Cluster of differentiation 70 and C-X-C motif chemokine ligand 10 gene expression in vitiligo patients

BackgroundTocilizumab (TCZ), a humanized monoclonal antibody against the interleukin-6 receptor, has been proven to be a safe and effective treatment for rheumatoid arthritis (RA). Because RA is a heterogenous disease and patient response to treatments can vary, identifying characteristics that predict which patients are more likely to respond to TCZ is important for optimal patient care. Serum levels of C-X-C motif chemokine ligand 13 (CXCL13) and soluble intercellular adhesion molecule-1 (sICAM-1) have been associated with response to TCZ in patients with RA.ObjectivesTo evaluate the association of CXCL13 and sICAM-1 with disease activity and response to TCZ in patients with early RA and those with inadequate response to disease-modifying antirheumatic drugs (DMARD-IR).MethodsBaseline and week 24 serum CXCL13 and sICAM-1 levels were measured using available patient samples from the FUNCTION (early RA) and LITHE (DMARD-IR) trials. Correlations between CXCL13 and sICAM-1 levels and Disease Activity Score in 28 joints calculated with erythrocyte sedimentation rate (DAS28-ESR) at baseline and between change in CXCL13 and sICAM-1 and change in DAS28-ESR at week 24 were estimated. CXCL13 and sICAM-1 changes from baseline to week 24 were compared between treatment arms. The effects of TCZ treatment and baseline DAS28-ESR, CXCL13 and sICAM-1 levels on DAS28-ESR remission and 50% improvement per the American College of Rheumatology (ACR50) response at week 24 were determined.ResultsOverall, 458 patients from FUNCTION and 287 patients from LITHE were included. Correlation of baseline serum CXCL13 and sICAM-1 levels with DAS28-ESR was weak to moderate. CXCL13 and sICAM-1 levels decreased significantly at week 24 in TCZ-treated patients in both the early-RA and DMARD-IR populations. CXCL13 and sICAM-1 changes correlated moderately to weakly with DAS28-ESR changes at week 24 in both populations. The treatment regimen, but not baseline CXCL13 and sICAM-1 levels, had a significant effect on the likelihood of DAS28-ESR remission and ACR50 response.ConclusionsAlthough CXCL13 and sICAM-1 are modestly associated with RA disease activity, they do not predict response to TCZ in all RA populations.

Background Our knowledge of the pathophysiology of vitiligo has advanced significantly. However, there are still some unclear aspects. Chemokine C-X-C motif ligand 10 (CXCL10) is a biomarker of vitiligo activity and chemokine C–C motif ligand 8 (CCL8) is a chemokine that has been studied recently in vitiligo pathogenesis. Objective The primary objective was to compare the efficacy and safety of adding low-dose simvastatin to narrowband ultraviolet B (NB-UVB) versus NB-UVB monotherapy for vitiligo treatment including the effect on CXCL10 and CCL8. The secondary objective was to look for any potential links between CCL8 and vitiligo. Patients and methods In this interventional comparative study 50 vitiligo patients were enlisted and randomly split into two groups: the treatment group received NB-UVB plus simvastatin, while the control group received NB-UVB alone for 3 months. Enzyme-linked immunosorbent assay kits were used to test the serum levels of CXCL10 and CCL8, and the vitiligo area scoring index (VASI) score was computed both before and after therapy. Results Following treatment, the median values of the VASI score reduction were considerably higher (P=0.037) in the treatment group (1.50) in comparison with controls (0.52). In addition, the median serum levels of CXCL10 and CCL8 were significantly lower (P=0.003 and 0.030, respectively) in the treatment group (132.6 and 110.8 ng/l, respectively) than in the control group (155 and 122.8 ng/l, respectively). There were no side effects noted. CCL8 and CXCL10 serum levels had a positive correlation. Conclusion The outcomes of the therapy point to the potential for simvastatin to work in conjunction with NB-UVB to treat vitiligo. Current findings also suggest that CCL8 may play a role in the pathogenesis of vitiligo. In this study, CXCL10 is not correlated with disease severity.

