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Failed neuroprotection leads to the initiation of several diseases. SOX1 plays many roles in embryogenesis, oncogenesis, and male sex determination, and can promote glioma stem cell proliferation, invasion, and migration due to its high expression in glioblastoma cells. The functional versatility of the SOX1 gene in malignancy, epilepsy, and Parkinson’s disease, as well as its adverse effects on dopaminergic neurons, makes it an interesting research focus. Hence, we collate the most important discoveries relating to the neuroprotective effects of SOX1 in brain cancer and propose hypothesis worthy of SOX1’s role in the survival of senescent neuronal cells, its roles in fibroblast cell proliferation, and cell fat for neuroprotection, and the discharge of electrical impulses for homeostasis. Increase in electrical impulses transmitted by senescent cells affects the synthesis of neurotransmitters, which will modify the brain cell metabolism and microenvironment.

Objective This meta-analysis evaluates the diagnostic value of SOX1 methylation across different cervical cancer types, including squamous cell carcinoma and adenocarcinoma, to assess its efficacy as a biomarker. Methods We reviewed studies published up to March 2024, employing a PICOS-based search strategy in databases like PubMed and Web of Science. We included clinical studies providing diagnostic performance indicators while excluding non-clinical and small-sample studies. Meta-Disc1.4 and Stata15.1 were used for statistical analyses focusing on SOX1 methylation’s sensitivity, specificity, and diagnostic odds ratio. Results Twelve articles encompassing 18 studies with 3,213 subjects were analyzed. The overall DOR for SOX1 methylation in cervical cancer diagnosis was 68.95 (95%CI: 27.63-172.07), with a Summary Receiver Operating Characteristic AUC of 0.92, indicating high diagnostic accuracy. Specifically, the DOR for adenocarcinoma was 87.57 (95%CI: 7.05-1087.44) with an AUC of 0.89, and for squamous cell carcinoma, it was 245.87 (95% CI: 26.49-2282.40) with an AUC of 0.93, reflecting significant diagnostic potential for both cancer types. No substantial publication bias was detected ( P  > 0.10). Conclusion SOX1 gene methylation demonstrates significant diagnostic value for both adenocarcinoma and squamous cell carcinoma of the cervix, particularly effective in large sample sizes and cervical exfoliated cell samples for early detection and screening, supporting its utility as a reliable biomarker.

ABSTRACT SOX1 is a member of the SOXB1 subgroup of transcription factors involved in early embryogenesis, CNS development and maintenance of neural stem cells. The structure and regulation of the human SOX1 locus has been less studied than that of SOX2 , another member of the SOXB1 subgroup for which an overlapping transcript has been reported. Here we report that the SOX1 locus harbours a SOX1 overlapping transcript ( SOX1 - OT ), and describe expression, splicing variants and detection of SOX1 - OT in different stem and cancer cells. RT-PCR and RACE experiments were performed to detect and characterise the structure of SOX1 - OT in neuroprogenitor cultures and across different cancer cell lines. SOX1 - OT was found to present a complex structure including several unannotated exons, different transcript variants and at least two potential transcription start sites. SOX1 - OT was found to be highly expressed in differentiated neural stem cells across different time points of differentiation, and its expression correlated with SOX1 gene expression. Concomitant expression of SOX1 and SOX1 - OT was further observed in several cancer cell models. While the function of this transcript is unknown, the regulatory role reported for other lncRNAs strongly suggests a possible role for SOX1 - OT in regulating SOX1 expression, as previously observed for SOX2 . The elucidation of the genetic and regulatory context governing SOX1 expression will contribute to clarifying its role in stem cell differentiation and tumorigenesis.

