Structure of bacillus subtilis phage SPO2 and its DNA: similarity of Bacillus subtilis phages SPO2, phi 1O5 and SPP1.
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Animals↗
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Transducing activity of bacteriophage SPP1.
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Bacillus subtilis↗
Clonal dental pulp cells (RDP4-1, RPC-C2A) synthesize and secrete osteopontin (SPP1, 2ar).
Dental pulp cells play an important role in maintaining dental mineralized tissue throughout life. Supplementary mineralization such as reparative dentin and pulp stone frequently occurs after primary dentin formation. Dental pulp cells are thought to be closely associated with such mineralization. We found that clonal rat dental pulp cells, RDP4-1 and RPC-C2A, produce and secrete osteopontin, but do not synthesize phosphophoryn which is a major noncollagenous protein found in dentin. The dental pulp osteopontin was highly phosphorylated and identified by thrombin susceptibility and immunoprecipitation with osteopontin/2ar antibody. Osteopontin synthesis markedly increased by 12-O-tetradecanoylphorbol-13-acetate (TPA) as observed in many osteoblastic cells. This study indicates that these cells can produce osteopontin as a major phosphoprotein and suggests that the synthesis of osteopontin could be used as a characteristic marker of dental pulp cells.
Animals↗
Length polymorphism in an intron of the porcine osteopontin (SPP1) gene is caused by the presence or absence of a SINE (PRE-1) element.
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Animals↗
Alignment of partial denaturation map of bacteriophage SPP1 DNA.
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Bacillus subtilis↗
Osteopontin reduces polyspermy during in vitro fertilization of porcine oocytes.
This study was designed to determine the role of osteopontin (SPP1) in in vitro fertilization (IVF) in swine. The initial objective was to evaluate the effect of various concentrations of SPP1 (0, 0.001, 0.01, 0.1 and 1 microg/ml) on spermatozoa and oocytes during IVF. The results demonstrate that SPP1 reduced the rate of polyspermy in a dose-dependent manner (P < 0.05). SPP1 also reduced both the number of sperm in oocytes as compared to the control and the number of spermatozoa bound to the zona pellucida (ZP) (P < 0.05). High doses of SPP1 (1 microg/ml) reduced penetration and male pronucleus formation as compared to the control (P < 0.05). Interestingly, compared to the control group, medium doses of SPP1 increased fertilization efficiency (42.6% and 44.6% vs. 31.6%; P < 0.05), representing a 41% improvement for 0.1 microg/ml SPP1). The ZP of 0.1 microg/ml SPP1-treated oocytes was more difficult to digest than control oocytes (P < 0.05). The percentage of acrosome-reacted spermatozoa bound to the ZP during IVF increased after 4 h of 1.0 microg/ml SPP1 treatment compared to 0 or 0.1 microg/ml SPP1. SPP1 did not have an effect on sperm motility, progressive motility, and sperm viability. To confirm that the reduction of polyspermy was specific to SPP1, a mixture of pregnancy-associated glycoproteins was included in the IVF protocol and shown to have no effect on polyspermy. Furthermore, Western blotting demonstrated that a 50-kDa SPP1 form was present in the oviducts on Days 0, 3, and 5 in pregnant and nonpregnant gilts, and the concentration of SPP1 on Day 0 was higher than on Days 3 and 5. The current study represents the first report to demonstrate that SPP1 plays an important role in the regulation of pig polyspermic fertilization; it decreases polyspermy and increases fertilization efficiency during IVF.
Animals↗
Secreted phosphoprotein 1 (osteopontin) is expressed by stromal macrophages in cyclic and pregnant endometrium of mice, but is induced by estrogen in luminal epithelium during conceptus attachment for implantation.