C-X-C motif chemokine ligand 5 (CXCL5) is a CXC-type chemokine that is a crucial inflammatory mediator and a powerful attractant for granulocytic immune cells. Increasing evidence has indicated that CXCL5 is involved in the tumorigenesis of various malignancies. The present investigation demonstrated that CXCL5 was expressed in both hepatoblastoma HepG2 cells and liver stellate LX-2 cells, and CXCL5's receptor C-X-C chemokine receptor type 2 (CXCR2) was expressed in HepG2 cells by reverse transcription-polymerase chain reaction (RT-PCR), western blotting and ELISA assays. Cell counting kit-8, colony formation and Transwell assays revealed that exogenous CXCL5 expression efficiently promoted proliferation, colony formation and migration of HepG2 cells. To explore the autocrine and paracrine roles of CXCL5 in the oncogenic potential of HepG2 cells, HepG2 cells overexpressing CXCL5 and LX-2 cells overexpressing CXCL5 were successfully constructed by gene transfection. Similarly, overexpression of CXCL5 in HepG2 also enhanced proliferation, colony formation and migration of HepG2 cells. Furthermore, the condition medium of LX-2 cells overexpressing CXCL5 affected the proliferation and migration of HepG2 cells. RT-PCR and western blotting assays were also conducted to explore whether overexpression of CXCL5 in HepG2 modulated the expression of genes. The results revealed that overexpression of CXCL5 regulated the expression of several genes, including N-myc downregulated gene 3,w B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein, P53, vascular endothelial growth factor, interleukin (IL)-18, IL-1β and cystathionine-γ-lyase. In conclusion, the present findings indicate that CXCL5/CXCR2 axis contributes to the oncogenic potential of hepatoblastoma via autocrine or paracrine pathways by regulating expression of genes associated with the progression of carcinoma.

Introduction/Background Ruxolitinib cream is a topical formulation of the selective Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib and is the first and only repigmentation treatment approved by the US Food and Drug Administration and European Commission for nonsegmental vitiligo in patients ≥12 years old. Objectives To evaluate treatment-associated changes in biomarkers among patients with vitiligo, correlate changes in key biomarkers with efficacy, and assess the safety and tolerability of ruxolitinib cream. Methods The phase 2, randomized, double-blind, vehicle-controlled TRuE-V mechanism of action study (NCT04896385) was conducted in adult patients (≥18 years) with vitiligo ≤50% of total body surface area. Patients were randomized 2:1 to twice-daily 1.5% ruxolitinib cream or vehicle cream for 24 weeks, after which all patients could apply 1.5% ruxolitinib cream through Week 52. Changes from baseline in local and systemic immune biomarkers, including C-X-C motif chemokine ligand 10 (CXCL10), were evaluated at Weeks 4, 12, and 24. The relative expression of >3000 serum protein analytes was assessed using the Olink Explore platform, and a validated Meso Scale Discovery (MSD) assay was used to confirm absolute levels of serum CXCL10. Relative CXCL10 expression was determined by quantitative polymerase chain reaction (qPCR) from isolated biopsy samples. Punch biopsies (2.5 mm) were taken from lesional and nonlesional skin at baseline and lesional skin (even if the lesion had cleared) at Weeks 12, 24, and 40. Treatment efficacy was determined by the percentage change from baseline in facial and total Vitiligo Area Scoring Index (F-VASI and T-VASI, respectively). Safety was evaluated by the frequency and severity of adverse events. Results The study enrolled 60 patients (ruxolitinib cream, n=41; vehicle, n=19). Patients’ mean (SD) age was 44.7 (12.8) years, 56.7% were male, and 53.3% had lighter skin (Fitzpatrick skin types I–III). At baseline, patients had a median (range) disease duration of 12.0 (0.1–52.9) years and mean (SD) F-VASI and T-VASI scores of 1.1 (0.6) and 12.1 (9.4), respectively. Olink Explore identified few differentially expressed proteins in patient sera (adjusted P<0.05 and log2 fold change >1.25), including CXCL10, SH2D1A, and granzyme B. As early as Week 12, serum CXCL10 levels (in MSD assay) were significantly reduced in ruxolitinib cream–treated patients compared with baseline. Skin CXCL10 levels were similar in lesional and nonlesional skin at baseline but were significantly lowered in lesional skin at Week 12 with ruxolitinib cream. In ruxolitinib cream–treated patients, significant mean [SD] percentage reductions from baseline were seen in F-VASI scores at Week 12 (–32.9 [33.6]) and in T-VASI scores at Week 24 (–21.2 [18.5]). Further, T-VASI scores significantly correlated with a change in serum CXCL10 levels between baseline and Week 24. Most systemic proteins did not correlate or only weakly correlated with F-VASI and T-VASI scores. Through Week 24, 46.3% of 41 patients who applied ruxolitinib cream reported treatment-emergent adverse events (none serious), the most common being COVID-19 (9.8%), application site acne (4.9%), and application site rash (4.9%). Conclusions Taken together, these data are consistent with the role of the interferon-gamma:CXCL10 axis as a central mediator of vitiligo pathogenesis. Serum CXCL10 levels decreased significantly in patients who applied ruxolitinib cream, which correlated with improvement in T-VASI scores. Additionally, skin CXCL10 levels were significantly reduced after 12 weeks of ruxolitinib cream treatment.