Objective To describe the clinical associations of SOX1 antibodies (SOX1-Abs), determine the accuracy of various detection techniques, and propose laboratory criteria to identify definite paraneoplastic neurological syndromes (PNS) associated with SOX1-Abs. Methods Single-center, retrospective study of patients referred to the French Reference Center between 2009 and 2019 for confirmation of SOX1-Ab positivity, without concurrent neural antibodies. Patients were classified according to the updated diagnostic PNS criteria; biological samples were systematically retested with three distinct techniques (line blot, cell-based assay, indirect immunofluorescence). Results Among 77 patients with isolated SOX1-Ab positivity, 23 (29.9%) fulfilled the criteria for definite PNS; all of them had lung cancer (mostly small-cell) and presented mainly with Lambert-Eaton myasthenic syndrome (10/23) and rapidly progressive cerebellar ataxia (6/23). SOX1-Ab positivity varied depending on the laboratory methods which were used, and a single technique was not sufficient to draw conclusions about the PNS diagnosis. The combination of an antigen-specific test (line blot and/or cell-based assay) and immunofluorescence showed the highest accuracy (81.5%, 95% CI 70.0–90.1) in identifying definite PNS. Moreover, when the PNS-Care score was recalculated assigning three points at the laboratory-level only to patients with positive “antigenic-specific test + immunofluorescence” and 0 points to the remaining cases, a higher certainty for definite and non-PNS was achieved (from 41/77, 53.2%, to 60/77, 77.9%; p  < 0.001). Conclusion SOX1-Abs should be considered high-risk antibodies only when detected with a positive antigenic-specific test and immunofluorescence. Other laboratory results and clinical associations different from Lambert-Eaton myasthenic syndrome and rapidly progressive cerebellar ataxia should be carefully reassessed to rule out false positivity and alternative diagnoses.

Paraneoplastic autoimmune encephalitis (PAE) is most commonly associated with small cell lung cancer (SCLC). Anti- -aminobutyric acid B receptor (GABABR) antibodies underlie a treatable limbic syndrome, whereas anti-SRY-box transcription factor 1 (SOX1) antibodies serve as high-specificity onconeural biomarkers of SCLC-driven autoimmunity. The sequential emergence of these two antibodies during the longitudinal course of a single patient has rarely been documented. A 75-year-old man presented with episodic impaired consciousness, behavioural disturbance and rapid cognitive decline. Brain MRI showed bilateral hippocampal signal abnormalities. A cell-based assay (CBA) detected anti-GABABR antibodies at high titre in serum (1:3200) and cerebrospinal fluid (CSF; 1:1000), while a tissue-based assay (TBA) on rat brain confirmed a neuronal cell-surface staining pattern; the full paraneoplastic panel, including anti-SOX1, was negative, and initial tumour screening was unrevealing. A diagnosis of anti-GABABR encephalitis (initially regarded as non-paraneoplastic) was made and the patient improved with intravenous immunoglobulin (IVIG), high-dose corticosteroids and maintenance mycophenolate mofetil. During a refractory second relapse 5 months later, repeat CBA showed rising anti-GABA R titres (serum 1:10,000; CSF 1:1000) and newly positive anti-SOX1 antibodies (serum 1:100; CSF 1:1); a previously occult right superior mediastinal mass radiologically compatible with SCLC was identified on repeat chest CT. The diagnosis was revised to anti-GABA R/anti-SOX1 dual-antibody PAE (probable PNS by 2021 PNS-Care criteria). The family declined biopsy, PET/CT and antitumour therapy because of advanced age and frailty; repeated IVIG with continued immunosuppression achieved partial clinical stabilisation with persistent cognitive impairment. Apparently isolated anti-GABA R encephalitis can evolve into dual anti-GABABR/anti-SOX1 paraneoplastic disease, with the second antibody heralding an occult SCLC. Repeating both CBA-based and intracellular antibody panels at every clinical relapse, together with repeat thoracic imaging, is essential to avoid missing an evolving paraneoplastic aetiology.