Secreted phosphoprotein 1 (SPP1, osteopontin) is the most highly upregulated extracellular matrix/adhesion molecule/cytokine in the receptive phase human uterus, and Spp1 null mice manifest decreased pregnancy rates during mid-gestation as compared with wild-type counterparts. We hypothesize that Spp1 is required for proliferation, migration, survival, adhesion, and remodeling of cells at the conceptus-maternal interface. Our objective was to define the temporal/spatial distribution and steroid regulation of Spp1 in mouse uterus during estrous cycle and early gestation. In situ hybridization localized Spp1 to luminal epithelium (LE) and immune cells. LE expression was prominent at proestrus, decreased by estrus, and was nearly undetectable at diestrus. During pregnancy, Spp1 mRNA was not detected in LE until day 4.5 (day 1 = vaginal plug). Spp1-expressing immune cells were scattered within the endometrial stroma throughout the estrous cycle and early pregnancy. Immunoreactive Spp1 was prominent at the apical LE surface by day 4.5 of pregnancy and Spp1 protein was also co-localized with subsets of CD45-positive (leukocytes) and F4/80-positive (macrophages) cells. In ovariectomized mice, estrogen, but not progesterone, induced Spp1 mRNA, whereas estrogen plus progesterone did not induce Spp1 in LE. These results establish that estrogen regulates Spp1 in mouse LE and are the first to identify macrophages that produce Spp1 within the peri-implantation endometrium of any species. We suggest that Spp1 at the apical surface of LE provides a mechanism to bridge conceptus to LE during implantation, and that Spp1-positive macrophages within the stroma may be involved in uterine remodeling for conceptus invasion.
Animals↗
Multiomics Analysis Reveals Therapeutic Targets for Chronic Kidney Disease With Sarcopenia.
BACKGROUND: The presence of sarcopenia in patients with chronic kidney disease (CKD) is associated with poor prognosis. The mechanism underlying CKD-induced muscle wasting has not yet been fully explored. This study investigates the influence of renal secretions on muscles using multiomics sequencing. METHODS: The kidney transcriptome analysis by RNA-seq and protein profiling by tandem mass tag (TMT), serum TMT and muscle TMT were performed in CKD established using 0.2% adenine and control mice. Spp1 recombinant protein was used to study its effect on myotube atrophy in vitro. In animal experiments on CKD, pharmacological inhibition of Spp1 was used to explore the role of Spp1 in skeletal muscle wasting. Transcriptome analysis was performed to identify differentially expressed genes (DEGs) in the gastrocnemius muscle following Spp1 pharmacological inhibition. RESULTS: In the renal transcriptome and TMT, 503 and 377 proteins/genes respectively were co-upregulated and co-downregulated. In the serum TMT of CKD and normal control (NC) mice, 22 upregulated and 7 downregulated differentially expressed proteins (DEPs) showed the same expression patterns as those in the kidney transcriptome and TMT analysis. Based on bioinformatics analysis and reported studies, we selected Spp1 for further validation. Spp1 recombinant protein was added to C2C12 myotubes in vitro, and the results indicated that Spp1 significantly increased the protein levels of the muscle atrophy marker (Murf-1) and promoted the smaller myotubes (all p < 0.05). Compared with NC mice, Spp1 mRNA and protein levels were significantly upregulated in the kidneys of CKD mice, and the serum concentration of Spp1 was also markedly increased (all p < 0.05). In animal experiments, pharmacological inhibition of Spp1 increased the weights of gastrocnemius and tibialis anterior muscles (p < 0.05) and improved muscle atrophy phenotype. Transcriptome analysis showed that DEGs in the gastrocnemius muscle following Spp1 pharmacological inhibition were enriched in protein digestion and absorption, glucagon signalling pathway, apelin signalling pathway and ECM-receptor interaction pathway. CONCLUSIONS: Our study is the first to establish a regulatory network of kidney-muscle crosstalk to explore the potential mechanism of CKD-related sarcopenia. Employing multiomics analysis, cellular assessment and animal experiments, we have identified that Spp1 could potentialy serve as a promising therapeutic target for CKD patients with sarcopenia.
