Oral squamous cell carcinoma (OSCC) is a highly aggressive cancer and the fourth leading malignancy among males in Taiwan. Some pathogenic bacteria are associated with periodontitis and oral cancer. ...However, the comprehensive profile of the oral microbiome during the cancer's progression from the early stage to the late stage is still unclear. We profiled the oral microbiota and identified bacteria biomarkers associated with OSCC. The microbiota of an oral rinse from 51 healthy individuals and 197 OSCC patients at different stages were investigated using 16S rRNA V3V4 amplicon sequencing, followed by bioinformatics and statistical analyses. The oral microbiota communities from stage 4 patients showed significantly higher complexity than those from healthy controls. The populations also dynamically changed with the cancer's progression from stage 1 to stage 4. The predominant phyla in the oral samples showed variation in the relative abundance of
, and
. The abundance of
increased significantly with the progression of oral cancer from the healthy controls (2.98%) to OSCC stage 1 (4.35%) through stage 4 (7.92%). At the genus level, the abundance of
increased, while the number of
, and
decreased with cancer progression.
, and
were associated with OSCC, and they progressively increased in abundance from stage 1 to stage 4. The abundances of
, and
were inversely associated with OSCC progression. We selected a bacterial marker panel of three bacteria (upregulated
, down-regulated
, and
), which had an AUC of 0.956 (95% CI = 0.925-0.986) in discriminating OSCC stage 4 from the healthy controls. Furthermore, the functional prediction of oral bacterial communities showed that genes involved in carbohydrate-related metabolism, such as methane metabolism, and energy-metabolism-related parameters, such as oxidative phosphorylation and carbon fixation in photosynthetic organisms, were enriched in late-stage OSCC, while those responsible for amino acid metabolism, such as folate biosynthesis and valine, leucine, and isoleucine biosynthesis, were significantly associated with the healthy controls. In conclusion, our results provided evidence of oral bacteria community changes during oral cancer progression and suggested the possibility of using bacteria as OSCC diagnostic markers.
Background
Biomarkers in head and neck squamous cell carcinoma (HNSCC) emerge rapidly in recent years, especially for new targeted therapies and immunotherapies.
Methods
Recent, relevant ...peer‐reviewed evidence were critically reviewed and summarized.
Results
This review article briefly introduces essential biomarker concepts, including purposes and classifications (predictive, prognostic, and diagnostic markers), and the phases of biomarker development. We summarize current biomarkers in order of clinical utility; p16 and human papillomavirus status remain the most important and validated biomarkers in HNSCC. The rationale for biomarker study design continues to evolve with technological advances, especially whole‐exome or whole‐genomic sequencing. Noninvasive body fluid and liquid biopsy biomarkers appear to hold strong potential for development as tools for early cancer detection, cancer diagnosis, monitoring of disease recurrence, and outcome prediction. In light of discrepancies among different technologies, standardized approaches are needed.
Conclusion
Biomarkers from cancer tissue or blood in HNSCC could direct new anticancer therapies.
Head and neck cancer (HNC) is one of the 10 most frequent cancers worldwide, with an estimated over 500 000 new cases being diagnosed annually. The overall 5‐year survival rate in patients with HNC ...is one of the lowest among common malignant neoplasms and has not significantly changed during the last two decades. Oral cavity squamous cell carcinoma (OSCC) shares part of HNC and has been reported to be increasing in the betel quid chewing area in recent years. During 2006, OSCC has become the sixth most common type of cancer in Taiwan, and it is also the fourth most common type of cancer among men. It follows that this type of cancer wreaks a high social and personal cost. Environmental carcinogens such as betel quid chewing, tobacco smoking and alcohol drinking have been identified as major risk factors for head and neck cancer. There is growing interest in understanding the relationship between genetic susceptibility and the prevalent environmental carcinogens for HNC prevention. Within this review, we discuss the molecular and cellular aspects of HNC carcinogenesis in Taiwan, an endemic betel quid chewing area. Knowledge of molecular carcinogenesis of HNC may provide critical clues for diagnosis, prognosis, individualization of therapy and molecular therapeutics. (Cancer Sci 2008; 99: 1507–1514)
Purpose
This study evaluates serial radiographic changes in the maxillary sinus of patients with oral cancer after an inferior maxillectomy and a soft tissue free flap reconstruction.
Methods
...Fifty‐six patients were evaluated between Oct 2005 and Mar 2017 from an institutional database. Preoperative and surveillance imaging was reviewed at set time‐points. Maxillary sinus scores were allotted based on a modification of the Lund–MacKay staging system. Patients were evaluated for change in sinus score. A univariate (UV) and multivariate (MV) analysis was performed.
Results
There were 53.5% T3/T4 category tumors and 68% received adjuvant treatment. Median follow‐up was 24.4 months. Preoperative mean sinus score was 0.27 ± 0.44 and postoperative mean sinus score at 24 months was 1.2 ± 1.3 (p = <0.001). On UV analysis advanced T‐stage at 12 months (OR 6.7, 95% CI 1.2–50.3, p = 0.01) and 24 months (OR 5.2, 95% CI 1.03–36.8, p = 0.04) was associated with significantly higher sinus score. On MV analysis, advanced T‐stage continued to be associated with increased odds for higher sinus score (OR 4.9, 95% CI 1.1–26.8, p = 0.039).
