTLA4-Ig, did not show obvious inhibition.

Antibody Profiling of Dengue Severities Using Flavivirus Protein Microarrays.

Dengue is a viral disease transmitted by Aedes aegypti mosquitoes. According to the World Health Organization, about half of the world's population is at risk of dengue. There are four serotypes of the dengue virus. After infection with one serotype, it will be immune to such a serotype. However, subsequent infection with other serotypes will increase the risk of severe outcomes, e.g., dengue hemorrhagic fever, dengue shock syndrome, and even death. Since severe dengue is challenging to predict and lacks molecular markers, we aim to build a multiplexed Flavivirus protein microarray (Flaviarray) that includes all of the common Flaviviruses to profile the humoral immunity and cross-reactivity in the dengue patients with different outcomes. The Flaviarrays we fabricated contained 17 Flavivirus antigens with high reproducibility (R-square = 0.96) and low detection limits (172-214 pg). We collected serums from healthy subjects (n = 36) and dengue patients within 7 days after symptom onset (mild dengue (n = 21), hospitalized nonsevere dengue (n = 29), and severe dengue (n = 36)). After profiling the serum antibodies using Flaviarrays, we found that patients with severe dengue showed higher IgG levels against multiple Flavivirus antigens. With logistic regression, we found groups of markers with high performance in distinguishing dengue patients from healthy controls as well as hospitalized from mild cases (AUC > 0.9). We further reported some single markers that were suitable to separate dengue patients from healthy controls (AUC > 0.9) and hospitalized from mild outcomes (AUC > 0.8). Together, Flaviarray is a valuable tool to profile antibody specificities, uncover novel markers for decision-making, and shed some light on early preventions and treatments.

Developing magnetic barcode bead fluorescence assay for high throughput analyzing humoral responses against multiple SARS-CoV-2 variants.

The continuous mutation of SARS-CoV-2 highlights the need for rapid, cost-effective, and high-throughput detection methods. To better analyze the antibody levels against SARS-CoV-2 and its variants in vaccinated or infected subjects, we developed a multiplex detection named Barcode Bead Fluorescence (BBF) assay. These barcode beads were magnetic, characterized by 2-dimensional edges, highly multiplexed, and could be decrypted with visible light. We conjugated 12 magnetic barcode beads with corresponding nine spike proteins (wild-type, alpha, beta, gamma, delta, and current omicrons), two nucleocapsid proteins (wild-type and omicron), and one negative control. First, the conjugated beads underwent serial quality controls via fluorescence labeling, e.g., reproducibility (R square = 0.99) and detection limits (119 pg via anti-spike antibody). Next, we investigated serums from vaccinated subjects and COVID-19 patients for clinical applications. A significant reduction of antibody levels against all variant beads was observed in both vaccinated and COVID-19 studies. Subjects with two doses of mRNA-1273 exhibited the highest level of antibodies against all spike variants compared to two doses of AZD1222 and unvaccinated. We also found that COVID-19 patients showed higher antibody levels against spike beads from wild-type, alpha, beta, and delta. Finally, the nucleocapsid beads served as markers to distinguish infections from vaccinated subjects. Overall, this study developed the BBF assay for analyzing humoral immune responses, which has the advantages of robustness, automation, scalability, and cost-effectiveness.

Profiling humoral responses to COVID-19 immunization in Kawasaki disease using SARS-CoV-2 variant protein microarrays.