Sarcopenia↗
Role of fission yeast primase catalytic subunit in the replication checkpoint.
To investigate the cell cycle checkpoint response to aberrant S phase-initiation, we analyzed mutations of the two DNA primase subunit genes of Schizosaccharomyces pombe, spp1(+) and spp2(+) (S. pombe primase 1 and 2). spp1(+) encodes the catalytic subunit that synthesizes the RNA primer, which is then utilized by Polalpha to synthesize the initiation DNA. Here, we reported the isolation of the fission yeast spp1(+) gene and cDNA and the characterization of Spp1 protein and its cellular localization during the cell cycle. Spp1 is essential for cell viability, and thermosensitive mutants of spp1(+) exhibit an allele-specific abnormal mitotic phenotype. Mutations of spp1(+) reduce the steady-state cellular levels of Spp1 protein and compromised the formation of Polalpha-primase complex. The spp1 mutant displaying an aberrant mitotic phenotype also fails to properly activate the Chk1 checkpoint kinase, but not the Cds1 checkpoint kinase. Mutational analysis of Polalpha has previously shown that activation of the replication checkpoint requires the initiation of DNA synthesis by Polalpha. Together, these have led us to propose that suboptimal cellular levels of polalpha-primase complex due to the allele-specific mutations of Spp1 might not allow Polalpha to synthesize initiation DNA efficiently, resulting in failure to activate a checkpoint response. Thus, a functional Spp1 is required for the Chk1-mediated, but not the Cds1-mediated, checkpoint response after an aberrant initiation of DNA synthesis.
Amino Acid Sequence↗
Generation and validation of a Myh11Dre-Spp1Cre intersectional mouse model for lineage tracing of disease-associated smooth muscle cell states.
BACKGROUND: Phenotypic modulation of vascular smooth muscle cells (VSMCs) is a hallmark of vascular remodeling and cardiovascular disease. Recent lineage-tracing and single-cell transcriptomic studies have identified secreted phosphoprotein 1 (SPP1) as a prominent marker associated with disease-associated VSMC states, particularly those linked to fibrotic remodeling and vascular calcification. However, the cellular origins and fate of SPP1-associated VSMC populations remain incompletely understood. METHODS AND RESULTS: We generated a novel Spp1-rSTOPr-Cre (Spp1Cre) knock-in mouse line in which Cre recombinase is expressed from the endogenous Spp1 locus following Dre-mediated excision of a rox-flanked transcriptional STOP cassette. Correct targeting of the knock-in allele was validated by internal, 5' junction, 3' junction, and long-range PCR analyses, as well as Sanger sequencing. To establish an intersectional lineage-tracing strategy, Spp1Cre mice were crossed with Myh11DreERT2 and Rosa26-RSR-LSL-tdTomato-LSL-eGFP reporter mice, enabling permanent labeling of VSMC-derived populations following activation of the endogenous Spp1 locus. Under physiological conditions, eGFP-positive cells were detected at low frequency within the vascular wall and were predominantly negative for the contractile markers ACTA2 and MYH11. As a proof-of-principle application, eGFP-positive cells markedly expanded within atherosclerotic lesions induced by AAV-PCSK9D377Y and high-fat diet feeding. These lineage-traced cells remained largely ACTA2- and MYH11-negative, consistent with a modulated phenotype. Notably, only a minority of eGFP-positive cells expressed SPP1 or fibronectin at the time of analysis, demonstrating the utility of permanent lineage tracing for tracking cells with a history of endogenous Spp1 activation during vascular remodeling. CONCLUSION: We report the generation and validation of a novel Myh11Dre-Spp1Cre intersectional mouse model for lineage tracing of VSMC-derived populations that have activated the endogenous Spp1 locus. This genetic resource provides a valuable platform for investigating the origin, fate, and phenotypic evolution of Spp1-associated VSMC populations during vascular remodeling and cardiovascular disease.
