Stoichioproteomics study of differentially expressed proteins and pathways in head and neck cancer

Hypoxia is a prominent feature of head and neck cancer. However, the oxygen element characteristics of proteins and how they adapt to hypoxia microenvironments of head and neck cancer are still unknown. Human genome sequences and proteins expressed data of head and neck cancer were retrieved from pathology atlas of Human Protein Atlas project. Then compared the oxygen and carbon element contents between proteomes of head and neck cancer and normal oral mucosa-squamous epithelial cells, genome locations, pathways, and functional dissection associated with head and neck cancer were also studied. A total of 902 differentially expressed proteins were observed where the average oxygen content is higher than that of the lowly expressed proteins in head and neck cancer proteins. Further, the average oxygen content of the up regulated proteins was 2.54% higher than other. None of their coding genes were distributed on the Y chromosome. The up regulated proteins were enriched in endocytosis, apoptosis and regulation of actin cytoskeleton. The increased oxygen contents of the highly expressed and the up regulated proteins might be caused by frequent activity of cytoskeleton and adapted to the rapid growth and fast division of the head and neck cancer cells. The oxygen usage bias and key proteins may help us to understand the mechanisms behind head and neck cancer in targeted therapy, which lays a foundation for the application of stoichioproteomics in targeted therapy and provides promise for potential treatments for head and neck cancer.

Clinical Review and Management of Oral Potentially Malignant Disorders with Epithelial Dysplasia

Background: Oral potentially malignant disorders (OPMDs) comprise any disorders, tumors, in addition to any microscopic alterations that have a risk of malignant development of cancers of the mouth. When epithelial dysplasia is detected in an oral lesion, it is termed as a precancerous lesion. Finding: Several changes in the color or thickness of normal oral mucosa might be detected during the clinical diagnosis of the oral lesions. Leukoplakia of the oral cavity is a clinical name for one of the most predominant OPMDs of the oral mucosa. When comparing oral examination with naked eyes to planning to apply staining with special stain or using an image of optical fluorescence, the incidence of patients with oral epithelial dysplasia may rise, as well as the clearing of the lesion boundary. Increased size of more than 2cm2, the presence of colored regions with a red hue, the presence of lichenoid process characteristics, and severe epithelial dysplasia are all considered risk factors. One-third of premalignant lesions may progress to cancer, whereas the other two-thirds may stay stable or regress without progressing to malignancy. Conclusion: It is critical to research the patients' unique characteristics, which include psychological, genetic, dietary, and dental problems. When epithelial dysplasia is present in an oral lesion, it is termed a precancerous lesion. Oral potential malignant diseases with epithelial dysplasia may or may not develop into carcinoma and may or may not be recurrent.

Expression of Ki-67, Cornulin and ISG15 in non-involved mucosal surgical margins as predictive markers for relapse in oral squamous cell carcinoma (OSCC)

Background Local relapse of oral squamous cell carcinoma in non-involved mucosal surgical margins indicated possibility of field alteration in the margins, which could be predicted with certain biomarkers. The objectives were to evaluate the expression of Ki-67, Cornulin and ISG15 in non-involved mucosal surgical margins and the association of clinicopathological prognosticators with local relapse in oral squamous cell carcinoma. Methods Surgical margins from the study (relapse) group (n = 23), control (non-relapse) group (n = 32) and normal oral mucosa (n = 5) were immunohistochemically stained using Ki-67, Cornulin and ISG15 antibodies. Association between expression of markers and clinicopathological prognosticators with local relapse in oral squamous cell carcinoma was analyzed statistically. Results The study group surgical margins demonstrated significantly decreased Cornulin expression (p = 0.032). Low Cornulin expression was significantly associated with local relapse (p = 0.004) and non-tongue primary tumor (p = 0.013). Although not significantly associated with local relapse, expression of Ki-67 was significantly reduced in female patients (p = 0.041). Age above 57.5 years, Chinese & Indian ethnicity, alcohol consumption, epithelial dysplasia in surgical margins, and type III and IV patterns of invasion of tumor were also significantly related to local relapse. Regression analysis showed low expression of Cornulin (p = 0.018), and increased patient’s age (p = 0.008) were predictors of local relapse in oral squamous cell carcinoma, with 34-fold risk and 18-fold risk, respectively. Expression of Ki-67 and ISG15 did not show significant association with local relapse in oral squamous cell carcinoma. Conclusion Low expression of Cornulin is an independent predictor of relapse in oral squamous cell carcinoma.