Kawasaki disease (KD) is a form of acute systemic vasculitis syndrome that predominantly occurs in children under the age of 5 years. Its etiology has been postulated due to not only genetic factors but also the presence of foreign antigens or infectious agents. To evaluate possible associations between Kawasaki disease (KD) and COVID-19, we investigated humoral responses of KD patients against S-protein variants with SARS-CoV-2 variant protein microarrays. In this study, plasma from a cohort of KD (N = 90) and non-KD control (non-KD) (N = 69) subjects in categories of unvaccinated-uninfected (pre-pandemic), SARS-CoV-2 infected (10-100 days after infection), and 1-dose, 2-dose, and 3-dose BNT162b2 vaccinated (10-100 days after vaccination) was collected. The principal outcomes were non-KD-KD differences for each category in terms of anti-human/anti-His for binding antibodies and neutralizing percentage for surrogate neutralizing antibodies. Binding antibodies against spikes were lower in the KD subjects with 1-dose of BNT162b2, and mean differences were significant for the P.1 S-protein (non-KD-KD, 3401; 95% CI, 289.0 to 6512; P = 0.0252), B.1.617.2 S-protein (non-KD-KD, 4652; 95% CI, 215.8 to 9087; P = 0.0351) and B.1.617.3 S-protein (non-KD-KD, 4874; 95% CI, 31.41 to 9716; P = 0.0477). Neutralizing antibodies against spikes were higher in the KD subjects with 1-dose of BNT162b2, and mean percentage differences were significant for the 1-dose BNT162b2 B.1.617.3 S-protein (non-KD-KD, -22.89%; 95% CI, -45.08 to -0.6965; P = 0.0399), B.1.1.529 S-protein (non-KD-KD, -25.96%; 95% CI, -50.53 to -1.376; P = 0.0333), BA.2.12.1 S-protein (non-KD-KD, -27.83%; 95% CI, -52.55 to -3.115; P = 0.0195), BA.4 S-protein (non-KD-KD, -28.47%; 95% CI, -53.59 to -3.342; P = 0.0184), and BA.5 S-protein (non-KD-KD, -30.42%; 95% CI, -54.98 to -5.869; P = 0.0077). In conclusion, we have found that KD patients have a comparable immunization response to healthy individuals to SARS-CoV-2 infection and COVID-19 immunization.

Metformin Reprograms Tryptophan Metabolism to Stimulate CD8+ T-cell Function in Colorectal Cancer.

Colorectal carcinogenesis coincides with immune cell dysfunction. Metformin has been reported to play a role in stimulating antitumor immunity, suggesting it could be used to overcome immunosuppression in colorectal cancer. Herein, using single-cell RNA sequencing (scRNA-seq), we showed that metformin remodels the immune landscape of colorectal cancer. In particular, metformin treatment expanded the proportion of CD8+ T cells and potentiated their function. Analysis of the metabolic activities of cells in the colorectal cancer tumor microenvironment (TME) at a single-cell resolution demonstrated that metformin reprogrammed tryptophan metabolism, which was reduced in colorectal cancer cells and increased in CD8+ T cells. Untreated colorectal cancer cells outcompeted CD8+ T cells for tryptophan, leading to impaired CD8+ T-cell function. Metformin in turn reduced tryptophan uptake by colorectal cancer cells, thereby restoring tryptophan availability for CD8+ T cells and increasing their cytotoxicity. Metformin inhibited tryptophan uptake in colorectal cancer cells by downregulating MYC, which led to a reduction in the tryptophan transporter SLC7A5. This work highlights metformin as an essential regulator of T-cell antitumor immunity by reprogramming tryptophan metabolism, suggesting it could be a potential immunotherapeutic strategy for treating colorectal cancer. SIGNIFICANCE: Analysis of the impact of metformin on the colorectal cancer immunometabolic landscape at a single-cell resolution shows that metformin alters cancer cell tryptophan metabolism to stimulate CD8+ T-cell antitumor activity.

Microbiota-derived tryptophan catabolites mediate the chemopreventive effects of statins on colorectal cancer.

Epidemiological studies have indicated an association between statin use and reduced incidence of colorectal cancer (CRC), and work in preclinical models has demonstrated a potential chemopreventive effect. Statins are also associated with reduced dysbiosis in the gut microbiome, yet the role of the gut microbiome in the protective effect of statins in CRC is unclear. Here we validated the chemopreventive role of statins by retrospectively analysing a cohort of patients who underwent colonoscopies. This was confirmed in preclinical models and patient cohorts, and we found that reduced tumour burden was partly due to statin modulation of the gut microbiota. Specifically, the gut commensal Lactobacillus reuteri was increased as a result of increased microbial tryptophan availability in the gut after atorvastatin treatment. Our in vivo studies further revealed that L. reuteri administration suppressed colorectal tumorigenesis via the tryptophan catabolite, indole-3-lactic acid (ILA). ILA exerted anti-tumorigenic effects by downregulating the IL-17 signalling pathway. This microbial metabolite inhibited T helper 17 cell differentiation by targeting the nuclear receptor, RAR-related orphan receptor γt (RORγt). Together, our study provides insights into an anti-cancer mechanism driven by statin use and suggests that interventions with L. reuteri or ILA could complement chemoprevention strategies for CRC.

