Table 1.

Functions of paraneoplastic antigens that caused the generation of onconeural autoantibodies in paraneoplastic syndrome-associated ovarian cancer.

Paraneoplastic syndrome in association with ovarian cancer	Onconeural antibodies targeting paraneoplastic antigens in PNS-associated ovarian cancer	Function of paraneoplastic antigens that elicit immune responses to generate onconeural antibodies	NCBI reference sequence accession number	References
Paraneoplastic cerebellar degeneration	Yo antibody or Purkinje cell cytoplasmic antibody type 1 (PCA-1) targets CDR2 antigen	CDR2 interacts with c-myc and downregulates c-myc dependent transcription in tumor cells. CDR2 is involved in mitotic cell division.	NM_001802	O'Donovan et al. (2010); Takanaga et al. (1998)
Paraneoplastic cerebellar degeneration	Zic-4 antibodies	Zic proteins are transcription factors that have zinc finger domains that bind DNA of the target genes to regulate their transcription activity. The expression of these genes occurs during the development of cerebellum.	BC136339	Houtmeyers et al. (2013); Kerasnoudis et al. (2011)
Paraneoplastic cerebellar degeneration	Carbonic anhydrase-related protein VIII (CARP VIII) antibodies	CARP VIII protein is related to carbonic hydrase family but does not have catalytic activity of hydration of CO2. It is expressed in brain Purkinje cells and also in different cancers like lung and has been reported to cause proliferation and invasion of tumor cells thus resulting in tumor growth and progression.	NM_004056	Akisawa et al. (2003); Aspatwar et al. (2010)
Paraneoplastic cerebellar degeneration	Creatine kinase B (CKB) antibodies	Creatine kinase isoenzyme is highly expressed in brain. CKB is involved in reversible catalytic transfer of phosphate between creatine kinase and ATP, thus maintaining energy homeostatis in the cells.	NM_001823	Tetsuka et al. (2013)
Paraneoplastic encephalomyeloneuropathy	P/Q and N type calcium-channel antibodies	Neurotransmission is triggered by Calcium influx through P/Q and N type calcium-channel at the central and peripheral synapses.	X99897 M94172	Currie and Fox (1997); Lennon et al. (1995)
Encephalomyelitis	Amphiphysin antibodies	Amphiphysin is mostly present in the brain tissue and exist in two isomeric forms Amphiphysin 1 and 2. It binds to Dynamin 1 through its C-terminal SH3 domain that leads to synaptic vesicle endocytosis at the nerve terminals. It also has N terminal (BIN/amphiphysin/Rvs) BAR domain that helps it to sense membrane curvature and this property is important for coordinating vesicle formation and fission.	NM_001635	Yoshida et al. (2004)
Myositis	Jo-1 autoantibodies that target the Histidyl-tRNA synthetase antigen (HARS) or Jo-1 antigen	HARS catalyzes the transfer of Histidine amino acid to its cognate tRNA during protein synthesis. Hars is responsible for causing autoimmunity in antisynthetase syndrome by producing Jo-1 antibodies that undergo class switching and affinity maturation that are driven by T-cell activation which ultimately causes inflammation and tissue damage.	AAX99363.1	Raben et al. (1994); Zahr and Baer (2011)
Myositis	SRP-54 autoantibodies	Signal recognition particle 54 kDa protein, one of six subunits in the signal recognition particle ribonucleoprotein complex.	U51920.1	Hainzl et al. (2002); Suzuki et al. (2015)
Myositis, Myasthenia gravis	Cortactin antibodies	Cortactin aids in actin assembly by binding actin. It is a signaling protein involved in tumor invasion as well as cell adhesion, migration and endocytosis.	BC008799.2	Berrih-Aknin (2014)
Dermatomyositis	Tif-1 gamma (Trim33) autoantibodies or anti-p155/140	Tif1-gamma (Trim33) is a E3 ubiquitin ligase. Its function as a tumor suppressor depends on Trim33 dependent degradation of β-catenin.	NG_023287.1	Masiak et al. (2016); Xue et al. (2015)
Dermatomyositis	NXP-2 autoantibodies, or anti-MJ antibodies	NXP-2 protein is a nuclear matrix-associated protein. It plays an important role in RNA processing due to its RNA binding activity. It is involved in RNA metabolism.	NM_015358.2	Ishikawa et al. (2012); Kimura et al. (2002)
Dermatomyositis	CDR2L antibodies	The function of CDR2L is currently unknown. It is a paralog of CDR2 with 50% sequence homology.	NM_014603	Eichler et al. (2013)
Idiopathic inflammatory myopathy, Sjo¨gren's syndrome and Systemic lupus erythematosus (SLE)	Ro52 autoantibodies	Ro52 protein contains 3 motifs, namely, RING-finger motif, a B-box, and a coiled-coil domain and so it belongs to tripartite motif (TRIM) family. Ro52 protein has E3-ligase activity and it's overexpression in B cells reduces cell proliferation and causes an increase in apoptotic cell death.	NM_003141.3	Espinosa et al. (2006); Rutjes et al. (1997)
Antiphospholipid antibody syndrome	Phospholipid antibodies	Phospholipids can form lipid bilayers that are major components of cells. Different enzymes act on phospholipids to form secondary products that act as a second messenger in signal transduction pathways. In prostaglandin signaling pathways, phospholipids act as a prostaglandin precursor substrate for lipase enzyme.	N/A	Lands and Samuelsson (1968); Ruffatti et al. (1994)
No association of ovarian cancer with paraneoplastic syndrome	Ri antibodies bind to Nova-1 (neuro-oncological ventral antigen-1)	Nova-1, also called paraneoplastic opsoclonus-myoclonus ataxia (POMA) antigen. is a sequence specific RNA binding protein that is involved in the splicing of neuronal pre-mRNA.	NM_002515	Drlicek et al. (1997); Jensen et al. (2000)

Table 1 provides a brief description of various paraneoplastic antigens that are capable of eliciting immune responses in ovarian cancer that may be associated with different paraneoplastic syndromes. Different functions of these paraneoplastic antigens along with their NCBI reference sequence accession numbers are also listed in Table 1.