Diagnostic Value of Cytokeratin 17 during Oral Carcinogenesis: An Immunohistochemical Study

Background. Little is known about the role of cytokeratin 17 (CK17) during oral carcinogenesis. CK17 expression in oral leukoplakia (OL), the most encountered oral potentially malignant disorders and oral squamous cell carcinoma (OSCC), remains very limited. To determine the role of CK17 during oral carcinogenesis and its potential diagnostic marker in oral premalignant and malignant lesions, this study evaluated CK17 expression in OL without dysplasia, OL with dysplasia, and OSCC. CK17 expression in these tissues was compared with those of normal oral mucosa (NOM). Additionally, the relationship between CK17 expression and clinicopathologic factors of OSCC was investigated. Methods. CK17 expression was evaluated in 186 samples consisting of 12 NOM, 33 OL without dysplasia, 58 OL with dysplasia, and 83 OSCC using immunohistochemistry. The proportion of positively immunostained cells was evaluated and scored. Results. CK17 was expressed in 8.3%, 54.5%, 74.1%, and 90.4% of NOM, OL without dysplasia, OL with dysplasia, and OSCC, respectively. NOM had a significantly lower CK17 score than OL with dysplasia ( p = 0.0003 ) and OSCC ( p < 0.0001 ). A significant association between CK17 expression and histopathologic differentiation of OSCC was found. Tumors with well differentiation had high CK17 expression compared with those of moderate and poor differentiation. Conclusion. CK17 was overexpressed in OL with dysplasia and OSCC, suggesting that CK17 plays a pivotal role in the development of premalignant lesions and OSCC. Of clinical significance, CK17 may be a good diagnostic marker for oral premalignant lesions and OSCC. Additionally, CK17 could be used as an objective tool to classify histopathologic grade in OSCC. The findings that CK17 expression is high in OSCC but low in NOM imply that CK17 may serve as a potential therapeutic target for OSCC.

Downregulation of Lipid Phosphate Phosphatase 3 correlates with Tumor-Infiltrating Immune Cells in Oral Cancer

Purpose Sphingosine-1-phosphate (S1P), a potent oncogenic lipid. Intracellular levels of S1P are tightly regulated by eight S1P metabolizing enzymes. S1P is synthesized by phosphorylation of sphingosine which is catalyzed by two sphingosine kinases (SphK1 and SphK2). Five lipid phosphatases (two S1P phosphatases and three lipid phosphate phosphatases) reversibly convert S1P back to sphingosine. S1P is ultimately irreversibly degraded by S1P lyase. The role of sphingosine-1-phosphate (S1P) metabolizing enzymes in oral squamous cell carcinoma (OSCC) has not been fully studied. Methods In the current study, we have determined the protein expression of four S1P metabolizing enzymes, namely sphingosine Kinase (SphK) -1, SphK2, S1P phosphatase 1 (SGPP1), and lipid phosphate phosphatase 3 (LPP3) by immunohistochemistry (IHC) and western botting in tumor tissues of 46 OSCC patients and normal oral mucosa (N = 6). Further, we determined the associations of expression of S1P metabolizing enzymes with clinicopathological features of OSCC patients. Results SphK2 and LPP3 exhibit low IRS in OSCC tumors. Importantly, expression of SphK2 and LPP3 was downregulated in malignant cells compared to non-malignant mucosa. Further, LPP3 expression negatively correlated with TNM staging of patients (ρ = -0.307, p = 0.043). Importantly, TCGA analysis revealed that LPP3 expression was positively correlated with infiltration of B cells, neutrophils, macrophages, and dendritic cells in the HNSCC tumors. Conclusion In conclusion, our data show that expression of SphK2 and LPP3 is decreased in OSCC tumors compared to normal mucosa. Thus, LPP3 could represent a potential prognostic marker and therapeutic target for OSCC.