Introduction: C-X-C motif chemokine ligand 1 (CXCL1) is a potent neutrophil chemoattractant that plays a pivotal role in recruiting neutrophils during inflammatory conditions. This study explored the role of CXCL1 in modulating the gut microbiota, influencing neutrophil infiltration, and contributing to the development of colitis. Methods: We employed quantitative PCR to assess CXCL1 expression in colon samples. A mouse model of dextran sulfate sodium (DSS)-induced colitis was utilized to explore the progression of colitis in wild-type (WT) and CXCL1-deficient (CXCL1−/−) mice. Results: Colitis attenuation was evident in CXCL1−/− mice. Significant alterations were observed in the gut microbiome, as revealed by 16S rRNA gene sequencing. Furthermore, CXCL1−/− mice exhibited reduced gut permeability and diminished endotoxin levels in peripheral blood following DSS treatment compared to WT mice. In response to DSS treatment, WT mice showed a clear increase in neutrophil infiltration, while CXCL1−/− mice exhibited lower levels of infiltration. Fecal microbiota transplantation (FMT) using stools from CXCL1−/− mice alleviated DSS-induced colitis. Interestingly, FMT from patients with colitis increased CXCL1 and Ly6G expression in the colons of gut-sterilized mice. Clinical data analysis revealed elevated CXCL1 and CD15 expression in patients with colitis, with a positive correlation between the severity of colitis and the expression of CXCL1 and CD15. Conclusion: These findings shed light on the pivotal role of CXCL1 in promoting colitis by modulating the gut microbiota.

ObjectiveThe biological significance of the chemokine ligand C-X-C motif chemokine ligand 13 (CXCL13) may play a significant role in the pathogenesis of uterine corpus endometrial carcinoma (UCEC). This study aims to identify and verify CXCL13 with predictive value for prognosis in UCEC.MethodsCXCL13 mRNA expression differences were analyzed using R software in three independent datasets: one each from The Cancer Genome Atlas (TCGA) and two from the Gene Expression Omnibus (GEO), namely GSE17025 and GSE106191. The correlation between CXCL13 expression and prognosis was evaluated by Kaplan–Meier analysis. Univariate and multivariate Cox analyses were utilized to construct a prognostic nomogram. Tumor Immune Estimation Resource (TIMER) and the Tumor and Immune System Interaction Database (TISIDB) were employed to assess the relationship between CXCL13 and tumor immune infiltration. Coexpressed genes with CXCL13 were identified by the Spearman correlation analysis. A CXCL13 protein–protein interaction (PPI) network was constructed with the STRING website tool and hub genes were screened out. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analyses were performed with the “clusterProfiler” R package. Gene set enrichment analysis (GSEA) was used to identify underlying biological mechanisms. A drug-gene interaction network was constructed in the Comparative Toxicogenomics Database (CTD).ResultsHigh CXCL13 mRNA expression were validated in UCEC in the above three independent datasets. High CXCL13 expression was associated with favorable prognosis in UCEC. A nomogram for predicting the 1-, 3-, and 5-year survival probability in UCEC was construct based on CXCL13 expression and other clinical parameters. The use of Spearman correlation indicated certain correlation between CXCL13 and immune cells and immune checkpoint (ICP) genes. Seven hub genes were upregulated in UCEC, namely CXCL9, IFNG, CXCL10, CXCL11, GBP5, CCL18, and GZMB. The expression and prognostic relevance of CXCL9, IFNG, GBP5, and GZMB were in accordance with CXCL13. The main biological processes enriched were cytokine-cytokine receptor interaction and chemokine signaling pathway.ConclusionsThe above comprehensive analyses suggest that CXCL13 may serve as a potential prognostic biomarker for UCEC, specifically for early-stage UCEC.

