Archives of Oral Biology
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To build a prognostic model for oral squamous cell carcinoma patients with type 2 diabetes mellitus.
Oral squamous cell carcinoma patients with type 2 diabetes mellitus in Xiangya Hospital were studied. Patients during January 2011 to January 2015 were included in training set (n=146), and those during January 2017 to December 2020 were included in test set (n=81). Univariate and multivariate Cox regressions were used to screen independent prognostic variables. Nomogram was used to show the model. C-index, internal bootstrap resampling and external validation were used to evaluate the model.
Six independent prognostic factors (T stage, N stage, pathological grade, metformin use, sulfonylureas use, and fasting blood glucose) were screened from training set. Based on the six variables, nomogram was constructed to predict the prognosis of oral squamous cell carcinoma patients with type 2 diabetes mellitus. C-index value was 0.728, and result of internal bootstrap resampling showed better prediction efficiency for one-year survival. All patients were divided into two groups according to total points calculated based on the model. Group with low total points experienced better survival than that with high total points both in training set and test set.
The model provides a relatively accurate method to predict the prognosis of oral squamous cell carcinoma patients with type 2 diabetes mellitus.
Oral squamous cell carcinoma (OSCC), the most common type of oral cancer, accounts for 90% of all cancer types in oral cavity (Warnakulasuriya, 2009). In the past several years, new cases of oral cancer have been growing rapidly. According to the global cancer statistic, the number of new cases of 2020 is 22,849 more than that of 2018 (Bray et al., 2018; Sung et al., 2021). Patients diagnosed with early stage of OSCC usually experience a better 5-year survival rate (90%), while the 5-year survival rate of those diagnosed with later stage drops sharply to 30% (Omar, 2015). Researchers have developed many tools to predict the survival of OSCC patients. The most well-known one to us is the TNM staging system(Moeckelmann et al., 2018). According to the size of primary tumor, lymph node metastasis and distant metastasis, the prognosis of patients with OSCC can be preliminarily predicted. However, some other clinical factors can also affect the prognosis of patients with OSCC. Wang et al. constructed a prognostic model of OSCC based on clinicopathological data including age, sex, site, race, origin, grade, surgery, radiation and TNM stage (Wang et al., 2018). Nomograms of the model allowed clinicians to predict the long-term survival rate of OSCC patients more accurately.
Type 2 diabetes mellitus (T2DM), a complex chronic systemic disease, is charactered by insulin resistance and deficiency in insulin secretion, accounting for 95% diabetes mellitus patients(Xu et al., 2018). According to the prediction of the International Diabetes Federation (IDF), the population of diabetic patients will grow from 382 million in 2013–592million in 2035 by 55% (Shi & Hu, 2014). T2DM is closely related to the occurrence and development of various oral diseases. It was reported that T2DM and periodontitis could promote each other, T2DM could increase the risk of periodontitis by 34%, and the prevalence of T2DM was significantly higher in periodontitis patients(Wu et al., 2020). Some infectious diseases, such as oral candidiasis, could also be secondary to uncontrolled T2DM(Sampath et al., 2019). Diabetes is also closely related to OSCC. Referring to the statistics of Xiangya Hospital in China, OSCC patients accompanying with T2DM account for 14.3% of all OSCC patients (Hu et al., 2020). Predictably, this proportion will continue to increase as the number of people with T2DM increases. In our previous study, type 2 diabetes mellitus (T2DM) was an independent risk factor for OSCC patients (Hu et al., 2020). Thus, OSCC patients with T2DM a special population with unique prognostic characteristics. However, up to now, there has not been a prognostic model for OSCC patients with T2DM.
In this study, we aimed to construct a model that could predict the prognosis of OSCC patients with T2DM. The model will allow clinicians to relatively accurately predict the prognosis of patients based on their clinical and pathological characteristics, thereby assisting in determining treatment plans.