Profiling Humoral Immunity After Mixing and Matching COVID-19 Vaccines Using SARS-CoV-2 Variant Protein Microarrays.

In November 2022, 68% of the population received at least one dose of COVID-19 vaccines. Owing to the ongoing mutations, especially for the variants of concern (VOCs), it is important to monitor the humoral immune responses after different vaccination strategies. In this study, we developed a SARS-CoV-2 variant protein microarray that contained the spike proteins from the VOCs, e.g., alpha, beta, gamma, delta, and omicron, to quantify the binding antibody and surrogate neutralizing antibody. Plasmas were collected after two doses of matching AZD1222 (AZx2), two doses of matching mRNA-1273 (Mx2), or mixing AZD1222 and mRNA-1273 (AZ+M). The results showed a significant decrease of surrogate neutralizing antibodies against the receptor-binding domain in all VOCs in AZx2 and Mx2 but not AZ+M. A similar but minor reduction pattern of surrogate neutralizing antibodies against the extracellular domain was observed. While Mx2 exhibited a higher surrogate neutralizing level against all VOCs compared with AZx2, AZ+M showed an even higher surrogate neutralizing level in gamma and omicron compared with Mx2. It is worth noting that the binding antibody displayed a low correlation to the surrogate neutralizing antibody (R-square 0.130-0.382). This study delivers insights into humoral immunities, SARS-CoV-2 mutations, and mixing and matching vaccine strategies, which may provide a more effective vaccine strategy especially in preventing omicron.

Intravenous metronidazole-, levofloxacin-containing triple therapy for treating patients with Helicobacter pylori-related active peptic ulcer complications: A pilot study.

OBJECTIVE: The aim of this pilot study was to evaluate the efficacy and safety of intravenous use esomeprazole, metronidazole, and/or levofloxacin in the treatment of Helicobacter pylori (H. pylori)-associated peptic ulcer complications. METHODS: Inpatients with peptic ulcer complications who were not able to take oral medicine were randomly assigned to three groups: triple therapy (esomeprazole, levofloxacin, metronidazole) and dual therapy (esomeprazole, levofloxacin/metronidazole) for 7 days. After intravenous treatment, all patients received open-label oral esomeprazole 20 mg bid for another 1 month. All subjects were followed up for gastroscopy at the seventh day of intravenous treatment to confirm the ulcer healing and 13 C-urea breath test to confirm successful H. pylori eradication 4-6 weeks after completion of oral esomeprazole therapy. RESULTS: The H. pylori eradication rate of both LEV-dual therapy (33.3%, 95% CI: 9.7%-70.0%) and MTZ-dual therapy (50%, 95% CI: 21.5%-78.5%) was significantly lower than that of triple therapy (95%, 95% CI: 71.1%-97.4%) (p = .003, .016). There were no significant differences in the adverse effects among all treatment groups, and the adverse effects were rare. CONCLUSIONS: The intravenous triple regimen, consisting of proton-pump inhibitor, metronidazole, and levofloxacin, could be considered in patients of H. pylori-associated peptic ulcer complications if oral medicine cannot be provided.

Metformin abrogates Fusobacterium nucleatum-induced chemoresistance in colorectal cancer by inhibiting miR-361-5p/sonic hedgehog signaling-regulated stemness.

BACKGROUND: Chemotherapy resistance is the major cause of recurrence in patients with colorectal cancer (CRC). A previous study found that Fusobacterium (F.) nucleatum promoted CRC chemoresistance. Additionally, metformin rescued F. nucleatum-induced tumorigenicity of CRC. Here, we aimed to investigate whether metformin could revert F. nucleatum-induced chemoresistance and explore the mechanism. METHODS: The role of metformin in F. nucleatum-infected CRC cells was confirmed using cell counting kit 8 assays and CRC xenograft mice. Stemness was identified by tumorsphere formation. Bioinformatic analyses were used to explore the regulatory molecules involved in metformin and F. nucleatum-mediated regulation of the sonic hedgehog pathway. RESULTS: We found that metformin abrogated F. nucleatum-promoted CRC resistance to chemotherapy. Furthermore, metformin attenuated F. nucleatum-stimulated stemness by inhibiting sonic hedgehog signaling. Mechanistically, metformin diminished sonic hedgehog signaling proteins by targeting the MYC/miR-361-5p cascade to reverse F. nucleatum-induced stemness, thereby rescuing F. nucleatum-triggered chemoresistance in CRC. CONCLUSIONS: Metformin acts on F. nucleatum-infected CRC via the MYC/miR-361-5p/sonic hedgehog pathway cascade, subsequently reversing stemness and abolishing F. nucleatum-triggered chemoresistance. Our results identified metformin intervention as a potential clinical treatment for patients with chemoresistant CRC with high amounts of F. nucleatum.