Background Serum levels of C-X-C motif chemokine ligand 13 (CXCL13) and soluble intercellular adhesion molecule-1 (sICAM-1) have been associated with response to tocilizumab (TCZ) in patients with rheumatoid arthritis (RA); levels of matrix metalloproteinase-3 (MMP-3) and S100A8/A9 have also been associated with RA disease activity and joint damage. Objectives To evaluate the association of CXCL13, sICAM-1, MMP-3 and s100A8/A9 levels with disease activity and response to TCZ in patients with RA who achieved low disease activity with 24 weeks of TCZ + methotrexate (MTX) treatment and were subsequently randomized to TCZ monotherapy (mono) or TCZ + MTX in the COMP-ACT trial (NCT01855789). Methods US patients with RA who had an inadequate response to MTX received initial combination therapy of MTX plus TCZ 162 mg subcutaneous for 24 weeks. Patients who achieved Disease Activity Score in 28 joints calculated with erythrocyte sedimentation rate (DAS28-ESR) ≤ 3.2 at Week 24 were randomized 1:1 (double-blind) to receive either TCZ mono or continue TCZ + MTX until Week 52. Randomized patients were included in the present study based on baseline, Week 24 and Week 40 sample availability; serum levels of CXCL13, sICAM-1, MMP-3 and S100A8/A9 were measured by immunoassay. Correlations between CXCL13, sICAM-1, MMP-3 and S100A8/A9 levels and DAS28-ESR at baseline, Week 24 and Week 40 were determined according to Spearman correlation coefficient. Changes in CXCL13, sICAM-1, MMP-3 and S100A8/A9 levels from baseline to Week 24 (open-label period) were determined using Wilcoxon test. Mean changes in CXCL13, sICAM-1, MMP-3 and S100A8/A9 levels from Week 24 to Week 40 (randomized period) were compared between treatment arms using analysis of covariance. Results Of 296 randomized patients, 249 were included (TCZ mono, n = 126; TCZ + MTX, n = 123). Biomarker levels were well balanced across treatment arms at baseline and Week 24 (randomization). At baseline, there were weak to mild correlations between DAS28-ESR and biomarker levels (CXCL13 [r = 0.13, P = 0.0411], sICAM-1 [r = 0.20, P = 0.0015], MMP-3 [r = 0.19, P = 0.0021], S100A8/A9 [r = 0.25, P = 0.0001]). Significant reductions in mean biomarker levels were observed from baseline to Week 24 (open-label period) among the total randomized patients (P Conclusion In agreement with previous studies, the association between baseline disease activity and CXCL13, sICAM-1, MMP-3 and S100A8/A9 levels was weak to mild; TCZ + MTX treatment from baseline to Week 24 (open-label period) resulted in significant reductions in all biomarkers. Changes in levels of CXCL13, sICAM-1, MMP-3 and S100A8/A9 from Week 24 to 40 (randomized period) were similar between treatment groups, consistent with the finding of non-inferiority of TCZ mono compared with TCZ + MTX in patients with RA who achieve low disease activity with TCZ + MTX. Acknowledgement This study was funded by Genentech, Inc. Disclosure of Interests D. James Haddon Shareholder of: Stockholder of Genentech/Roche, Employee of: Employee of Genentech/Roche, Thierry Sornasse Employee of: Genentech, Inc., Michael J. Townsend Shareholder of: Stockholder of Genentech/Roche, Employee of: Genentech/Roche, Jinglan Pei Employee of: Genentech, Margaret Michalska Employee of: Genentech, Inc.