Bisphenol A (BPA) has long been used in plastics, resins, and food packaging materials; however, extensive research has demonstrated its reproductive, developmental, and endocrine-disrupting effects. Consequently, BPA has been increasingly restricted and replaced with structural analogues. Among these, tetramethyl bisphenol F (TMBPF) has emerged as one of the most widely used substitutes, particularly in epoxy resins and food-can coatings. Although initially regarded as a safer alternative, accumulating evidence suggests that TMBPF may exert multiple toxicological effects, raising concerns about its potential developmental neurotoxicity. The present study aimed to investigate the neurodevelopmental effects of TMBPF using both in vitro and in vivo approaches. First, a developmental neurotoxicity assay employing Sox1−GFP mouse embryonic stem cells was used to evaluate cytotoxicity using the cell counting kit-8 assay and neural differentiation based on green fluorescent protein (GFP) fluorescence intensity. The results indicated developmental neurotoxic potential according to the established discrimination index. Subsequently, pregnant and lactating mice were exposed to TMBPF daily from gestational day 10.5 to postnatal day 20, and their offspring were assessed for behavioral performance as well as changes in the expression of neurodevelopment-related genes in the brain. Behavioral analyses encompassed multiple domains, including memory and learning, social behavior, anxiety-related responses, and spontaneous locomotor activity, suggesting alterations in these functional outcomes. Molecular analyses further demonstrated changes associated with dopaminergic and cholinergic signaling, synaptic plasticity, neuronal activity markers, neuropeptides, and inflammatory pathways. Collectively, these findings provide the first evidence in a mammalian model that maternal exposure to TMBPF may influence offspring neurodevelopment. These findings suggest potential implications for human exposure to TMBPF, particularly through food-contact materials, and warrant further mechanistic and dose–response studies.

SOX1 autoantibodies are considered markers of small cell lung cancer (SCLC) and paraneoplastic neurological syndromes (PNS) and are usually determined by commercial line blot in many clinical services. Recent studies suggested that SOX1 autoantibodies also occur in patients with neuropathies unrelated to SCLC, questioning the value of SOX1 autoantibodies as paraneoplastic biomarkers. Here, we compared the specificity and sensitivity of a commercial line blot (Euroimmun, Lübeck, Germany) with those of an in house cell-based assay (CBA) with HEK293 cells transfected with SOX1. Overall, 210 patients were included in the study, 139 patients with polyneuropathies without SCLC, and 71 with disorders associated with SOX1 autoantibodies detected with the in-house CBA. Forty one of these 71 cases had been referred to our laboratory for onconeuronal antibody assessment and 30/71 were patients with known PNS and SCLC. None of the patients with polyneuropathies had SOX1 autoantibodies by either line blot or CBA (specificity of the immunoblot: 100%; 95%C.I.: 97.8-100). Among the 71 patients with CBA SOX1 autoantibodies, only 53 were positive by line blot (sensitivity: 74.6%; 95%C.I.: 62.9-84.2). Lung cancer was detected in 37/41 (90%; 34 with SCLC) patients referred for onconeuronal antibody assessment and 34 of them also had a PNS. Our study confirms the association of SOX1 autoantibodies with SCLC and PNS. The line blot test misses 25% of the cases; therefore, to minimize the frequency of false negative results we recommend the use of a confirmatory test, such as CBA, in patients suspected to have a SCLC-related PNS.

The aim of this study was to assess the impact of SARS-CoV-2 infection during pregnancy on the molecular profile of human milk and to identify associations between the expression of regulatory genes and clinical parameters of newborns. The study included a group of 19 women who had COVID-19 during pregnancy and a healthy control group of 21 women. Expression levels of miR-21, miR-155, and the transcription factor SOX1 were determined in human milk using qPCR. The correlation of SOX1 expression with parameters in cord blood and infant blood was also analyzed. It was shown that maternal SARS-CoV-2 infection (during pregnancy) is associated with significantly higher levels of miR-21, miR-155, and SOX1 expression in human milk. Furthermore, strong statistical correlations were found in the study group: SOX1 expression was positively correlated with C-reactive protein (CRP) levels and lactate concentration (LAC) in arterial umbilical cord blood, while negatively correlated with glucose levels. Our research shows that SARS-CoV-2 infection during pregnancy induces changes in the molecular composition of early breast milk, promoting immunomodulatory (miR-155) and regenerative (miR-21, SOX1 ) molecules. Post-COVID-19 breast milk serves as an active biochemical communication system, providing the newborn with signals that may modulate adaptive and immune responses to the unfavorable intrauterine environment.