Antibody Profiling in COVID-19 Patients with Different Severities by Using Spike Variant Protein Microarrays.

The disease progression of COVID-19 varies from mild to severe, even death. However, the link between COVID-19 severities and humoral immune specificities is not clear. Here, we developed a multiplexed spike variant protein microarray (SVPM) and utilized it for quantifying neutralizing activity, drug screening, and profiling humoral immunity. First, we demonstrated the competition between antispike antibody and ACE2 on SVPM for measuring the neutralizing activity against multiple spike variants. Next, we collected the serums from healthy subjects and COVID-19 patients with different severities and profile the neutralizing activity as well as antibody isotypes. We identified the inhibition of ACE2 binding was stronger against multiple variants in severe compared to mild/moderate or critical patients. Moreover, the serum IgG against nonstructural protein 3 was elevated in severe but not in mild/moderate and critical cases. Finally, we evaluated two ACE2 inhibitors, Ramipril and Perindopril, and found the dose-dependent inhibition of ACE2 binding to all the spike variants except for B.1.617.3. Together, the SVPM and the assay procedures provide a tool for profiling neutralizing antibodies, antibody isotypes, and reagent specificities.

Development of SARS-CoV-2 variant protein microarray for profiling humoral immunity in vaccinated subjects.

SARS-CoV-2 is quickly evolving from wild-type to many variants and spreading around the globe. Since many people have been vaccinated with various types of vaccines, it is crucial to develop a high throughput platform for measuring the antibody responses and surrogate neutralizing activities against multiple SARS-CoV-2 variants. To meet this need, the present study developed a SARS-CoV-2 variant (CoVariant) array which consists of the extracellular domain of spike variants, e.g., wild-type, D614G, B.1.1.7, B.1.351, P.1, B.1.617, B.1.617.1, B.1.617.2, and B.1.617.3. A surrogate virus neutralization on the CoVariant array was established to quantify the bindings of antibody and host receptor ACE2 simultaneously to spike variants. By using a chimeric anti-spike antibody, we demonstrated a broad binding spectrum of antibodies while inhibiting the bindings of ACE2 to spike variants. To monitor the humoral immunities after vaccination, we collected serums from unvaccinated, partial, or fully vaccinated individuals with either mRNA-1273 or AZD1222 (ChAdOx1). The results showed partial vaccination increased the surrogate neutralization against all the mutants while full vaccination boosted the most. Although IgG, IgA, and IgM isotypes correlated with surrogate neutralizing activities, they behave differently throughout the vaccination processes. Overall, this study developed CoVariant arrays and assays for profiling the humoral responses which are useful for immune assessment, vaccine research, and drug development.

CHPF promotes gastric cancer tumorigenesis through the activation of E2F1.

Chondroitin polymerizing factor (CHPF) is an important glycosyltransferase involved in the biosynthesis of chondroitin sulfate. However, the relationship between CHPF and gastric cancer has not been fully investigated. CHPF expression in gastric cancer tissues was detected by immunohistochemistry and correlated with gastric cancer patient prognosis. Cultured gastric cancer cells and human gastric epithelial cell line GES1 were used to investigate the effects of shCHPF and shE2F1 on the development and progression of gastric cancer by MTT, western blotting, flow cytometry analysis of cell apoptosis, colony formation, transwell and gastric cancer xenograft mouse models, in vitro and in vivo. In gastric cancer tissues, CHPF was found to be significantly upregulated, and its expression correlated with tumor infiltration and advanced tumor stage and shorter patient survival in gastric cancer. CHPF may promote gastric cancer development by regulating cell proliferation, colony formation, cell apoptosis and cell migration, while knockdown induced the opposite effects. Moreover, the results from in vivo experiments demonstrated that tumor growth was suppressed by CHPF knockdown. Additionally, E2F1 was identified as a potential downstream target of CHPF in the regulation of gastric cancer, and its knockdown decreased the CHPF-induced promotion of gastric cancer. Mechanistic study revealed that CHPF may regulate E2F1 through affecting UBE2T-mediated E2F1 ubiquitination. This study showed, for the first time, that CHPF is a potential prognostic indicator and tumor promoter in gastric cancer whose function is likely carried out through the regulation of E2F1.