SummaryBackgroundSystemic sclerosis-interstitial lung disease (SSc-ILD) is the leading cause of death in patients with SSc. There is an unmet need for predictive biomarkers to identify patients with SSc at risk of ILD. Previous studies have shown that interferon (IFN) pathways may play a role in SSc. We assessed the use of C-X-C motif chemokine ligand 10 (CXCL10) as a predictive biomarker for new onset of ILD in patients with SSc.MethodsOne-hundred-sixty-five (Female, N = 130) patients with SSc (SSc-ILD, N = 41) and 13 (Female, N = 8) healthy controls were investigated retrospectively. CXCL10 protein levels were measured by ELISA. We performed log rank analysis with baseline CXCL10 serum levels. CXCL10 nanoString data from lung tissues obtained from transplanted patients with SSc-ILD were extracted. Fifteen (Female, N = 10) patients with SSc (SSc-ILD, N = 7) were recruited for bronchoalveolar lavage (BAL) procedure. Lung fibroblasts were treated with BAL-fluid or serum from patients with SSc with or without ILD. Inflammatory/fibrotic genes were assessed.FindingsSerum CXCL10 levels were higher in patients with SSc-ILD compared to SSc patients without ILD [Median (IQR):126 pg/ml (66–282.5) vs. 78.5 pg/ml (50–122), P = 0.029, 95% CI: 1.5 × 10−6 to 0.4284]. Survival analysis showed that baseline CXCL10 levels >78.5 pg/ml have a 2.74-fold increased risk of developing new onset of ILD (Log-rank: P = 0.119) on follow-up. CXCL10 levels in BAL supernatant were not different in patients with SSc-ILD compared to SSc without ILD [76.1 pg/ml (7.2–120.8) vs. 22.3 pg/ml (12.1–43.7), P = 0.24, 95% CI: −19.5 to 100]. NanoString showed that CXCL10 mRNA expression was higher in inflammatory compared to fibrotic lung tissues [4.7 (4.2–5.6) vs. 4.3 (3.6–4.7), P = 0.029]. Fibroblasts treated with SSc-ILD serum or BAL fluids overexpressed CXCL10.InterpretationsClinical, transcriptomic, and in vitro data showed that CXCL10 is potentially involved in early SSc-ILD. More research is needed to confirm whether CXCL10 can be classified as a prospective biomarker to detect patients with SSc at higher risk of developing new onset ILD.FundingThis collaborative project is co-financed by the 10.13039/501100016238Ministry of Economic Affairs and Climate Policy of the Netherlands utilizing the PPP-allowance made available by the 10.13039/100016036Top Sector Life Sciences & Health to stimulate public-private partnerships (PPP-2019_007). Part of this study is financially supported by 10.13039/100013995Sanofi Genzyme (NL8921).

Chemokines have been demonstrated to serve an important role in a variety of diseases, particularly in tumor progression. There have been numerous studies that have reported that T cells serve major roles in tumor progression. However, the function of CXC motif chemokine ligand 9 (CXCL9) in prostate cancer remains unknown. The present study aimed to investigate the role of CXCL9 in prostate cancer. A prostate cancer mouse model was generated by treating C57/BL-6 and B6.Cg-Selplgtm1Fur/J mice with 3,2′-dimethyl 4-aminobiphenyl (DMAB). Hematoxylin and eosin staining detected the histopathological alterations of mouse prostate tissues. Immunohistochemistry (IHC) staining determined cell proliferation of the mice. Flow cytometry was used to detect the alterations of T cells in C57+DMAB or CXCL9+DMAB mice. Immunofluorescence revealed that there was positive expression of interleukin-6 (IL-6) and transforming growth factor (TGF)-β in the mouse tissues. The survival rates of C57+DMAB and CXCL9+DMAB mice was analyzed. The association of CXCL9 expression and clinical stages was also evaluated. Results revealed that prostate cancer pathology and cell proliferation in CXCL9+DMAB mice were significantly greater compared with the C57+DMAB mice. Compared with C57+DMAB mice, the number of T cells in peripheral blood and spleen of CXCL9+DMAB mice was significantly reduced. IHC demonstrated that the expression of IL-6 and TGF-β was significantly downregulated in the CXCL9+DMAB mice. The survival rate of CXCL9+DMAB mice was significantly decreased compared with the C57+DMAB mice. In addition, reverse transcription-quantitative polymerase chain reaction analysis demonstrated that CXCL9 mRNA expression in clinical samples was positively associated with clinical pathological stages of prostate cancer. In conclusion, CXCL9 may promote prostate cancer progression via inhibition of cytokines from T cells.

