The aim of this study was to confirm the association of systemic immune-inflammation index (SII) with relapse and metastasis of cervical squamous cell carcinoma (CSCC) in patients over 50 years and older. This retrospective study included 470 patients aged 50 years and older with CSCC who were treated at the Second Affiliated Hospital of Dalian Medical University between January 2020 and January 2023. The patients were divided into two groups according to median SII: high SII (n = 235) and low SII (n = 235). Univariate and multivariate logistic regression analysis, subgroup analysis, and receiver operating characteristic curve (ROC) analysis were used to explore the association of SII with relapse and metastasis. The total population was 470, of which 161 (34%) relapsed and 133 metastasized (28.3%). Compared with low SII, high SII group had higher probability of relapse and metastasis (P < 0.05). Multivariate logistic regression analysis showed that, after adjusting for all confounding factors, each additional standard deviation in SII increased the risk of relapse by 28.5%, and the risk of relapse was 1.568 times higher for high SII than for low SII (P < 0.05). In addition, each additional unit in log10SII and LnSII increased the risk of metastasis by 178.4% and 56%, respectively (P < 0.05). Moreover, in subgroups of patients aged 65 years or older, postmenopausal, with uterine fibroids, without HPV infection, without hypertension, without diabetes, and without undergoing radical cervical cancer, higher levels of SII remained significantly associated with an increased risk of metastasis (P < 0.05). In addition, ROC analysis indicated that SII had a certain predictive value for both relapse and metastasis (AUC = 0.599 and 0.617). Higher levels of SII are significantly associated with a higher risk of relapse and metastasis, indicating that SII may have important clinical value in the prognosis assessment of CSCC.

Our previous study confirmed systemic lupus erythematosus (SLE) associated with polymorphisms of PHLDB1 and WDFY4 genes. In this study, we investigatedthe clinical relevance of PHLDB1 and WDFY4 in SLE pathogenesis and their potential as biomarkers. A total of 634 SLE patients from Sichuan University West China Hospital and 400 age- and sex-matched healthy controls were included in this study. Serum PHLDB1 and WDFY4 of SLE patients and HCs were measured by ELISA, and the laboratory indicators were collected through the electronic medical record. LASSO, logistic regression, and random forest models for SLE diagnosis and LN prediction, including variables: age, sex, serum proteins (PHLDB1/WDFY4), genotypes, cytokines, and clinical markers. Results revealed elevated PHLDB1 in SLE patients compared to controls (1.61 vs. 1.48 ng/mL, P = 0.025), while paradoxically showing suppression in LN versus Non-LN patients (1.42 vs. 1.52 ng/mL, P = 0.031). WDFY4 specifically increased in LN (666.59 vs. 594.57 pg/mL, P < 0.001) without systemic SLE alterations. Machine learning models incorporating these biomarkers demonstrated diagnostic utility, with random forest achieving AUC 0.843 for SLE discrimination and AUC 0.990 for LN prediction. LN patients concurrently exhibited distinct immune dysregulation (reduced IL-6/IL-17 and elevated TNF-α/IL-18) and renal metabolic impairment. These findings position PHLDB1 as a systemic SLE biomarker and WDFY4 as a LN-specific blood indicator, showing promise for clinical subtyping applications. Further validation of these stratified biomarkers is warranted. Our results confirm a correlation between the serum levels of PHLDB1 and the occurrence of SLE.