Animals↗
Characterization of murine sphingosine-1-phosphate phosphohydrolase.
In the present study we have characterized mammalian sphingosine-1-phosphate phosphohydrolase (SPP1), an enzyme that specifically dephosphorylates sphingosine 1-phosphate (S1P) and which differs from previously described lipid phosphate phosphohydrolases. Based on sequence homology to murine SPP1, we cloned the human homolog. Transfection of human embryonic kidney 293 and Chinese hamster ovary cells with murine or human SPP1 resulted in marked increases in SPP1 activity in membrane fractions that were used to examine its enzymological properties. Unlike other known type 2 lipid phosphate phosphohydrolases (LPPs), but similar to the yeast orthologs, mammalian SPP1s are highly specific toward long chain sphingoid base phosphates and degrade S1P, dihydro-S1P, and phyto-S1P. SPP1 exhibited apparent Michaelis-Menten kinetics with S1P as substrate with an apparent K(m) of 38.5 microm and optimum activity at pH 7.5. Similar to other LPPs, SPP1 activity was also independent of any cation requirements, including Mg(2+), and was not inhibited by EDTA but was markedly inhibited by NaF and Zn(2+). However, SPP1 has some significantly different enzymological properties than the LPPs: the aliphatic cation propanolol, which is an effective inhibitor of type 1 phosphatidate phosphohydrolase activities and is only modestly effective as an inhibitor of LPPs, is a potent inhibitor of SPP1; the activity was partially sensitive to N-ethylmaleimide but not to the thioreactive compound iodoacetamide; and importantly, low concentrations of Triton X-100 and other non-ionic detergents were strongly inhibitory. Thus, in agreement with Cluster analysis which shows that outside of the consensus motif there is very little homology between SPP1s and the other type 2 lipid phosphohydrolases, SPP1s are significantly different and divergent from the mammalian LPPs.
Amino Acid Sequence↗
Steroid regulation of cell specific secreted phosphoprotein 1 (osteopontin) expression in the pregnant porcine uterus.
Secreted phosphoprotein 1 (SPP1, commonly referred to as osteopontin and formerly known as bone sialoprotein 1, early T-lymphocyte activation 1) is an extracellular matrix/adhesion molecule that is upregulated in the pregnant uterus of all mammals examined to date. This study focused on the pig, which has true epitheliochorial placentation and exhibits induction of SPP1 mRNA in luminal epithelium (LE) just before conceptus attachment and in glandular epithelium (GE) after Day 30 of pregnancy. The objective of this study was to determine steroid regulation of SPP1 mRNA and protein in porcine uterine epithelium. To examine the effect of estrogen, cyclic gilts were treated daily (Days 11-14) with 5 mg estradiol benzoate (i.m.) and hysterectomized on Day 15. To evaluate the long-term effect of pseudopregnancy, cyclic gilts were given daily injections (Days 11-15) with steroid as above and hysterectomized on Day 90. In situ hybridization showed high expression of SPP1 mRNA only in LE contiguous with apposing conceptus tissue on Day 15 of pregnancy. In contrast, estrogen injection resulted in moderate but uniform SPP1 mRNA in all LE of Day 15 nonpregnant gilts, with expression maintained through Day 90 of pseudopregnancy. SPP1 mRNA also localized to the GE of Day 90 pseudopregnant gilts, similar to expression in late gestation. Consistent with in situ hybridization results, SPP1 protein localized to the apical surface of LE in all estrogen-treated gilts and in the GE on Day 90 of pseudopregnancy. We conclude that, in pregnant pigs, SPP1 is induced by conceptus estrogen in uterine LE and is regulated in GE in a manner coincident with CL/placental progesterone production.
Animals↗
Sequence variants of the secreted phosphoprotein 1 gene are associated with total serum immunoglobulin E levels in a Japanese population.
