Anti-Sry-like high mobility group box (SOX) 1 antibodies (abs) are partly characterized onconeural autoantibodies (autoabs) due to their correlation with neoplastic diseases. Anti-SOX1 abs are associated with various clinical manifestations, including Lambert-Eaton myasthenic syndrome (LEMS) and paraneoplastic cerebellar degeneration (PCD). However, the clinical characteristics of patients with anti-SOX1 abs have not been described in detail. This review systematically explores the reported patients with anti-SOX1 abs and analyzes these cases for demographic characteristics, clinical features, coexisting neuronal autoabs, neuroimaging findings, treatment, and clinical outcomes. In addition, considering that PCD is the most common paraneoplastic neurological syndrome and that the association between PCD and anti-SOX1 abs remains unclear, we focus on the presence of autoabs in relation to PCD and associated tumors. PCD-associated autoabs include various intracellular autoabs (e.g., anti-Hu, anti-Yo, anti-Ri, and anti-SOX1) and cell-surface autoabs (anti-P/Q-type voltage-gated calcium channel). Commonly involved tumors in PCD are small-cell lung cancer (SCLC), gynecological, and breast tumors. LEMS is the most common clinical symptom in patients with anti-SOX1 abs, followed by PCD, and multiple neuronal autoabs coexist in 47.1% of these patients. SCLC is still the predominant tumor in patients with anti-SOX1 abs, while non-SCLC is uncommon. No consistent imaging feature is found in patients with anti-SOX1 abs, and there is no consensus on either the therapy choice or therapeutic efficacy. In conclusion, the presence of anti-SOX1 abs alone is a potential predictor of an uncommon paraneoplastic neurological disorder, usually occurring in the setting of LEMS, PCD, and SCLC. The detection of anti-SOX1 abs contributes to an early diagnosis of underlying tumors, given the diversity of clinical symptoms and the absence of characteristic neuroimaging features.

• SOXB1 transcription factors
• antibodies
• carcinoma
• non-small-cell lung
• paraneoplastic cerebellar degeneration
• small cell lung carcinoma

• Alternative Splicing
• Animals
• Carcinoma, Non-Small-Cell Lung/genetics
• Carcinoma, Non-Small-Cell Lung/metabolism
• Cell Line, Tumor
• Computational Biology
• Gene Deletion
• Gene Silencing
• Genetic Engineering
• Genome, Human
• HeLa Cells
• Humans
• Lung Neoplasms/genetics
• Lung Neoplasms/metabolism
• Mice
• Mutation
• Neoplasm Transplantation
• Neuro-Oncological Ventral Antigen
• Phenotype
• Protein Binding
• RNA, Small Interfering/metabolism
• RNA-Binding Proteins/genetics
• RNA-Binding Proteins/metabolism
• Telomerase/genetics
• Telomerase/metabolism
• Telomere/ultrastructure

• R00 CA197672 NCI NIH HHS
• K99 CA197672 NCI NIH HHS
• R01 CA154805 NCI NIH HHS
• R01 AG001228 NIA NIH HHS
• P30 CA142543 NCI NIH HHS
• P50 CA070907 NCI NIH HHS
• C06 RR030414 NCRR NIH HHS
• T32 CA124334 NCI NIH HHS
• U.S. Department of Health & Human Services | National Institutes of Health (NIH)

Paraneoplastic syndromes are signs or symptoms that occur as a result of organ or tissue damage at locations remote from the site of the primary tumor or metastases. Paraneoplastic syndromes associated with lung cancer can impair various organ functions and include neurologic, endocrine, dermatologic, rheumatologic, hematologic, and ophthalmological syndromes, as well as glomerulopathy and coagulopathy (Trousseau’s syndrome). The histological type of lung cancer is generally dependent on the associated syndrome, the two most common of which are humoral hypercalcemia of malignancy in squamous cell carcinoma and the syndrome of inappropriate antidiuretic hormone secretion in small cell lung cancer. The symptoms often precede the diagnosis of the associated lung cancer, especially when the symptoms are neurologic or dermatologic. The proposed mechanisms of paraneoplastic processes include the aberrant release of humoral mediators, such as hormones and hormone-like peptides, cytokines, and antibodies. Treating the underlying cancer is generally the most effective therapy for paraneoplastic syndromes, and treatment soon after symptom onset appears to offer the best potential for symptom improvement. In this article, we review the diagnosis, potential mechanisms, and treatments of a wide variety of paraneoplastic syndromes associated with lung cancer.

• Paraneoplastic syndrome
• Small cell lung cancer
• Non-small cell lung cancer
• Symptom
• Diagnosis
• Treatment
• Endocrine
• Neurologic
• Hematologic
• Trousseau’s syndrome