The implementation of novel blood-based biomarkers is desired to reduce the diagnostic delay and burden for myositis patients. In this retrospective study, the potential of C-X-C motif chemokine ligand 10 (CXCL10) and growth differentiation factor 15 (GDF15) was explored in an established patient cohort diagnosed with immune-mediated necrotizing myopathy (IMNM; n = 21), sporadic inclusion body myositis (IBM; n = 18), overlap myositis (OM; n = 3), dermatomyositis (DM; n = 2), and anti-synthetase syndrome (ASS; n = 1), comparing these results with healthy controls (n = 10) and patients with a hereditary neuromuscular disorder (n = 14). CXCL10 and GDF15 were quantified in sera with enzyme-linked immunosorbent assays and immunolocalized in skeletal muscle tissue. In myositis patients, serum CXCL10 levels were significantly increased 9.6-fold compared to healthy controls and 4.2-fold compared to disease controls. Mean levels of CXCL10 were 929 ± 658 pg/mL of serum in IBM and 425 ± 324 pg/mL of serum in IMNM. With the threshold set to 180 pg/mL of CXCL10, myositis patients could be differentiated from healthy and disease controls with a sensitivity of 0.80 and a specificity of 0.71. Incorporating a threshold of 300 pg/mL for GDF15 reduced false negatives to two IMNM patients only. Subsets of muscle-infiltrating immune cells expressed CXCL10, and serum levels correlated with muscle inflammation grade. We propose adding circulating CXCL10 and GDF15 to the blood-based diagnostic toolkit for myositis as a valuable patient-friendly approach.

Introduction: Lung cancer is one of the most common cancers with high mortality rate because of the late diagnosis. The present study aimed to quantitatively measure the C-X-C Motif Chemokine Ligand 5 ( CXCL5 ) gene expression level in tissue samples of lung cancer patients to investigate its value as a biomarker during lung cancer diagnosis and screening. Materials and Methods: Tissue samples were collected from 30 patients. Total RNA was extracted from tumor and normal tissues of patients. The rate of CXCL5 gene expression was initially measured in A549 cell line and next, the expression level of this gene in tumor tissue samples of patients suffering from Non-Small Cell Lung Cancer was compared to the normal lung tissue of the same patients. Results: The results demonstrated significant increase of CXCL5 gene expression in cancer samples compared to normal tissues of the same samples. The increase was 5.8 fold for cancerous tissues in comparison with normal tissues (P=0.03). There was no difference between the tumor type (adenocarcinoma, squamous cell carcinoma) and average CXCL5 gene expression rate (P=0.09). In cancerous samples, the expression level of CXCL5 was higher in men compared with those of women (P=0.04). There was no relationship between the change of gene expression and the age of the patients (p=0.08). Conclusion: Based on the results, it can be concluded that the quantitative expression level of CXCL5 in lung cancer patients could be used as a biomarker to screen lung cancer samples, regardless of age of patients and tumor type. However, it can discriminate the stage of tumor.

Systemic lupus erythematosus (SLE) is characterized by a type I interferon (IFN) signature, and traditional methods for its measurement like gene expression analysis are cumbersome for routine use. Thus, we aimed to study galectin-9 as a biomarker and compared it with a validated marker, C-X-C motifchemokine ligand 10(CXCL-10). Ninety-seven patients with SLE (26 years; 89 females) were included and stratified based on renal involvement and activity into - active (SLEDAI > 4) renal (35), active non-renal (32) and inactive renal subgroups (30) along with 20 healthy controls (HC, 25 years; 15 females). The median disease duration was 24months (6-48), and SLEDAI 2K was 9 (2-15). Serum and urine galectin-9 and CXCL-10 levels were measured by ELISA. Urine levels were normalized with spot urine creatinine values. Follow-up serum and urine galectin-9 levels were measured for those in the active renal group at 6months. Patients with SLE had higher serum galectin-9 (5.6 vs 1.7 μg/mL, p = .0001) but not urine galectin-9 (0.52 vs 0.32 μg, p = .7) levels as compared to HC. Serum galectin-9 but not urine galectin-9 was higher in patients with active as compared to inactive lupus (12.9 - active renal, 16.7 - active non-renal vs 3.57 μg/mL, p = .04 and .005). Serum CXCL-10 (0.16 vs 0.05, p = .01) and urine CXCL-10 (0 vs 0, p = .01) were both significantly higher in the SLE group as compared with HC. Serum but not urine CXCL-10 was higher in the active as compared to inactive lupus (0.2 - active renal, 0.3 - active non-renal vs 0.08 μg/mL, p = .9 and .02). Serum galectin-9 showed a modest correlation with CXCL-10 0.4 (0.2-0.6), whereas none was found between their urine levels.Serum galectin-9 and CXCL-10 showed a moderate positive correlation with SLEDAI 2K. Serum galectin-9 showed a greater AUC than CXCL-10 (0.77 vs 0.67) in differentiating active from inactive SLE, and both tested together had the best AUC of 0.82. However, urinary levels had no association with SLEDAI 2K or renal SLEDAI. In a subset of patients with active renal disease, serum galectin-9 but not urine levels declined significantly after 6months. Serum galectin-9 is a good marker of lupus activity; however, it does not differentiate between active renal and active non-renal disease. It performs slightly better than CXCL-10. Urinary galectin-9 does not reflect renal activity.