BACKGROUND: Secreted phosphoprotein 1 (SPP1) is a cytokine with pleiotrophic immunological activities, including activation of macrophage chemotaxis and T-helper type 1 (Th1) immune responses. SPP1 gene polymorphisms have been shown to be associated with several immune inflammatory diseases including multiple sclerosis (MS), which is characterized by fewer allergic symptoms and lower numbers of allergen sensitizations. OBJECTIVE: The present study examined whether SPP1 gene polymorphisms are associated with total serum IgE levels, atopy and asthma in a Japanese population. METHODS: This case-control association analysis examined 611 subjects, including 268 subjects with asthma. We genotyped three promoter and two exon polymorphisms at SPP1: -1687A/G; -381T/C; -94 deletion/G; 5891C/T; and 7052T/C. Results Association analyses of SPP1 polymorphisms showed that homozygosities for the 5891T allele (P=0.009) and 7052C allele (P=0.001) were significantly associated with increased levels of total IgE in non-asthmatic subjects. However, these variants were not associated with asthma and atopy. Interestingly, individuals carrying the 5891C allele, which is more prevalent in patients with MS in Japanese populations, displayed significantly lower levels of total serum IgE. Individuals homozygous for the 7052C allele, which is associated with development of systemic lupus erythematosus, displayed significantly higher total serum IgE levels. CONCLUSION: These findings suggest that genetic polymorphisms in SPP1 may play a role in controlling basal levels of total serum IgE, independent of atopy.
Adult↗
Gene expression of bacteriophage SPPI. I. Phage directed protein synthesis.
A total of 23 phage specific proteins (including four head and six tail proteins) could be identified after SDS polyacrylamide gel electrophoresis of extracts from phage SPP1 infected Bacillus subtilis cells. The total molecular weight of the proteins amounts to approximately 1.9 X 10(6) daltons, equivalent to the majority of the coding capacity of SPP1 DNA. It can thus be assumed that almost all SPP1 coded proteins have been identified. Protein assignments to phage cistrons were made by analysis of extracts from nonpermissive cells infected with sus-mutants. The SPP1 specified proteins can be subdivided into three groups on the basis of the time of their synthesis during the latent period. Host protein synthesis is not significantly affected by SPP1 infection. Normal expression of host genes appears to be essential for SPP1 growth.
Bacillus subtilis↗
Construction and use of SPP1v, a viral cloning vector for Bacillus subtilis.
A unique BamHI restriction site has been inserted into a nonessential region of the genome of a deletion mutant of phage SPP1. Construction of this phage, designated SPP1 v, required the in vitro conversion of a BclI site to a BamHI site. SPP1 v has been used as a vector phage to clone BamHI, BglII and BclI-generated restriction fragments of DNA. A direct selection for recombinants has been developed. Transfection with SPP1 v requires intact, genomic-length molecules, and cleavage with BamHI destroys the transfecting ability of this DNA. Recombinants in which the BamHI site has been destroyed by ligation to Bg/II or BclI-generated fragments of DNA become resistant to BamHI digestion after ligation and are active in transfection. Cloning of DNA containing BamHI sites has been accomplished by using the enzyme Bst1503I to methylate BamHI sites before insertion, and so to protect them during the BamHI digestion used to select against vector molecules. The in vitro construction of SPP1 v generated XmaIII sites directly adjacent to, and on both sides of the inserted BamHI site. This permits precise excision of cloned DNA even when cloning destroys the BamHI insertion site. Restriction-enzyme generated fragments of DNA in the size range of 0 to 4 Md have been cloned, including a full-length copy of plasmid pUB110, almost the complete sequence of plasmid pBR322, and a sequence of DNA that carried the lambda cos site.
Bacillus subtilis↗
Evaluation in beef cattle of six deoxyribonucleic acid markers developed for dairy traits reveals an osteopontin polymorphism associated with postweaning growth.
