Association of DOK3 and infiltrated tumor-associated macrophages with risk for the prognosis of Porphyromonas gingivalis-infected oral cancer: a 12-year data analysis of 200 patients from a tertiary teaching hospital, Urumqi, China.

BACKGROUND: While there is an understanding of the association between the expression of Porphyromonas gingivalis (P. gingivalis) and prognosis of oral squamous cell carcinoma (OSCC), significance specially to address the relevance between different immunohistochemical intensities of P. gingivalis and tumor-associated macrophages (TAMs) in OSCC tissue and related clinicopathologic characteristics has not been well investigated. The present study aimed to investigate the pathological features related to M2-TAM in P. gingivalis-infected OSCC and ascertain its clinical relevance with patients' prognosis. METHODS: A prospective cohort study was designed to comparatively analyze 200 patients from June 2008 to June 2020. Bioinformatics analyses were implemented to identify DOK3 as a key molecule and to appraise immunocyte infiltration using Gene Expression Omnibus and The Cancer Genome Atlas databases. Immunohistochemical evaluation was performed to analyze the association between the expression levels of P. gingivalis, DOK3, and M2-TAM and clinicopathological variables using Fisher's exact test or Pearson's chi-square test. Cox analysis was used to calculate hazard ratios (HR) with corresponding 95% confidence interval (CI) for various clinicopathological features. The Kaplan-Meier approach and log-rank test were used to plot the survival curves. RESULTS: The expression level of P. gingivalis was positively associated with DOK3 and M2-TAMs expression level (P < 0.001). Parameters, including body mass index, clinical stage, recurrence, tumor differentiation, and P. gingivalis, DOK3, and M2-TAM immunoexpression levels, affected the prognosis of patients with OSCC (all P < 0.05). In addition, P. gingivalis (HR = 1.674, 95%CI 1.216-4.142, P = 0.012), DOK3 (HR = 1.881, 95%CI 1.433-3.457, P = 0.042), and M2-TAM (HR = 1.649, 95%CI 0.824-3.082, P = 0.034) were significantly associated with the 10-year cumulative survival rate. CONCLUSIONS: Elevated expression of P. gingivalis and DOK3 indicates M2-TAM infiltration and unfavorable prognosis of OSCC, and could be considered as three novel independent risk factors for predicting the prognosis of OSCC.

Effect of Prognostic Factors of Postoperative Radiotherapy in Oral Squamous Cell Carcinoma: A SEER-Based Study.

Objective: The treatment of oral squamous cell carcinoma (OSCC) is dominated by surgery and radiochemotherapy, but its prognosis is still unsatisfactory, with around five tenths of 5-year survival. This study aimed to assess the prognosis of OSCC patients treated with surgery with and without postoperative radiotherapy. Study Design: Retrospective study. Methods: The clinicopathological information and follow-up datasets on patients with OSCC (T1-4 and/or N+) registered from 2010 to 2015 were downloaded from the Surveillance, Epidemiology, and End Results database. Totally 7231 enrolled subjects were divided into a case group (surgery alone, n = 4167) and a control group (surgery combined with postoperative radiotherapy, n = 3064). One-to-one matching was performed by propensity score matching to make the baseline data comparable between the 2 subgroups. Multivariate Cox regression analysis was used to calculate hazard ratios (HR) of various clinicopathological features. The Kaplan-Meier method and log-rank test were used to plot the survival curves. Results: The majority of patients in case group were tumor stage I (n = 2569, 61.7%), whereas most patients in control group were stages III to IV (n = 2360, 77.1%). In the case group, the 1-, 3-, and 5-year overall survival (OS; 76%, 59.5%, 53.7%) were significantly lower than those of the control group (85.1%, 64.1%, 55.8%; P < .0001). Similarly, the 1-, 3-, and 5-year cancer-specific survival (CSS) of the case group (80.2%, 66.6%, 63.3%) were significantly lower than those of the control group (87.2%, 69.3%, 63.9%, respectively; P < .0001). Cox multivariate analysis indicated that age, differentiation, clinical stage, and tumor-node-metastasis stage affected the prognosis of OSCC patients, while postoperative radiotherapy was a protective factor (OS: HR = 0.649, P < .001; CSS: HR = 0.702, P < .001). Conclusions: Postoperative radiation was an independent protective factor, hence, the combination of surgery plus radiotherapy is more beneficial for the survival of patients with OSCC, particularly for advanced cases.

A radiobiological perspective on radioresistance or/and radiosensitivity of head and neck squamous cell carcinoma.

Background: This article aimed to compile and summarize clinically relevant literature in radiation therapy, and to discuss the potential in radioresistant and radiosensitive head and neck cancer. Study Design: Narrative review. Materials and methods: Google Scholar, PubMed and the Cochrane Library were retrieved using combined key words such as "radiotherapy" and "head and neck cancer". Search strings additionally queried were "radioresistant", "radiosensitive", "head and neck region", "squamous cell carcinoma", in combination with Boolean Operators 'AND' and 'OR'. Subsequently, the resulting publications were included for review of the full text. Results: Radiotherapeutic response currently in clinical observation referred to HNSCC scoping were selected into this review. The compiled mechanisms were then detailed concerning on the clinical significance, biological characteristics, and molecular function. Conclusions: Brachytherapy or/and external-beam radiotherapy are crucial for treating HNSCC, especially the early stage patients, but in patients with locally advanced tumors, their outcome with radiation therapy is poor due to obvious radioresistance. The curative effects mainly depend on the response of radiation therapy, so an updated review is needed to optimize further applications in HNSCC radiotherapy.