Using SCC Antigen and CRP Levels as Prognostic Biomarkers in Recurrent Oral Cavity Squamous Cell Carcinoma

<div><p>Squamous cell carcinoma antigen (SCC-Ag) and C-reactive protein (CRP) levels have been successfully used to stratify risk groups in primary oral squamous cell carcinoma (OSCC) patients; however, related biomarkers have rarely been investigated in recurrent OSCC. The purpose of the present study was to analyze the relationships of SCC-Ag and CRP levels at the time of recurrence with clinical factors and prognosis. We retrospectively recruited patients with recurrence in a cohort of 534 OSCC patients between March 2001 and July 2013. One hundred patients had recurrence. The serum SCC-Ag and CRP levels were measured at the time of cancer diagnosis, 3 to 6 months after treatment with clinical disease-free, and at the time of recurrence. The SCC-Ag levels were significantly lowered after treatment (paired t-test: p = 0.001) and re-elevated at the time of recurrence (paired t-test: p = 0.027). An SCC-Ag level ≥2.0 ng/ml and a CRP level ≥5.0 mg/L at the time of recurrence were significantly associated with recurrent tumor status (P<0.001), recurrent nodal metastasis (χ² trend test: P = 0.020), distant metastasis (P<0.001), and overall survival (P<0.001). Moreover, the influence of both elevated SCC-Ag and CRP levels on overall survival (P<0.001, H.R. [95% CI]: 5.406 [2.210–13.222]) still existed after adjusting for the recurrent tumor stage and patient age. The present study demonstrates that concurrent high levels of both SCC-Ag and CRP at the diagnosis of recurrence acts as a predictor of recurrent tumor status, recurrent advanced tumor stage, distant metastasis, and survival after the diagnosis of recurrence. This study expands the applicability of these two markers in the risk stratification in recurrent OSCC.</p></div

Multivariate Cox regression model of prognostic covariates in 100 patients with oral cavity squamous cell carcinoma regarding their disease-free and overall survival.

<p>HR, hazard ratio; CI, confidence interval.</p>a<p>stages I and II, ^bstages III, IVa, IVb, and IVc.</p><p>OS, overall survival.</p

Univariate log-rank test of prognostic covariates in 100 patients with oral cavity squamous cell carcinoma regarding their overall survival after the diagnosis of recurrence.

<p>CRP (−), CRP level <5.0 mg/L; CRP (+), CRP level ≥5.0 mg/L; SCC-Ag (−), SCC-Ag <2.0 ng/ml; SCC-Ag (+), SCC-Ag ≥2.0 ng/ml.</p

Association of CRP and SCC-Ag levels at the time of recurrence (N = 100).

<p>^*Fisher's exact test.</p

Survival curves in 100 recurrent OSCC patients related to the CRP and SCC-Ag levels.

<p>The low CRP and low SCC-Ag group showed significantly better OS compared to the high CRP and high SCC-Ag group (P<0.001).</p

Survival curves in 100 recurrent OSCC patients according to (A) CRP level (log rank test, P<0.001) and (B) SCC-Ag level (log-rank test, P = 0.001).

<p>Survival curves in 100 recurrent OSCC patients according to (A) CRP level (log rank test, P<0.001) and (B) SCC-Ag level (log-rank test, P = 0.001).</p

Additional file 1: of Roles of preoperative C-reactive protein are more relevant in buccal cancer than other subsites

Clinical information of 343 OSCC patients. (SAV 100 kb

Pre-Treatment Levels of C-Reactive Protein and Squamous Cell Carcinoma Antigen for Predicting the Aggressiveness of Pharyngolaryngeal Carcinoma

<div><p>The levels of squamous cell carcinoma antigen (SCC-Ag) and C-reactive protein (CRP) can be used to predict tumor invasion, lymph node metastasis, staging and survival in patients with oral cavity cancer. The present study analyzed the relationship between pre-treatment levels of SCC-Ag and CRP in relation to clinicopathological factors in patients with pharyngolaryngeal cancer (PLC) and determined whether elevated levels of CRP and SCC-Ag were associated with tumor metabolic activity via [18F] fluorodeoxyglucose positron emission tomography (FDG-PET). We retrospectively recruited one hundred and six PLC patients between June 2008 and December 2011. All patients received computed tomography (CT)/magnetic resonance imaging (MRI) and FDG-PET staging analyses, and the serum levels of SCC-Ag and CRP in these patients were measured prior to treatment. A SCC-Ag level ≥2.0 ng/ml and a CRP level ≥5.0 mg/L were significantly associated with clinical stage (P<0.001), clinical tumor status (P<0.001), and clinical nodal status (P<0.001). The elevation of both SCC-Ag and CRP levels was correlated with the standardized uptake value (SUV) max of the tumor (≥8.6 mg/L) and lymph nodes (≥5.7 ng/ml) (P = 0.019). The present study demonstrated that the presence of high levels of both pre-treatment SCC-Ag and CRP acts as a predictor of clinical stage, clinical tumor status, and clinical nodal status in patients with PLC. Moreover, elevated levels of SCC-Ag and CRP were associated with a high metabolic rate as well as the proliferative activity measured according to the SUVmax of the tumor and lymph nodes. Therefore, elevated levels of these two factors have the potential to serve as biomarkers for the prediction of tumor aggressiveness in cases of PLC.</p> </div

Characteristics of the 106 pharyngolaryngeal carcinoma patients.

*<p>SD: Standard deviation.</p

The associations between preoperative SUVtumor-max/SUVnodal-max and CRP/SCC-Ag (n = 106).

<p>Abbreviation: CRP: C-reactive protein;SCC-Ag: squamous cell carcinoma antigen; SUVtumor-max: maximum standardized uptake valve in tumor; SUVnodal-max: maximum standardized uptake valve in lymph nodes.</p><p>CRP (−): CRP level <5.0 mg/L; CRP (+): CRP level ≥5.0 mg/L; SCC-Ag (−): SCC-Ag <2.0 ng/ml; SCC-Ag (+): SCC-Ag ≥2.0 ng/ml.</p><p>SUVtumor-max (−): SUVtumor-max level <8.6 mg/L; SUVtumor-max (+): SUVtumor-max level ≥8.6 mg/L; SUVnodal-max (−): SUVnodal-max <5.7 ng/ml; SUVnodal-max (+): SUVnodal-max ≥5.7 ng/ml.</p>*<p>Chi-square test.</p