The objectives of this study were to 1) estimate the allelic frequencies in US beef cattle of 6 DNA markers reported to be associated with variation in dairy production traits; and 2) evaluate the association of these markers with beef production traits. Several genetic markers have been associated with milk yield or composition, including polymorphisms in secreted phosphoprotein 1 (SPP1; also called osteopontin), growth hormone receptor (GHR), casein S1 (CSN1S1), diacylglycerol O-acyltransferase 1 (DGAT1), peroxisome proliferator-activated receptor gamma co-activator-1alpha (PPARGC1A), and ATP-binding cassette subfamily G (white) member 2 (ABCG2). Allelic frequencies for these 6 markers, and their association with 21 phenotypes, were evaluated in 2 crossbred beef cattle populations that sample influential industry sires. Five of 6 markers were segregating in beef cattle populations; the exception was ABCG2. The SPP1 marker was associated with yearling weight (P = 0.025), live weight at slaughter (P = 0.016), postweaning ADG (P = 0.007), and HCW (P = 0.007) in a large, multisire population representing the 7 most populous beef breeds in the United States. Postweaning growth trait associations were confirmed in an independent population of similar construction, including sires from tropically adapted breeds. The SPP1 marker was associated with yearling weight (P = 0.034), live weight at slaughter (P = 0.011), and postweaning ADG (P = 0.015) and showed a trend toward association with HCW (P = 0.083) in this population. Whereas DGAT1, GHR, and CSN1S1 polymorphisms showed association with some traits in individual populations, the lack of consistent predictive merit between populations indicates they may not be suited for beef cattle selection. No significant associations were observed for the PPARGC1A marker and any of 21 recorded traits, indicating this marker had no apparent value in selection for the beef cattle traits tested in these populations. The SPP1 marker had consistent associations and effect sizes (10.5 to 11.5 kg of live weight at slaughter) in both populations, providing strong evidence for utility of the SPP1 marker for postweaning growth in beef cattle.
Animals↗
Discovery and validation of a prognostic SPP1/PLAU signature in HPV-negative oropharyngeal squamous cell carcinoma.
BACKGROUND: This study aimed to identify and validate robust prognostic biomarkers for oropharyngeal squamous cell carcinoma (OPSCC), with a specific focus on the high-risk HPV-negative subtype. METHODS: Integrated bioinformatics analysis was performed on transcriptomic data from four GEO datasets (n = 418 samples). Differentially expressed genes (DEGs) were identified, and a protein-protein interaction (PPI) network was constructed for the most dysregulated genes. Key modules were analyzed via survival analysis and multivariate Cox regression. The top candidate genes were validated at the protein level using immunohistochemistry (IHC) in an independent cohort of 304 OPSCC patients. RESULTS: A 33-gene module related to extracellular matrix organization showed significant prognostic association. It stratified patients into high- and low-risk groups with markedly different overall survival (HR = 2.71, p < 0.001). From this module, SPP1 and PLAU were identified as independent prognostic factors through multi-step screening. Both genes were significantly overexpressed in tumors (approximately 20-fold and 10-fold, respectively, p < 0.001), with high expression strongly correlated with advanced tumor stage (p < 0.01) and, notably, the HPV-negative subtype (p < 0.001). In survival analysis, high expression of either SPP1 or PLAU was associated with poorer overall survival (SPP1: p < 0.001; PLAU: p < 0.001) and progression-free survival (p < 0.001). IHC validation confirmed high protein expression in 69.7% (SPP1) and 54.8% (PLAU) of cancer tissues. A prognostic nomogram integrating the SPP1/PLAU signature with clinical variables was constructed with strong predictive accuracy (C-index = 0.75). CONCLUSION: The SPP1/PLAU dual-gene signature is a robust and independent prognostic biomarker for OPSCC, with particular clinical utility for stratifying high-risk HPV-negative patients.
Humans↗
CS Ratio is an immune-related prognostic biomarker for cervical cancer.