The training cohort of OSCC patients with T2DM during January 2011 to January 2015 of Xiangya Hospital presented in previous study were used to construct the prognostic model (Hu et al., 2020). Study design, sample size calculation, inclusion and exclusion criteria had been described in detail previously. OSCC patients diagnosed with T2DM in their past history and final diagnosis were included in this study. Squamous cell carcinoma located at “tongue”, “buccal mucosa”, “gingiva”, “floor of the
In total, 146 OSCC patients with T2DM were used to construct the prognostic model. The follow-up time ranged from the lowest 10 days to the highest 1825 days, with a mean follow up of 1186.82 days (standard error, 62.25). Among all variables, missing values were found in 8 variables including urban and rural residence (2.1%), education level (9.6%), tobacco use (0.7%), alcohol consumption (2.1%), betel quid chewing (2.1%), pathological grade (6.2%), fasting blood glucose (8.2%) and HbA1c
T2DM and cancer are becoming increasingly prevalent all over the world. More and more studies show that T2DM can increase the incidence rate of cancer(Shlomai et al., 2016). In T2DM patients, the prevalence of oral cancer was 0.25%, and patients with oral cancer combined with diabetes mellitus experienced a higher mortality than controls(Ramos-Garcia et al., 2021). A comparative study in Taiwan, China, conducted by Tseng CH, showed that metformin could decrease oral cancer risk in patients with
In conclusion, we constructed a prognostic model for predicting the prognosis of OSCC patients with T2DM by 6 clinicopathological factors, including T stage, N stage, pathological grade, metformin use, sulfonylureas use and fasting blood glucose level. As some controllable factors, we suggest that OSCC patients with T2DM should strictly control their blood glucose in a relatively normal range, and give priority to the metformin use to control T2DM without affecting the efficacy. Finally,
This work was supported by the National Natural Science Foundation , Project of National Center for Clinical Medical Research of Geriatrics [2021LNJJ08], and Hunan Postgraduate Scientific Research Innovation Project (key project) [CX20220118].
CRediT authorship contribution statement
Xin Hu: the conception and design of the study, acquisition of data, analysis and interpretation of data, drafting the article or revising it critically for important intellectual content, final approval of the version to be submitted. Haofeng Xiong: acquisition of data, analysis and interpretation of data, drafting the article or revising it critically for important intellectual content, final approval of the version to be submitted. Shiying Huang: the conception and design of the study,
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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- S. Patil
Metformin treatment decreases the expression of cancer stem cell marker CD44 and stemness related gene expression in primary oral cancer cells
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The global implications of diabetes and cancer
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Metformin and sulfonylureas in relation to cancer risk in type II diabetes patients: a meta-analysis using primary data of published studies
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- S. Warnakulasuriya
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Metformin inhibits proliferation of oral squamous cell carcinoma cells by suppressing proteolysis of nerve growth factor receptor
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Does three-dimensional intraglandular location predict malignancy in parotid tumors?
International Journal of Oral and Maxillofacial Surgery, Volume 52, Issue 3, 2023, pp. 296-303
Tumors arising within the parotid encompass a heterogeneous mix of benign and malignant neoplasms and other tissue growths. The purpose of this study was to determine the association between the location of intraparotid masses and the risk of malignancy. A retrospective cohort study was performed of patients diagnosed with parotid tumors following open tumor excision. The primary predictor variable was the location of the epicenter of the tumor in three-dimensional space, as determined from preoperative imaging. Other variables were patient demographics and clinical parameters. The primary outcome variable was the final histopathologic diagnosis of a benign or malignant process. A χ2 analysis was performed to test for any significant associations between demographic, clinical, and radiographic factors in relation to the outcome, and backwards stepwise logistic regression analysis was used to control for variables. Both increasing age (P=0.002) and the presence of local pain (P=0.020) were associated with malignancy. Tumors located anterior to the posterior border of the retromandibular vein had 2.18 times higher odds of malignancy (95% confidence interval 1.13–4.21; P=0.020). Multivariate regression analysis suggested that patient age, the presence of pain, and tumor location anterosuperiorly and superoinferiorly could all assist in determining the odds of malignancy.
