The Expression and Clinical Significance of C1orf106 in Low-Grade Serous Ovarian Cancer

Abstract

Aim: Low-grade serous ovarian cancer (LGSOC) is a rare subtype of ovarian cancer with distinct biological behavior. This study aimed to identify new biomarkers with potential diagnostic and prognostic value for LGSOC.

Methods: Gene-expression data were downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified using R. Functional enrichment analyses were conducted to determine the biological functions and signaling pathways associated with DEGs. The mitogen-activated protein kinase (MAPK) pathway-related gene, chromosome 1 open reading frame 106 (C1orf106), was selected as the target gene. Immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to verify its expression. Associations between C1orf106 expression and the clinical features of patients were analyzed using the chi-square (χ²) test. Prognostic significance was evaluated with survival analyses.

Results: A total of 3099 upregulated and 4968 downregulated genes were identified in LGSOC. Gene set enrichment analysis (GSEA) demonstrated significant alterations in KRAS signaling and metabolic pathways between LGSOC and healthy controls. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses revealed enrichment in immune response and MAPK pathway alterations. Immunohistochemistry and qRT-PCR confirmed that C1orf106 expression in LGSOC tissues was significantly higher than in normal ovarian tissues. Clinically, high C1orf106 expression was associated with lower BMI (< 25 kg/m²), the absence of visible residual disease, and improved progression-free survival (PFS) and overall survival (OS) in univariate Cox and Kaplan-Meier analyses.

Conclusions: C1orf106 may serve as a promising marker for the diagnosis and prognosis of LGSOC.

Keywords: C1orf106; INAVA; bioinformatics; low‐grade serous ovarian cancer; survival analysis.

FIGURE 1

Differentially Expressed Genes (DEGs) and Functional Enrichment Analysis in Low‐Grade Serous Ovarian Cancer (LGSOC). (a) Volcano plot of DEGs between LGSOC (n = 10) and normal human ovarian surface epithelia (NOSE; n = 3). (b) Heatmap of the top 30 DEGs (N = NOSE samples; L = LGSOC samples). (c) Gene set enrichment analysis (GSEA) demonstrated upregulation of KRAS‐associated hallmarks and downregulation of oxidative phosphorylation pathways. Normalized enrichment scores (NES), p‐values, and false discovery rates (FDR) are shown for each pathway. (d) Gene Ontology (GO) analysis revealed significant enrichment of immune‐related terms, including positive regulation of T cell activation, antigen processing and presentation, and major histocompatibility complex (MHC) class II receptor activity. (e) Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis identified enrichment of Wnt signaling, T helper 17 (Th17), T helper 1 (Th1), T helper 2 (Th2) cell differentiation, phagosome, cell adhesion molecules, allograft rejection and complement/coagulation cascades.

FIGURE 2

Protein–Protein Interaction (PPI) Network of Differentially Expressed Genes (DEGs). The PPI network was constructed to illustrate associations among DEGs between low‐grade serous ovarian cancer (LGSOC) and normal human ovarian surface epithelia (NOSE). Nodes represent proteins encoded by DEGs, and edges represent predicted protein–protein interactions.

FIGURE 3

Identification of Chromosome 1 Open Reading Frame 106 (C1orf106) as a Candidate Target Gene. (a) Gene Ontology (GO) analysis revealed significant enrichment of mitogen‐activated protein kinase (MAPK) pathway–related terms. (b) Venn diagram showing the overlap between the top 30 differentially expressed genes (DEGs) and those enriched in MAPK‐related pathways. (c) Heatmap showing DEGs involved in GO:0043410 (positive regulation of the MAPK cascade).

FIGURE 4

Clinical Significance of Chromosome 1 Open Reading Frame 106 (C1orf106) Expression in Low‐Grade Serous Ovarian Cancer (LGSOC). (a) Representative immunohistochemical (IHC) staining (×400 magnification) and quantitative reverse transcription polymerase chain reaction (qRT‐PCR) results comparing LGSOC and normal ovarian tissues. (b) Violin plots showing immunoreactive scores (IRS) of LGSOC (n = 52) and normal ovarian tissues (n = 50). (c) Relative C1orf106 messenger RNA (mRNA) expression levels in LGSOC versus normal tissues, as determined by qRT‐PCR (p < 0.05). (d) Kaplan–Meier survival curves for progression‐free survival (PFS) stratified by C1orf106 expression. (e) Kaplan–Meier survival curves for overall survival (OS) stratified by C1orf106 expression.