NCAPD2 promotes the malignant progression of oral squamous cell carcinoma via the Wnt/ß-catenin pathway.

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, with a poor prognosis, yet the underlying mechanism needs further exploration. Non-SMC condensin I complex subunit D2 (NCAPD2) is a widely expressed protein in OSCC, but its role in tumor development is unclear. This study aimed to explore NCAPD2 expression and its biological function in OSCC. NCAPD2 expression in OSCC cell lines and tissue specimens was analyzed using quantitative polymerase chain reaction, western blotting, and immunohistochemistry. Cancer cell growth was evaluated using cell proliferation, 5-Ethynyl-2'-deoxyuridine (EdU) staining, and colony formation assays. Cell migration was evaluated using wound healing and Transwell assays. Apoptosis was detected using flow cytometry. The influence of NCAPD2 on tumor growth in vivo was evaluated in a mouse xenograft model. NCAPD2 expression was significantly higher in OSCC than that in normal oral tissue. In vitro, the knockdown of NCAPD2 inhibited OSCC cell proliferation and promoted apoptosis. NCAPD2 depletion also significantly inhibited the migration of OSCC cells. Moreover, NCAPD2 overexpression induced inverse effects on OSCC cell phenotypes. In vivo, we demonstrated that downregulating NCAPD2 could inhibit the tumorigenicity of OSCC cells. Mechanically, OSCC regulation by NCAPD2 involved the Wnt/ß-catenin signaling pathway. These results suggest NCAPD2 as a novel oncogene with an important role in OSCC development and a candidate therapeutic target for OSCC.

Chemotherapy for primary cancer can reduce the risk of head and neck second primary malignancy: a propensity-matched analysis.

OBJECTIVES: To investigate the effect of chemotherapy versus no chemotherapy on the risk of second primary head and neck malignancies (SPHNMs) in patients with locally advanced oral squamous cell carcinoma (OSCC) and to assess the survival outcomes of patients with SPHNM. MATERIALS AND METHODS: A total of 937 OSCC patients were divided into chemotherapy and nonchemotherapy groups by propensity score matching (PSM). In the presence of the competing event of non-SPHNM death, the fine and gray modified Cox proportional hazard model was fitted to detect the impact of various factors, including the history of chemotherapy, on SPHNM risk. The Kaplan-Meier method was used to assess the survival outcomes of patients. RESULTS: After PSM, the 10-year cumulative probability of SPHNM was 10.7% for patients who received chemotherapy and 22.1% for patients who did not. The fine and gray regression model showed that prior chemotherapy was associated with a 51% reduced risk of SPHNM (adjusted subdistribution hazard ratio (sHR): 0.49, 95% confidence interval (CI): 0.29-0.84, P = 0.1). The disease-free survival (DFS) rates did not differ significantly between the SPHNM and non-SPHNM groups. And there were no significant differences in DFS rates between the patients with and those without prior chemotherapy in the SPHNM group. CONCLUSIONS: Chemotherapy for locally advanced primary OSCC is associated with a decreased incidence of subsequent SPHNM. However, chemotherapy for the primary cancer does not improve DFS in patients with SPHNM. CLINICAL RELEVANCE: Chemotherapy plays a positive role in preventing SPHNMs for patients with oral squamous cell carcinoma. CLINICAL TRIAL REGISTRATION: Before January 2015, the data were retrieved retrospectively, while after January 2015, the data were collected prospectively in a POROMS database (ClinicalTrials.gov ID: NCT02395367).

Establishment of an orthotopic transplantation model of tongue carcinoma.

OBJECTIVE: This study aims to establish an orthotopic transplantation model of rabbit tongue carcinoma and study its biological characteristics. METHODS: Tongue carcinoma was induced in purebred New Zealand white rabbits by exposure to 7,12-dimethylbenz[α]anthracene and mechanical stimulation. Fresh tumor tissues obtained from the induced tongue carcinoma model were then serially transplanted orthotopically into tongues of healthy rabbits. The tumor formation rate, invasion to surrounding tissues, regional lymph node metastases, and distant-organ metastases were investigated. Morphological observation by optical and electron microscopy, immunohistochemical examination, and chromosome analysis were performed. RESULTS: An orthotopic transplantation model of rabbit tongue carcinoma, designated as RSCC-2, was established. The tongue cancer was poorly differentiated squamous cell carcinoma. The tumor cell was hypotetraploid with a chromosome mode of 70. Immunohisto chemical examination showed positive staining for keratin. The tongue carcinoma survived in rabbits for 73 rounds of transplantation, using 465 rabbits in total. The average latent period was 12.5 days, and the average rabbit survival period was 37.5 days. The tumor formation rate was 10% to 20% in the first 20 rounds and increased gradually thereafter. After the 45th transplantation, the tumor formation rate and success rate of preservation in liquid nitrogen reached 100%. Regional lymph node metastases (35%) and lung metastases (20%) occurred after 50 rounds. In the advanced stage, tumors invaded the entire tongue. Animals suffered from weight loss and died of cachexia. CONCLUSIONS: RSCC-2 is the first animal model for orthotopical transplantation of primary tongue carcinoma. It successfully simulates the clinical pathological process of primary tongue cancer in human, provides invaluable insights into the pathogenesis and metastasis mechanisms, and can be useful for evaluating new therapeutics for the treatment of tongue cancer.