BACKGROUND: The tumor microenvironment (TME) plays a crucial role in cancer progression but its complex structure significant variability among patients present considerable challenges for research. Recent studies have demonstrated that macrophage polarization states defined by the expression levels of CXCL9 SPP1 (CS Ratio) are more prognostically relevant than traditional M1/M2 markers. The CS polarization state reflects a highly coordinated network of pro-tumor anti-tumor variables offering a simplified yet effective immune response indicator for the complex TME. The CS Ratio has been shown to correlate with the abundance of anti-tumor immune cells the gene expression programs of tumor-infiltrating cells responses to immunotherapy. Cervical cancer, one of the most common gynecological malignancies, still faces limited therapeutic options. CXCL9, a member of the CXC chemokine family, plays a critical role in immune regulation, inflammation, tumor growth, angiogenesis, and metastasis. Similarly, SPP1, a cytokine, influences immune-related pathways by regulating molecules such as interferon-γ and interleukin-12. However, no studies have systematically investigated the role of the CS Ratio in cervical cancer or its relationship with immunotherapy characteristics. Research in this area could provide critical insights into the role and clinical potential of the CS Ratio in cervical cancer and related tumors. METHODS: The expression ratio of CXCL9 to SPP1 was analyzed in cervical cancer patients using data from the Gene Expression Omnibus (GEO) database, which revealed significant differences. Data for cervical cancer patients were obtained from The Cancer Genome Atlas (TCGA) database. The optimal cutoff value for the CS Ratio was determined using the maxstat package in R, and Kaplan-Meier (KM) survival curves were constructed. Patients were categorized into High and Low groups based on the median CS Ratio. Immune scores were analyzed, and immune cell infiltration was assessed using CIBERSORT. Differences in the CS Ratio were evaluated across patients with varying pathological T stages and FIGO stages. Additionally, receiver operating characteristic (ROC) analysis was performed using the pROC package in R to calculate the area under the curve (AUC). Univariate and multivariate Cox regression analyses were performed to evaluate the potential of the CS Ratio as an independent prognostic factor in cervical cancer. A Cox regression-based nomogram integrating four key features was subsequently developed for the TCGA-CESC cohort. Nomogram performance was assessed using calibration curves and ROC analysis. RESULTS: The CS Ratio was significantly lower in cervical cancer patients compared to normal controls (P < 0.05). KM survival curves indicated that patients in the CS High group exhibited better prognoses. Immune score analysis revealed significantly higher immune scores (P < 0.05) and lower tumor purity (P < 0.05)in the CS High group compared to the Low group. CIBERSORT analysis revealed significantly higher proportions of CD8+ T cells (P < 0.05) and M1 macrophages (P < 0.05), and a significantly lower proportion of M2 macrophages (P < 0.05), in the CS High group compared to the Low group. The CS Ratio significantly decreased with advancing FIGO stage (P < 0.05). Both univariate (P < 0.05) and multivariate Cox regression analyses (P < 0.05) confirmed the CS Ratio as an independent prognostic factor. ROC analysis demonstrated that the CS Ratio had higher AUC values for predicting 1-year (AUC=0.69), 3-year (AUC=0.66), and 5-year OS (AUC=0.68) than CXCL9 or SPP1 alone. The Cox regression-based nomogram integrating four key features demonstrated predictive capability for 1-, 3-, and 5-year OS in CESC patients (Concordance Index = 0.751; 95% CI: 0.678-0.824; p = 1.50Í10-11). Significant survival differences were observed between the high-risk and low-risk groups based on the nomogram score. ROC analysis yielded high AUC values for survival prediction: 0.85 (95% CI: 0.94-0.75) at 1-year, 0.74 (95% CI:0.84-0.64) at 3-year, and 0.72 (95% CI:0.84-0.61) at 5-year. CONCLUSION: The CS Ratio may serve as a more effective prognostic biomarker for cervical cancer patients.
CXCL9↗