An alternative way for fronto-orbito-zygomatic reconstruction in congenital malformations: A case report with 4-year follow-up
Journal of Stomatology, Oral and Maxillofacial Surgery, Volume 123, Issue 4, 2022, pp. e224-e227
Cdc42 regulates cranial suture morphogenesis and ossification
Biochemical and Biophysical Research Communications, Volume 512, Issue 2, 2019, pp. 145-149
Cdc42 (cell division cycle 42) is ubiquitously expressed small GTPases belonging to the Rho family of proteins. Previously, we generated limb bud mesenchyme-specific Cdc42 inactivated mice (Cdc42 conditional knockout mice; Cdc42 fl/fl; Prx1-Cre), which showed short limbs and cranial bone deformities, though the mechanism related to the cranium phenotype was unclear. In the present study, we investigated the role of Cdc42 in cranial bone development. Our results showed that loss of Cdc42 caused a defect of intramembranous ossification in cranial bone tissues which is related to decreased expressions of cranial suture morphogenesis genes, including Indian hedgehog (Ihh) and bone morphogenetic proteins (BMPs). These findings demonstrate that Cdc42 plays a crucial role in cranial osteogenesis, and is controlled by Ihh- and BMP-mediated signaling during cranium development.
Is a Medical Degree Associated With Faculty Leadership Position Attainment in Oral and Maxillofacial Surgery Residency Programs?
Journal of Oral and Maxillofacial Surgery, Volume 80, Issue 12, 2022, pp. 2024-2028
The decision to obtain double-degree versus single-degree training in oral and maxillofacial surgery (OMS) has been a widely debated topic in the United States over the past several decades. The purpose of this study is to determine if OMS faculty holding leadership positions (ie, program directors and chairs/chiefs) are more likely to be single-degree trained versus double-degree trained.
The authors designed a cross-sectional observational study to address the research purpose. The primary predictor variable was faculty leadership education (single-degree trained vs double-degree trained). The secondary predictor variable was accredited OMS program type led by the faculty with leadership positions (double-degree, both single-degree and double-degree, single-degree, or military program). The primary outcome variable was faculty leadership position (program director or chair/chief). Sums and percentages were calculated and Chi-squared (χ2) tests were used to compare the faculty leadership education with faculty leadership positions for each group. P values less than .05 were considered statistically significant.
The study sample was composed of 198 subjects, of which 99 subjects were identified as program directors and 99 subjects were identified as chairs/chiefs. There was no statistically significant difference between the proportions of program directors and chairs/chiefs who were single-degree trained versus double-degree trained when looking at all accredited OMS programs in the United States (52.5% vs 47.5%, P=.615 and 56.6% vs 43.4%, P=.191, respectively). However, program directors of double-degree programs were statistically significantly more likely to be double-degree trained than single-degree trained (77.1% vs 22.9%, P=.001) and program directors and chairs/chiefs of single-degree programs were statistically significantly more likely to be single-degree trained than double-degree trained (67.4% vs 32.6%, P=.022 and 65.1% vs 34.9%, P=.047, respectively).