The C-X-C motif chemokine ligand-9 (CXCL9) is related to the progression of multiple neoplasms. Yet, its biological functions in uterine corpus endometrioid carcinoma (UCEC) remain shrouded in confusion. Here, we assessed the prognostic significance and potential mechanism of CXCL9 in UCEC. Firstly, bioinformatics analysis of the public cancer database, including the Cancer Genome Atlas / the Genotype-Tissue Expression project (TCGA+ GTEx, n=552) and Gene Expression Omnibus (GEO): GSE63678 (n=7), were utilized for the CXCL9 expression-related analysis in UCEC. Then, the survival analysis of TCGA-UCEC was performed. Futher, the gene set enrichment analysis (GSEA) was carried out to reveal the potential molecular signaling pathway in UCEC associated with CXCL9 expression. Moreover, the immunohistochemistry (IHC) assay of our validation cohort (n=124) from human specimens were used to demonstrate the latent significance of CXCL9 in UCEC. The bioinformatics analysis suggested that CXCL9 expression was significantly upregulated in UCEC patients; and hyper-expression of CXCL9 was related to prolonged survival. the GSEA enrichment analysis showed various immune response-related pathways, including T/NK cell, lymphocyte activation, cytokine-cytokine receptor interaction network, and chemokine signaling pathway, mediated by CXCL9. In addition, the cytotoxic molecules (IFNG, SLAMF7, JCHAIN, NKG7, GBP5, LYZ, GZMA, GZMB, and TNF3F9) and the immunosuppressive genes (including PD-L1) were positively related to the expression of CXCL9. Further, the IHC assay indicated that the CXCL9 protein expression was mainly located in intertumoral and significantly upregulated in the UCEC patients; UCEC with high intertumoral CXCL9 cell abundance harbored an improved prognosis; a higher ratio of anti-tumor immune cells (CD4+, CD8+, and CD56+ cell) and PD-L1 was found in UCEC with CXCL9 high expression. Overexpressed CXCL9 correlates with antitumor immunity and is predictive of a favorable prognosis in UCEC. It hinted that CXCL9 may serve as an independent prognostic biomarker or therapeutic target in UCEC patients, which augmented anti-tumor immune effects to furnish survival benefits.

The influence of biomarkers on carcinogenesis has been investigated extensively. Whether they promote carcinogenesis or work against cancer development remains to be elucidated. To the best of our knowledge, the novel molecule cluster of differentiation 200 (CD200) has not been studied on human breast cancer subjects. The present study aimed to evaluate interleukin-1β (IL-1β), C-X-C motif chemokine ligand 8 (CXCL8), cancer antigen 15.3 (CA 15.3) and the soluble CD200 (sCD200) levels in the serum samples of breast carcinoma patients in order to predict their role in breast carcinoma. The subjects included individuals with early and advanced stage breast cancers, as well as healthy controls. Commercially available ELISA kits were used to measure the serum concentrations of sCD200, IL-1β, CXCL8, CA 15.3, C-reactive protein (CRP) and leukocyte count. A total of 130 subjects were recruited; 50 early stage cancer, 50 advanced stage and 30 control subjects. Serum sCD200, CXCL8, IL-1β and CRP levels were significantly higher in the early as well as the advanced stage breast cancer patients compared to the control group. The level of CA 15.3 was statistically different between early and advanced stage. There were significant positive correlations between IL-1β and CXCL8, and IL-1β and serum sCD200 levels in the control group. These correlations did not persist in the early or the advanced stage cancer groups except CRP and CA 15.3, but new correlations appeared between serum sCD200 level and leukocyte count for advanced stage breast cancer group. Multivariate regression correlation analysis revealed positive correlation between IL-1β and sCD200; and IL-1β and CXCL8. In conclusion, sCD200, CXCL8, CA 15.3 and IL-1β are proinflammatory molecules and their levels are influenced in breast cancer patients.

Epigenetic alterations of CXCL5 in Cr(VI)-induced carcinogenesis.