3.1 Clinical characteristics in head and neck squamous cell carcinoma (HNSCC) patients

Most patients were male (75%), with a mean age of 48.19 years. Among the study population, 104 patients received induction chemotherapy, and 81 completed the full treatment course. The follow-up duration was 94 months. The main tumor sites were the oropharynx (43.3%) and hypopharynx (30.8%), with varying grades. Most patients had an ECOG score of 0 (79.8%). The majority of the patients were diagnosed at Stage IV (92.3%), with T4N2 (25%) and T3N2 (14.4%) being common subcategories (Table 1).

Table 1 Overview of clinical characteristics in head and neck squamous cell carcinoma (HNSCC) patients3.2 Response to treatment3.2.1 Response to induction chemotherapy (104 patients)

Induction chemotherapy has demonstrated a high level of efficacy in treating advanced HNSCC. Among the patients treated, 16.4% achieved a complete response, while 36.5% showed a partial response. Additionally, 35.6% experienced stable disease, but unfortunately, 11.5% experienced disease progression. These results underscore the potential of induction chemotherapy in managing HNSCC (Table 2).

Induction Chemotherapy + Chemo-radiotherapy Response (88 patients):

Furthermore, the addition of radiotherapy to induction chemotherapy significantly improved treatment outcomes. The complete response rates increased to 59.1%, with 15.9% of patients achieving substantial partial responses. Disease stabilization was observed in 13.6% of patients, while 11.4% experienced disease progression (Table 2).

Table 2 Response rates and outcomes of induction chemotherapy and combined induction chemotherapy with radiotherapy in HNSCC treatment3.3 Outcomes of patients with head and neck squamous cell carcinoma (HNSCC)

Our analysis of the 88 patients who completed induction chemotherapy and concomitant chemoradiotherapy revealed the following outcomes. The majority of patients (59.1%, 52/88) who achieved a complete response (CR) stopped treatment after protocol completion. Among the 14 patients with a partial response (PR), a small subset (2 patients, 2.3% of the total cohort) refused the recommended conservative surgery. Of the 12 patients with stable disease (SD), two (2.3%) were not amenable to radical surgery, and another two (2.3%) died after concomitant chemoradiotherapy. Finally, for the 10 patients with progressive disease (PD), alternative treatment strategies—defined as therapies outside the standard protocol, including palliative chemotherapy, targeted therapy, or participation in clinical trials—were employed in 8 cases (9.1% of the total cohort) (Table 3).

Table 3 Outcomes of treatment head and neck squamous cell carcinoma (HNSCC)3.4 DPP7 as a potential diagnostic marker in HNSCC

The evaluation of DPP7 gene expression via qRT-PCR revealed a significant increase in HNSCC tissues compared to matched nearby normal tissues (NNT). The mean relative DPP7 expression (2−ΔCt) was 6.6 ± 1.2 in tumor tissues versus 2.5 ± 0.3 in normal controls (p < 0.0001), as shown in Fig. 1A.

Additionally, the evaluation of DPP7 levels in the serum of HNSCC patients and controls revealed a significant elevation in patients (11.49 ± 2.07) compared to controls (2.3 ± 0.3) (p < 0.0001), Fig. 1B.

The results of the ROC curve analysis demonstrate that DPP7 expression exhibits strong discriminatory capacity between HNSCC and normal tissues, with an AUC of 1.000, a p-value < 0.0001, and a 95% confidence interval of 1.000 to 1.000, all indicating statistically significant diagnostic performance. These findings suggest that DPP7 may serve as a potential biomarker for distinguishing HNSCC from normal tissues, which could have important clinical implications (Fig. 1C).

Similarly, the ROC curve analysis demonstrated strong discriminatory performance between HNSCC serum and control serum based on DPP7 expression, yielding an AUC of 1.000. The p-value of < 0.0001 and a 95% confidence interval of 1.000 to 1.000 indicate a statistically significant diagnostic accuracy for DPP7 in distinguishing between the two groups (Fig. 1D).

Our findings revealed a strong association between DPP7 expression in the tissues and serum of HNSCC patients. The Pearson correlation coefficient (r) was 0.9909, and the p-value of < 0.0001 confirms a statistically significant, strong positive correlation (Fig. 1E).

Fig. 1

Diagnostic and Prognostic performance of DPP7 as a biomarker for HNSCC

3.5 Prognostic significance of DPP7 in HNSCC: associations with patient characteristics

Table 4 summarizes the relationship between DPP7 expression in tumor tissues and patient serum with key clinicopathological features in HNSCC. DPP7 levels were significantly associated with several established prognostic factors.