Overall, no statistically significant difference exists between the proportions of program directors and chairs/chiefs that were single-degree trained versus double-degree trained at accredited OMS programs. However, when stratifying programs by program type, program directors of double-degree programs were statistically significantly more likely to be double-degree trained and program directors and chairs/chiefs of single-degree programs were statistically significantly more likely to be single-degree trained.(Video) SQUAMOUS CELL CARCINOMA PART-1 ( BENIGN AND MALIGNANT TUMORS OF ORAL CAVITY)
RELAXIN enhances differentiation and matrix mineralization through Relaxin/insulin-like family peptide receptor 2 (Rxfp2) in MC3T3-E1 cells in vitro
Bone, Volume 65, 2014, pp. 92-101
RELAXIN (RLN) is a polypeptide hormone of the insulin-like hormone family; it facilitates birth by softening and widening the pubic symphysis and cervix in many mammals, including humans. The role of RLN in bone metabolism was recently suggested by its ability to induce osteoclastogenesis and activate osteoclast function. RLN binds to RELAXIN/INSULIN-LIKE FAMILY PEPTIDE 1 (RXFP1) and 2 (RXFP2), with varying species-specific affinities. Young men with mutated RXFP2 are at high risk for osteoporosis, as RXFP2 influences osteoblast metabolism by binding to INSULIN-LIKE PEPTIDE 3 (INSL3). However, there have been no reports on RLN function in osteoblast differentiation and mineralization or on the functionally dominant receptors for RLN in osteoblasts. We previously described Rxfp1 and 2 expression patterns in developing mouse oral components, including the maxillary and mandibular bones, Meckel's cartilage, tongue, and tooth primordia. We hypothesized that Rln/Rxfp signaling is a key mediator of skeletal development and metabolism. Here, we present the gene expression patterns of Rxfp1 and 2 in developing mouse calvarial frontal bones as determined by in situ hybridization. In addition, RLN enhanced osteoblastic differentiation and caused abnormal mineralization and extracellular matrix metabolism through Rxfp2, which was predominant over Rxfp1 in MC3T3-E1 mouse calvarial osteoblasts. Our data suggest a novel role for Rln in craniofacial skeletal development and metabolism through Rxfp2.
Nuclear import of transcriptional corepressor BCOR occurs through interaction with karyopherin α expressed in human periodontal ligament
Biochemical and Biophysical Research Communications, Volume 507, Issues 1–4, 2018, pp. 67-73
Mutations in the gene encoding BCL-6 corepressor (BCOR) are responsible for oculofaciocardiodental (OFCD) syndrome, which is a rare X-linked dominant disorder characterized by radiculomegaly of permanent teeth as the most typical symptom. To function as a transcriptional corepressor, BCOR needs to enter the nucleus; however, the molecular pathway for its nuclear translocation during dental root formation remains unclear. The purpose of this study was to determine the mechanism underlying BCOR transport into the nucleus. Our results showed that human periodontal ligament (PDL) cells expressed karyopherin α (KPNA)2, KPNA4, and KPNA6 belonging to a family of nuclear import proteins, which interacted with BCOR in the immunoprecipitation assay. Site-directed mutagenesis targeting the two nuclear localization signals (NLSs) within BCOR reduced its nuclear translocation; however, co-expression of KPNA2, KPNA4, or KPNA6 with BCOR carrying a previously described mutation which eliminated one of the two NLSs significantly increased nuclear accumulation of the mutant BCOR, indicating participation of KPNA in BCOR nuclear translocation. Comparative expression profiling of PDL cells isolated from normal and OFCD patients revealed significant downregulation of SMAD4, GLI1, and nuclear factor 1-C (NFIC) mRNA expression, suggesting that BCOR mutations cause hyperactive root formation in OFCD syndrome by inhibiting SMAD4-Hedgehog-NFIC signaling implicated in dental root development. Our study contributes to understanding of the mechanisms providing nuclear import of BCOR during root formation.
ORCID: 0000-0002-5257-0051(Video) Squamous cell carcinoma | Oral Path | The Dentistry Girl |
© 2023 Elsevier Ltd. All rights reserved.
Tumor grade (p=0.007), tumor thickness (p=0.012), and LVI (p=0.0003) also predicted for distant recurrence. Nodal stage is a stronger clinical prognosticator for survival and recurrence in oral SCC than patient or tumor factors including tumor stage, bone invasion, and type of bone resection.What is the prognosis for oral squamous cell carcinoma? ›
Prognosis for Oral Squamous Cell Carcinoma
For localized carcinoma of the floor of the mouth, 5-year survival is 75%. Lymph node metastasis decreases survival rate by about half. Metastases reach the regional lymph nodes first and later the lungs. For lower lip lesions, 5-year survival is 90%, and metastases are rare.