Comparative Analysis of Chemical Constituents in Different Parts of Lotus by UPLC and QToF-MS.

Six parts of lotus (seeds, leaves, plumule, stamens, receptacles and rhizome nodes) are herbal medicines that are listed in the Chinese Pharmacopoeia. Their indications and functions have been confirmed by a long history of clinical practice. To fully understand the material basis of clinical applications, UPLC-QToF-MS combined with the UNIFI platform and multivariate statistical analysis was used in this study. As a result, a total of 171 compounds were detected and characterized from the six parts, and 23 robust biomarkers were discovered. The method can be used as a standard protocol for the direct identification and prediction of the six parts of lotus. Meanwhile, these discoveries are valuable for improving the quality control method of herbal medicines. Most importantly, this was the first time that alkaloids were detected in the stamen, and terpenoids were detected in the cored seed. The stamen is a noteworthy part because it contains the greatest diversity of flavonoids and terpenoids, but research on the stamen is rather limited.

SRSF3 functions as an oncogene in colorectal cancer by regulating the expression of ArhGAP30.

BACKGROUND: Splicing factor SRSF3 is an oncogene and overexpressed in various kinds of cancers, however, the function and mechanism involved in colorectal cancer (CRC) remained unclear. The aim of this study was to explore the relationship between SRSF3 and carcinogenesis and progression of CRC. METHODS: The expression of SRSF3 in CRC tissues was detected by immunohistochemistry. The proliferation and invasion rate was analyzed by CCK-8 assay, colony formation assay, transwell invasion assay and xenograft experiment. The expression of selected genes was detected by western blot or real time PCR. RESULTS: SRSF3 is overexpressed in CRC tissues and its high expression was associated with CRC differentiation, lymph node invasion and AJCC stage. Upregulation of SRSF3 was also associated with shorter overall survival. Knockdown of SRSF3 in CRC cells activated ArhGAP30/Ace-p53 and decreased cell proliferation, migration and survival; while ectopic expression of SRSF3 attenuated ArhGAP30/Ace-p53 and increases cell proliferation, migration and survival. Targeting SRSF3 in xenograft tumors suppressed tumor progression in vivo. CONCLUSIONS: Taken together, our data identify SRSF3 as a regulator for ArhGAP30/Ace-p53 in CRC, and highlight potential prognostic and therapeutic significance of SRSF3 in CRC.

γδ T Cells Promote Steatohepatitis by Orchestrating Innate and Adaptive Immune Programming.

BACKGROUND AND AIMS: The recruitment and activation of inflammatory cells in the liver delineates the transition from hepatic steatosis to steatohepatitis (SH). APPROACH AND RESULTS: We found that in SH, γδT cells are recruited to the liver by C-C chemokine receptor (CCR) 2, CCR5, and nucleotide-binding oligomerization domain-containing protein 2 signaling and are skewed toward an interleukin (IL)-17A+ phenotype in an inducible costimulator (ICOS)/ICOS ligand-dependent manner. γδT cells exhibit a distinct Vγ4+ , PD1+ , Ly6C+ CD44+ phenotype in SH. Moreover, γδT cells up-regulate both CD1d, which is necessary for lipid-based antigens presentation, and the free fatty acid receptor, CD36. γδT cells are stimulated to express IL-17A by palmitic acid and CD1d ligation. Deletion, depletion, and targeted interruption of γδT cell recruitment protects against diet-induced SH and accelerates disease resolution. CONCLUSIONS: We demonstrate that hepatic γδT cells exacerbate SH, independent of IL-17 expression, by mitigating conventional CD4+ T-cell expansion and modulating their inflammatory program by CD1d-dependent vascular endothelial growth factor expression.