Ki-67 expression in human oral squamous cell carcinoma

Oral cancers are one of the 10 leading cancers in the world. However, in India, it is one of the most common cancers and constitutes a major public health problem. Oral squamous cell carcinoma is a well-known malignancy that accounts for more than 90% of all oral cancers. The study is carried out on 40 biopsy samples received on oral mucosa, in Department of Pathology of our institute. Maximum numbers of patients were from 3th to 6th decade in our study. 38 cases of oral squamous cell carcinoma were observed, out of which 31 (81.57%) were male, and 07 (18.42%) cases were female. The most common site was tongue (50%), followed by buccal mucosa (18.42%), 06 patients (15.78%) had lesion at palate. Thirty-five (92.10%) cases had a significant history of tobacco use/smoking, whereas 03 (7.89%) did not have any history of tobacco use. We observed Ki-67 LI for normal oral mucosa was 14 ± 5.6%. In well-differentiated carcinoma, the KI-67 LI was 28.52 ± 21.25%, which increased to 42.85 ± 18.2% in moderately differentiated carcinoma and 68.57 ± 17.6% in poorly differentiated carcinoma. Ki-67 acts as an excellent marker of cellular proliferation. There is a statistical difference in KI-67 overexpression between various grades of oral squamous cell carcinoma and normal oral mucosa (p value &#60;0.05).

Clinical Review and Management of Oral Potentially Malignant Disorders with Epithelial Dysplasia

Background: Oral potentially malignant disorders (OPMDs) comprise any disorders, tumors, in addition to any microscopic alterations that have a risk of malignant development of cancers of the mouth. When epithelial dysplasia is detected in an oral lesion, it is termed as a precancerous lesion. Finding: Several changes in the color or thickness of normal oral mucosa might be detected during the clinical diagnosis of the oral lesions. Leukoplakia of the oral cavity is a clinical name for one of the most predominant OPMDs of the oral mucosa. When comparing oral examination with naked eyes to planning to apply staining with special stain or using an image of optical fluorescence, the incidence of patients with oral epithelial dysplasia may rise, as well as the clearing of the lesion boundary. Increased size of more than 2cm2, the presence of colored regions with a red hue, the presence of lichenoid process characteristics, and severe epithelial dysplasia are all considered risk factors. One-third of premalignant lesions may progress to cancer, whereas the other two-thirds may stay stable or regress without progressing to malignancy. Conclusion: It is critical to research the patients' unique characteristics, which include psychological, genetic, dietary, and dental problems. When epithelial dysplasia is present in an oral lesion, it is termed a precancerous lesion. Oral potential malignant diseases with epithelial dysplasia may or may not develop into carcinoma and may or may not be recurrent.

Expression of Interleukin-1ß and Interleukin-8 in Oral Potentially Malignant Disorders and Carcinomas

Objective: To evaluate interleukin-1ß (IL-1ß) and interleukin-8 (IL-8) epithelial expressions in potentially malignant disorders of the oral mucosa as malignant predictive markers.Study design: About 55 tissues embedded in paraffin, comprising 15 oral lichen planus (OLP) lesions, 15 leukoplakias, 15 oral squamous cell carcinomas (OSCC), and 10 samples of normal oral mucosa were included in the study. IL-1ß and 8 expressions were assessed by immunohistochemistry using antibodies antihuman IL-1ß human (sc-7884, Santa Cruz® H-153) and antihuman IL-8 (ab7747, abcam®). The number of positive cells was compared using Student's t-test. Any p-value &lt; 0.05 was considered statistically significant.Results: Nuclear and cytoplasmatic keratinocyte staining were positive for both cytokines in all study groups. However, a statistically significant decrease was observed within all cases compared to normal mucosa, both staining for IL-1β and 8. Moreover, IL-8 showed significant differences between OLP and leukoplakia, and when compared to OSCC.Conclusions: Oral epithelial expression of IL-1β and 8 seems to decrease when the malignant transformation of the oral mucosa increases.