Tumor expression of miR-448 is a prognostic marker in oral squamous cell carcinoma | BMC Cancer | Full Text.Can diabetes cause squamous cell carcinoma? ›
Squamous cell carcinoma (SCC) is one of the most common cancers worldwide. Additionally, diabetes mellitus (DM) is a high prevalent comorbidity and the amount of patients with DM is expected to significantly increase. Recent studies have found an increased risk of developing SCC in patients with DM.Which squamous cell carcinoma has best prognosis? ›
Patients with stage I, II, or III cancer have the best survival, whereas patients with stage IV or recurrent cancer who are older than 66.5 years have the worst survival. Patients with stage IV or recurrent cancer who are younger than 66.5 years have intermediate survival.What is the prognostic significance of Ki 67 positivity in oral squamous cell carcinoma? ›
The Ki-67 expression is significantly higher in tissues with moderately –differentiated or poorly differentiated squamous cell carcinoma and moderate or severe Oral epithelial dysplasia and provides an objective criterion for determining the severity of OED and histological grading of OSCC.What are the prognostic indicators? ›
A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease or the chance of the disease recurring (coming back).What are examples of prognostic markers? ›
Examples of prognostic biomarkers are PSA level at the time of a prostate cancer diagnosis or the PIK3CA mutation status of tumors in women with human epidermal growth factor receptor 2 (HER2) –positive metastatic breast cancer.What are the prognostic factors influencing the survival difference of oral tongue squamous cell carcinoma? ›
For oral tongue squamous cell carcinoma, radiotherapy was a good prognostic factor. On the contrary, a tumor with large vertical size, closed surgical margin, poor histologic grade, and radical neck dissection in the operated group were poor prognostic factors.Which patient is at highest risk for squamous cell carcinoma? ›
Age over 50: Most SCCs appear in people over age 50. Fair skin: People with fair skin are at an increased risk for SCC. Gender: Men are more likely to develop SCC. Sun-sensitive conditions including xeroderma pigmentosum.
The risk of aggressive squamous cell carcinoma of the skin may be increased in cases where the cancer: Is particularly large or deep. Involves the mucous membranes, such as the lips.What organs does squamous cell carcinoma spread to? ›
If left untreated, squamous cell carcinoma can spread to nearby lymph nodes, bones or distant organs (such as the lungs or liver). Normal squamous tissue usually appears flat. When this tissue develops cancer it can appear as round masses that are can be flat, raised, or ulcerated.How many years does it take for squamous cell carcinoma to spread? ›
Metastasis of cutaneous squamous cell carcinoma (cSCC) is rare. However, certain tumor and patient characteristics increase the risk of metastasis. Prior studies have demonstrated metastasis rates of 3-9%, occurring, on average, one to two years after initial diagnosis .Is oral squamous cell carcinoma aggressive? ›
Tongue squamous cell carcinoma is one of the most aggressive tumours in behaviour. Even at early stages may the patient need to be submitted to a treatment plan consisting of radio/chemotherapy besides surgical removal of the tumour (31).Is squamous cell carcinoma in mouth curable? ›
Small changes to the DNA of the squamous cells make the cells grow abnormally. These mutated cells accumulate, forming a tumor that grows in the mouth and often spread to lymph nodes in the neck. Oral cancer is curable if detected at an early stage.What is the most important risk factor for squamous cell carcinoma? ›
Most squamous cell carcinomas of the skin result from prolonged exposure to ultraviolet (UV) radiation, either from sunlight or from tanning beds or lamps. Avoiding UV light helps reduce your risk of squamous cell carcinoma of the skin and other forms of skin cancer.What is the most important prognostic factor? ›
The most important prognostic factor in all human cancers is the stage at presentation, which is the anatomic extent of the disease.What features are important in the prognosis of carcinoma? ›
Some of the factors that affect prognosis include: The type of cancer and where it is in your body. The stage of the cancer, which refers to the size of the cancer and if it has spread to other parts of your body. The cancer's grade, which refers to how abnormal the cancer cells look under a microscope.