Analysis of DPP7 levels in tissue samples revealed statistically significant differences across various demographic and clinical parameters (all p < 0.0001). DPP7 expression was significantly higher in older patients (> 50 years) compared to younger individuals (7.71 vs. 5.59). Statistically significant elevations were also observed in female patients compared to males (8.31 vs. 6.05) and in patients with a poor performance status (PS 1) compared to those with a good performance status (PS 0) (8.4 vs. 6.16). However, these latter findings regarding sex and performance status should be interpreted with caution, as the female (n = 26) and PS 1 (n = 21) subgroups were relatively small, and the analysis may be underpowered for these variables. Furthermore, DPP7 expression increased with worsening tumor differentiation, rising from 5.07 in well-differentiated tumors to 8.07 in poorly-differentiated tumors. Patients with advanced stage IV disease exhibited higher DPP7 levels compared to those with stage III disease (6.77 vs. 4.7).

Identical trends were observed in serum DPP7 levels, with all comparisons reaching statistical significance (p < 0.0001). This consistency between tissue and serum samples indicates that DPP7 may serve as a reliable circulating biomarker for the non-invasive monitoring of disease status.

Table 4 Relationship between DPP7 expression and clinicopathological factors in HNSCC3.6 Evaluation of DPP7 expression as a biomarker for treatment response in HNSCC

DPP7 expression was analyzed in relation to treatment response in HNSCC patients (Fig. 2). In tumor tissues, a significant stepwise increase in DPP7 levels was observed with worsening clinical outcome, from lowest in patients with a complete response (CR) to highest in those with progressive disease (PD) (p < 0.0001, Fig. 2A). A highly similar pattern was found in serum samples, where DPP7 concentrations also increased progressively across response categories (CR to PD, p < 0.0001, Fig. 2B).

Together, these findings suggest an association between elevated DPP7 expression and poorer treatment response and prognosis. Furthermore, the consistent pattern observed in serum indicates that circulating DPP7 could serve as a non-invasive biomarker for predicting therapeutic efficacy and monitoring disease outcome in HNSCC.

Fig. 2

DPP7 Expression in HNSCC Tissues (A) and Serum (B) Stratified by Clinical Response to Treatment (CR: Complete Response, PR: Partial Response, SD: Stable Disease, PD: Progressive Disease)

3.7 Univariate and multivariate analysis of DPP7 as a prognostic biomarker in HNSCC

Univariate analysis revealed significant correlations between DPP7 expression in tumor tissues and key prognostic factors in HNSCC (Table 5). DPP7 levels increased significantly with patient age (p < 0.0001) and were higher in females than in males (p < 0.0001). Furthermore, DPP7 expression demonstrated a strong positive association with advancing disease stage (Stage IV vs. Stage III, p < 0.0001) and showed progressively higher levels with worsening tumor grade (p < 0.0001). These findings support the role of DPP7 as a valuable prognostic biomarker for risk stratification in HNSCC.

Table 5 Univariate analysis of DPP7 expression correlation with prognostic factors in head and neck squamous cell carcinoma (HNSCC)

The multivariate analysis confirms that DPP7 is an independent prognostic marker in head and neck squamous cell carcinoma (HNSCC) (Table 6). Even after adjusting for other factors, DPP7 shows strong associations with important disease characteristics. Specifically, DPP7 levels increase with age (p < 0.0001), women have higher DPP7 levels than men (p < 0.0001), DPP7 levels rise with tumor undifferentiation (p < 0.0001), and patients with advanced Stage IV disease have higher DPP7 levels than those in Stage III (p < 0.0001). These findings establish DPP7 as a significant independent prognostic biomarker in HNSCC, and its strong connections to adverse clinicopathological features underscore its potential to improve risk stratification and inform personalized treatment strategies.

Table 6 Multivariate analysis of DPP7 as an independent prognostic marker in head and neck squamous cell carcinoma3.8 DPP7 expression and survival in HNSCC patients

The overall and disease-free survival analyses provide compelling evidence that HNSCC prognosis is powerfully dictated by DPP7 expression status. Both the log-rank and Gehan-Breslow-Wilcoxon tests demonstrate the survival curves are highly statistically distinct between high and low DPP7 groups (p < 0.005 for both) (Fig. 3).

The survival disparities are staggering. Median overall survival was just 23.74 months for patients with high tumor DPP7, compared to an impressive 67.82 months in the low DPP7 cohort (Fig. 3A). Similarly, the median disease-free survival was 23.74 months in the high DPP7 group versus 66.03 months for low DPP7 - an over 2.7-fold difference (p < 0.001 for both) (Fig. 3B).

Fig. 3

Survival in HNSCC patients according to DPP7 Expression