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  • br The present data showed that


    The present data showed that CCR4 was highly ex-pressed in some patients with pN0 oral tongue cancer. CCR4 Biotin-tyramide exhibited undetectable to overex-pression levels in oral cancer tissues, and its expres-sion level in human primary tongue tumor tissues was considerably higher than that in normal human oral mucosa. The authors speculated that CCR4 could promote the progression of oral cancers at an early stage. When focused on TSCC, the most common can-cer in the oral cavity, CCR4 expression was statistically associated with a higher pathologic tumor stage, and patients with CCR4-positive expression had a poorer prognosis than those with CCR4-negative expression. Further analysis showed that CCR4 was an indepen-dent prognostic factor for patients’ OS.
    In the authors’ previous work, similar observations were recorded for pN0 gastric cancer, in which CCR4 expression was positively associated with tumor stage and could promote gastric cancer cell invasion by upregulation of matrix metallopeptidase-9.18 These results are consistent with the fact that some other chemokine receptors, such as CXCR4, CCR7, and CCR10, also are involved in tumor invasion.22-26 Furthermore, the present findings highlight the pivotal role of CCR4 in tumor progression at a relatively early stage of oral cancer development
    FIGURE 2. Prognostic relevance assessed using Kaplan-Meier analysis and log-rank tests. A, B, Patients with tongue squamous cell carcinoma and positive chemokine (C-C motif) receptor-4 expression (+, ++, +++) had a poorer prognosis for overall and disease-free survival than patients with negative chemokine (C-C motif) receptor-4 expression. C, D, Overall and disease-free survival of patients with tongue squamous cell car-cinoma decreased as the level of chemokine (C-C motif) receptor-4 expression increased. Abbreviations: , Negative immunoreactivity; +, weak immunoreactivity; ++, moderate immunoreactivity; +++, strong immunoreactivity.
    Wang et al. CCR4 Expression in pN0 Oral Tongue Cancer. J Oral Maxillofac Surg 2019.
    compared with lymph node metastasis. Cell invasion is the first step of cancer metastasis that has dramatic effects on the survival of patients with cancer. In this study, the authors hypothesized that CCR4 in pN0 tongue cancer tissues might promote tumor invasion and progression and thus act as a novel biomarker for poor prognosis in pN0 oral tongue cancer. The present findings on the relation between CCR4 expression and patient survival are similar to those of another chemokine receptor, CCR7, which could be involved in tumor progression and act as an indicator of lymphatic metastatic recurrence in patients with pN0 esophageal cancer.27 Detection at the molecular level could help predict tumor behavior and could be better than confirmation by only histo-logic characteristics.28 The present results indicated 
    that CCR4 might mediate the potential for cancer cells to invade and metastasize along a continuous disease course and could be used as a poor prognostic indica-tor in patients with pN0 oral tongue cancer. It could provide additional prognostic information to further inform management when making difficult decisions, because TSCC is a heterogeneous disease and patients with the same stage and grade can have completely different clinical outcomes.29-33
    The strength of the present study is the finding that CCR4 was highly expressed in pN0 oral tongue cancer, which could be used to control early events in tumor progression by using antagonists of CCR4. The limita-tion is that patients were recommended to receive adjuvant therapies according to the National Compre-hensive Cancer Network Clinical Practice Guidelines
    Univariate Analysis
    Multivariate Analysis
    Parameters Categories HR (95% CI) P Value
    Abbreviations: CCR4, chemokine (C-C motif) receptor-4; CI, confidence interval; DFS, disease-free survival; HR, hazard ratio; OS, overall survival.
    Wang et al. CCR4 Expression in pN0 Oral Tongue Cancer. J Oral Maxillofac Surg 2019.
    in Oncology, but the influences of postoperative adju-vant therapies on the prognosis of patients with TSCC were not investigated. Thus, future studies also should evaluate whether the altered expression of CCR4 is involved in adjuvant therapies.
    In conclusion, the authors found that the expression of CCR4 in oral tongue cancer tissues was markedly higher than that in normal tongue tissues and was posi-tively correlated with tumor stage and poor prognosis of patients with pN0 TSCC, thus highlighting its poten-tial as a prognostic biomarker and potential therapeu-tic target in oral tongue cancer.