Conclusion
A mild increase in postoperative sinus score is seen in this cohort of patients. Advanced T‐stage is associated with increased odds for higher sinus scores.
Background
We aimed to probe the hemoglobin–albumin–lymphocyte–platelet (HALP) score's prognostic value in oral cavity squamous cell carcinoma (OSCC).
Methods
Medical data of 350 patients with ...primary operated OSCC were retrospectively reviewed. We derived the optimal HALP cutoff by executing receiver operating characteristic curve analysis, and patients were then grouped based on this cutoff value. Cox proportional hazards model were used to discover survival outcome‐associated factors.
Results
We derived the optimal HALP cutoff as 35.4. A low HALP score (<35.4) predicted poorer overall and disease‐free survival (hazard ratio: 2.29 and 1.92, respectively; both p < 0.001) and was significantly associated with OSCC aggressiveness. We established a HALP‐based nomogram that accurately predicted overall survival (concordance index: 0.784).
Conclusion
The HALP score may be a useful prognostic biomarker in patients with OSCC undergoing surgery, and the HALP‐based nomogram can be a promising prognostic tool in clinical setting.
Background
We aimed to investigate whether depth of invasion (DOI) should be an independent indication for postoperative radiotherapy (PORT) in small oral squamous cell carcinomas (SCC).
Methods
...Retrospective analysis of DOI (<5, 5 to <10, ≥10 mm) and disease‐specific survival (DSS) in a multi‐institutional international cohort of 1409 patients with oral SCC ≤4 cm in size treated between 1990‐2011.
Results
In patients without other adverse factors (nodal metastases; close <5 mm or involved margins), there was no association between DOI and DSS, with an excellent prognosis irrespective of depth. In the absence of PORT, the 5‐year disease‐specific mortality was 10% with DOI ≥10 mm, 8% with DOI 5‐10 mm, and 6% with DOI <5 mm (P = .169), yielding an absolute risk difference of only 4%.
Conclusion
The deterioration in prognosis with increasing DOI largely reflects an association with other adverse features. In the absence of these, depth alone should not be an indication for PORT outside a clinical trial.
Background
This study aimed to explore the prognostic utility of the preoperative platelet‐to‐albumin ratio (PAR) among patients with oral cavity squamous cell carcinoma (OSCC).
Methods
We ...retrospectively reviewed of 355 patients with surgically‐treated OSCC between 2008 and 2017. The optimal PAR cutoff for patient stratification was determined through X‐tile analysis. Prognostic variables for disease‐free survival (DFS) and overall survival (OS) were identified using Cox proportional hazards models. We developed a PAR‐based nomogram to predict personalized OS.
Results
We determined the optimal PAR cutoff to be 7.45. A PAR of ≥7.45 was an independent negative prognostic factor for DFS and OS (hazard ratio = 1.748 and 2.386; p = 0.005 and p < 0.001, respectively). The developed nomogram demonstrates the practical utility of PAR and accurately predicts personalized OS.
Conclusions
The preoperative PAR is a promising and cost‐effective prognostic biomarker for patients with surgically‐treated OSCC; the PAR‐based nanogram accurately predicts OS for such patients.
MicroRNAs offer tools to identify and treat invasive cancers. Using highly invasive isogenic oral squamous cell carcinoma (OSCC) cells, established using in vitro and in vivo selection protocols from ...poorly invasive parental cell populations, we used microarray expression analysis to identify a relative and specific decrease in miR-491-5p in invasive cells. Lower expression of miR-491-5p correlated with poor overall survival of patients with OSCCs. miR-491-5p overexpression in invasive OSCC cells suppressed their migratory behavior in vitro and lung metastatic behavior in vivo. We defined the G-protein-coupled receptor kinase-interacting protein 1 (GIT1)-as a direct target gene for miR-491-5p control. GIT1 overexpression was sufficient to rescue miR-491-5p-mediated inhibition of migration/invasion and lung metastasis. Conversely, GIT1 silencing phenocopied the ability of miR-491-5p to inhibit migration/invasion and metastasis of OSCC cells. Mechanistic investigations indicated that miR-491-5p overexpression or GIT1 attenuation reduced focal adhesions, with a concurrent decrease in steady-state levels of paxillin, phospho-paxillin, phospho-FAK, EGF/EGFR-mediated extracellular signal-regulated kinase (ERK1/2) activation, and MMP2/9 levels and activities. In clinical specimens of OSCCs, GIT1 levels were elevated relative to paired normal tissues and were correlated with lymph node metastasis, with expression levels of miR-491-5p and GIT1 correlated inversely in OSCCs, where they informed tumor grade. Together, our findings identify a functional axis for OSCC invasion that suggests miR-491-5p and GIT1 as biomarkers for prognosis in this cancer.
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