Targeting SYK signaling in myeloid cells protects against liver fibrosis and hepatocarcinogenesis.

Liver fibrosis and fibrosis-associated hepatocarcinogenesis are driven by chronic inflammation and are leading causes of morbidity and death worldwide. SYK signaling regulates critical processes in innate and adaptive immunity, as well as parenchymal cells. We discovered high SYK expression in the parenchymal hepatocyte, hepatic stellate cell (HSC), and the inflammatory compartments in the fibrotic liver. We postulated that targeting SYK would mitigate hepatic fibrosis and oncogenic progression. We found that inhibition of SYK with the selective small molecule inhibitors Piceatannol and PRT062607 markedly protected against toxin-induced hepatic fibrosis, associated hepatocellular injury and intra-hepatic inflammation, and hepatocarcinogenesis. SYK inhibition resulted in increased intra-tumoral expression of the p16 and p53 but decreased expression of Bcl-xL and SMAD4. Further, hepatic expression of genes regulating angiogenesis, apoptosis, cell cycle regulation, and cellular senescence were affected by targeting SYK. We found that SYK inhibition mitigated both HSC trans-differentiation and acquisition of an inflammatory phenotype in T cells, B cells, and myeloid cells. However, in vivo experiments employing selective targeted deletion of SYK indicated that only SYK deletion in the myeloid compartment was sufficient to confer protection against fibrogenic progression. Targeting SYK promoted myeloid cell differentiation into hepato-protective TNFαlow CD206hi phenotype downregulating mTOR, IL-8 signaling and oxidative phosphorylation. Collectively, these data suggest that SYK is an attractive target for experimental therapeutics in treating hepatic fibrosis and oncogenesis.

RIP1 Kinase Drives Macrophage-Mediated Adaptive Immune Tolerance in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance and immunotherapeutic resistance. We discovered upregulation of receptor-interacting serine/threonine protein kinase 1 (RIP1) in tumor-associated macrophages (TAMs) in PDA. To study its role in oncogenic progression, we developed a selective small-molecule RIP1 inhibitor with high in vivo exposure. Targeting RIP1 reprogrammed TAMs toward an MHCIIhiTNFα+IFNγ+ immunogenic phenotype in a STAT1-dependent manner. RIP1 inhibition in TAMs resulted in cytotoxic T cell activation and T helper cell differentiation toward a mixed Th1/Th17 phenotype, leading to tumor immunity in mice and in organotypic models of human PDA. Targeting RIP1 synergized with PD1-and inducible co-stimulator-based immunotherapies. Tumor-promoting effects of RIP1 were independent of its co-association with RIP3. Collectively, our work describes RIP1 as a checkpoint kinase governing tumor immunity.

CD24 Overexpression Related to Lymph Node Invasion and Poor Prognosis of Colorectal Cancer.

BACKGROUND: Cluster of differentiation 24 (CD24) has recently been reported as a biomarker for colorectal cancer. However, the clinical and prognostic significance of CD24 in colorectal cancer remains controversial. Therefore, we performed a meta-analysis to clarify this issue. METHODS: A comprehensive literature search was performed using Medline, Embase, Web of Science, and CNKI, and the statistical analysis was conducted using Stata software. RESULTS: A total of thirteen studies including 2,180 cases were included in this meta-analysis. The pooled analysis indicated that CD24 expression was associated with lymph node invasion (RR = 0.71 (negative versus positive), 95% CI = 0.52 - 0.96, p = 0.02, Figure 3), differentiation (RR = 0.81 (well versus poor), 95% CI = 0.67 - 0.99, p = 0.04), and T stage (RR = 0.74 (T1 + T2 versus T3 + T4), 95% CI = 0.65 - 0.85, p = 0.00). The prognosis analysis also suggested CD24 overexpression indicating poorer 5-year OS rate (RR = 0.74, 95% CI = 0.58 - 0.93, p = 0.01) However, CD24 was not associated with other clinicopathological features such as tumor size, tumor grade, distant metastasis, TNM stage and Dukes stage. CONCLUSIONS: Taken together, this meta-analysis suggested that CD24 is an efficient prognostic factor in colorectal cancer.