Objective To evaluate the clinical performance of triage strategies for HPV-positive women in rural Yunnan, China, with the aim of optimizing HPV test-based cervical cancer screening. Methods We recruited 417 HPV-positive women, who additionally underwent mRNA testing, AI-assisted cytology, PAX1 and SOX1 DNA methylation testing. We compared the sensitivity, specificity, area under the curve (AUC), and number needed to colposcopy for one cervical lesion detection of several triage approaches, for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Results Among single triage strategies, cytology demonstrated a sensitivity of 54.2% (95% CI: 33.2%–73.8%), a specificity of 75.1% (95% CI: 70.4%–79.2%), an AUC of 0.65 (95% CI: 0.53–0.77), and an number needed to colposcopy for one lesion detection of 8.5. Compared with cytology, PAX1 methylation exhibited superior sensitivity (87.5%, 95% CI: 66.5%-96.7%) and specificity (90.6%, 95% CI: 87.1%-93.2%), with an improved AUC of 0.89, and a reduced colposcopy referral of 2.8. Adding SOX1 to PAX1 maintained sensitivity (87.5%) but slightly reduced specificity (88.3%), resulting in an AUC of 0.88. mRNA testing showed higher sensitivity (75.0%) but lower specificity (44.5%) and a declined AUC (0.60). Among combined triage strategies, HPV-16/18 genotyping with reflex cytology for non-16/18 types yielded a sensitivity of 62.5%, a specificity of 54.5%, and an AUC of 0.59. HPV-16/18 genotyping with reflex PAX1/SOX1 methylation improved sensitivity to 91.7% and specificity to 64.1%, with an AUC of 0.78. Conclusion PAX1 methylation triage demonstrated better clinical performance and required fewer colposcopy referrals than cytology triage. It showed good potential as an triage strategy for HPV-positive women in rural Yunnan. The addition of SOX1 methylation or integration with HPV genotyping did not significantly enhance its clinical performance.

The aim of this study is to assess the diagnostic and screening performance of a standardized methylation-specific real-time PCR assay targeting and genes for cervical cancer in a Chinese cohort. Genomic DNA was extracted from cervical exfoliated cells and converted by sodium bisulfite and then analyzed by qMSP assay. Ct values were collected for and as target genes and as an endogenous reference gene. The samples included 295 cervicitis, 111 LSIL (low-grade squamous intraepithelial lesion), 51 HSIL (high-grade squamous intraepithelial lesion) and 30 cervical cancer. The Ct values decreased with the progression of cervical cancer from cervicitis, through LSIL and HSIL to cancer. The difference in Ct values between cytological grades was highly significant (p≤0.01) between grades either for or for except the difference between cervicitis and LSIL of . With the Ct cut-off values of gene and gene 38.6 and 38 and with the / in combination, the positive rate of methylation in invasive cancer tissues was 100%, in contrast to 11.5% (95% CI: 8.67%-14.33%) in cervicitis tissues, 45.1% (95% CI: 40.68%-49.52%) in LSIL tissues, and 68.5% (95% CI: 64.37%-72.63%) in HSIL tissues. The specificity and sensitivity of differentiating tumors from cervicitis were 0.957 (95% CI: 0.939-0.975) and 1.00, respectively. The specificity and sensitivity of differentiation between cervicitis+LSIL and HSIL+cervical cancer were 0.881 (95% CI: 0.852-0.91) and 0.748 (95% CI: 0.709-0.787), respectively. / methylation could be translated into clinical practice for cervical neoplasia detection.