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. 2022 Oct 12;12(10):1458.
doi: 10.3390/biom12101458.

FDCSP Is an Immune-Associated Prognostic Biomarker in HPV-Positive Head and Neck Squamous Carcinoma

Qingqing Wu  1 , Tingru Shao  1 , Guangzhao Huang  2 , Zenan Zheng  1 , Yingtong Jiang  3 , Weisen Zeng  4 , Xiaozhi Lv  1
Affiliations

FDCSP Is an Immune-Associated Prognostic Biomarker in HPV-Positive Head and Neck Squamous Carcinoma

Qingqing Wu et al. Biomolecules. .

Abstract

Background: Head and neck squamous carcinoma (HNSC) poses a major threat to human life. The role of human papillomavirus (HPV) infection in the initiation and progression of HNSC is becoming more widely accepted. HPV-positive (HPV+) HNSC has shown unique responses to cancer therapies, which may be due to differences in immune cell infiltration. It is critical to determine how the immune responses to HPV in HNSC are regulated. Methods: Transcriptome data of HNSC from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database were analyzed. Then, the CIBERSORT algorithm was used to calculate immune cell infiltration in HNSC. FDCSP expression level was detected by qPCR in the HNSC tissues collected from the Nanfang Hospital. Results: Follicular dendritic cell secreted protein (FDCSP) was highly expressed in HPV+ HNSC, and higher expression of FDSCP was associated with a favorable prognosis. In HPV+ HNSC samples, FDCSP significantly increased the proportion of T follicular helper cells (TFHs). FDCSP expression was also found to be associated with TP53 mutation status in HPV+ HNSC. The function of FDCSP was intimately connected to chemokine pathways, particularly with the C-X-C motif chemokine ligand 13 (CXCL13). We verified that the high expression of FDCSP in HPV+ HNSC and higher FDCSP is closely related to prognosis in HNSC samples we collected by qPCR. Conclusions: Collectively, these findings may provide fresh evidence that FDCSP is a potential chemokine-associated prognostic biomarker in HPV+ HNSC.

Keywords: CIBERSORT; CXCL13; FDCSP; HPV; TP53; head and neck squamous carcinoma (HNSC) TCGA; immune cell infiltration.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Screening of HPV-related differential genes using the GEO database. (A) Venn diagram for GEO datasets. (B) Volcano map of differentially expressed genes in HPV+ verse HPV− group. (FDR < 0.05, fold change = 2). (C) Heatmap of differentially expressed genes, clustered by HPV status.
Figure 2
Figure 2
Overall survival analysis of DEGs in HPV status in HNSC. (A–D): Kaplan–Meier curves associated with upregulated differential genes (FDCSP, FAM3B, KRT19, NEFH) grouped by HPV status.
Figure 3
Figure 3
The relationship between FDCSP and immune cells in HNSC. (A) Expression of FDCSP in HSNC (from Timer2.0 database, grouped by HPV status, A z-score >5 suggests that the gene is expressed in that tissue). (B) FDCSP expression in human normal tissues. (C) Correlation between FDCSP expression and immune cell types in TCGA-HNSC cohorts (CIBERSORT_ABS). (D) Correlation between FDCSP expression and immune cell types of HNSC in GEO cohorts (CIBERSORT_ABS). (x-axis: Spearman Correlation(r), y-axis: -log10(p), Dotted line as dividing line: x at 0 and y at 1.301). *: p value<0.05, ***: p value<0.005.
Figure 4
Figure 4
The relationship between FDCSP and immune cells in TCGA-HNSC. (A–D) Kaplan–Meier curves for the corresponding immune infiltrates and FDCSP expression in HPV status. ((A) FDCSP in HPV+ with CD8 + T cells; (B) FDCSP in HPV− with CD4 + T cells; (C) FDCSP in HPV+ with TFHs; (D) FDCSP in HPV− with TFHs).
Figure 5
Figure 5
Variation in gene mutation frequency with FDCSP in HNSC.
Figure 6
Figure 6
Correlation between FDCSP and TP53 in HNSC. (A) Correlation between FDCSP and TP53 expression (Spearman). (B) Violin plot and boxplot showed correlation of FDCSP with mutated/wild-type (WT) TP53, Wilcoxon algorithm was used for calculating statistical difference.
Figure 7
Figure 7
Enrichment analysis of FDCSP. (A) GO enrichment. (B) GO biological processes. (C) GO cellular components. (D) GO molecular functions. (E) KEGG. (F) GSEA of KEGG.
Figure 8
Figure 8
Analysis of FDCSP-related genes. (A) Heatmap of differential genes in the high/low FDCSP group in GEO-HNSCs (50/159 DEGs is shown). (B) String PPI network and Venn diagram of DEGs and PPIs. Correlation of FDCSP and CXCL13 in HPV+/− HNSC in GEO cohorts. (C) FDCSP and CXCL13 mRNA expression in oropharyngeal cancer samples versus paired normal tissues. (D) FDCSP and CXCL13 protein expression in oropharyngeal cancer samples (3 HPV+ and 3 HPV− samples). (E) FDCSP mRNA expression relates with prognosis in oropharyngeal cancer samples (low group/L: FDCSP expression less than the median and high group/H: FDCSP expression more than the median).
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