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Secretory Leukocyte Protease Inhibitor in Oral Potentially Malignant Disorders and Oral Squamous Cell Carcinoma

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Secretory Leukocyte Protease Inhibitor in Oral Potentially Malignant Disorders and Oral Squamous Cell Carcinoma Published online: 2021-06-03 Original Article Secretory Leukocyte Protease Inhibitor in Oral Potentially Malignant Disorders and Oral Squamous Cell Carcinoma Abstract Vidya Ajila1, Objectives: Secretory leukocyte protease inhibitor (SLPI) is a protein found in body fluids and Subhas Babu1, implicated as a prognostic factor in many cancers. There is limited research regarding serum Veena Shetty2, and salivary SLPI in oral potentially malignant disorders (OPMDs) and oral squamous cell 1 carcinoma (OSCC). Materials and Methods: A total of 90 participants were included in the study; Shruthi Hegde , 3 of which 30 formed the control group, 30 included participants with OPMD, and 30 included Shilpa Shenoy participants with OSCC. Serum and salivary levels of SLPI were estimated using enzyme‑linked 1Department of Oral Medicine immunosorbent assay. Results: Serum levels of SLPI showed progressive increase in potentially and Radiology, A. B. Shetty malignant disorders and SCC patients when compared with controls, while salivary levels were Memorial Institute of Dental increased in both OPMD and OSCC groups as compared to controls. However, the difference Sciences, Nitte Deemed to be University, 2Department of between groups was not statistically significant (P < 0.05). Conclusion: The above results suggest Microbiology, K. S. Hegde that increase in SLPI levels in the serum may have a role in indicating progression of OPMD to Medical Academy, Nitte Deemed OSCC. to be University, 3Central Research Laboratory, K. S. Keywords: Oral potentially malignant disorders, oral squamous cell carcinoma, saliva, Secretory Hegde Medical Academy, leukocyte protease inhibitor, serum Nitte Deemed to be University, Mangalore, Karnataka, India Introduction pancreatic islets, epithelial cells investing the renal tubules, acinar cells of parotid Oral cancer is the 15th most prevalent and submandibular glands, acinar cells of cancer worldwide with a 50% survival submucosal glands, and epithelial cells rate despite recent advances in surgery, lining mucous membranes of respiratory chemotherapy and radiotherapy.[1] More and alimentary tracts. SLPI protects the than 95% of oral cancers are squamous cell tissues by inhibiting proteases such as carcinomas (SCCs).[2] The high incidence cathepsin G, elastase, and trypsin from of oral cancer in India is attributed to the neutrophils; chymotrypsin; and trypsin habits of tobacco chewing and smoking. from pancreatic acinar cells and chymase These carcinogens interact with the and tryptase from mast cells. The main oral mucosa to cause premalignant and action is inhibition of neutrophil elastase Submitted: 05‑Apr‑2018 malignant changes. Most malignancies which protects epithelial surfaces from Revised: 18‑May‑2018 of the oral cavity arise from preexisting Accepted: 21‑Jun‑2018 damage.[3] Initially studied for its role in the premalignant lesions.[1] With a view to Published: 17‑Feb‑2020 prevention of HIV transmission in saliva, prevention of oral potentially malignant SLPI has recently been recognized as a disorders (OPMD) developing into oral Address for correspondence: potential diagnostic and prognostic marker SCCs (OSCCs), various studies have tried Dr. Vidya Ajila, in the head‑and‑neck cancer.[4] It is found to identify biomarkers in the serum and Department of Oral Medicine in most secretions of the body and mainly and Radiology, A. B. saliva. in saliva.[5] Previous research on SLPI has Shetty Memorial Institute of Dental Sciences, Nitte Secretory leukocyte protease inhibitor used brush biopsy specimens in OPMD Deemed to be University, [6] (SLPI) was first isolated from secretions and OSCC. This report demonstrated a Mangalore, Karnataka, India. of patients with chronic obstructive significant decrease in SLPI in participants E‑mail: [email protected] pulmonary disease and cystic fibrosis with oral precancer and cancer with the and was thereby considered a major anti levels decreasing progressively from oral elastase inhibitor. SLPI is produced by precancer to cancer. A recent study has Access this article online neutrophils, macrophages, beta‑cells of evaluated archived salivary samples of Website: www.ijmpo.org patients who went on to develop OSCC and DOI: 10.4103/ijmpo.ijmpo_75_18 found that high salivary SLPI in smokers Quick Response Code: This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, How to cite this article: Ajila V, Babu S, Shetty V, as long as appropriate credit is given and the new creations are Hegde S, Shenoy S. Secretory leukocyte protease licensed under the identical terms. inhibitor in oral potentially malignant disorders and oral squamous cell carcinoma. Indian J Med Paediatr Oncol 2019;40:491-5. For reprints contact: [email protected] © 2020 Indian Journal of Medical and Paediatric Oncology | Published by Wolters Kluwer - Medknow 491 Ajila, et al.: Secretory leukocyte protease inhibitor was associated with increased risk of the head‑and‑neck SCCs (HNSCC).[5] However, studies which have evaluated serum and salivary SLPI in OPMD and OSCC are lacking. The present study aims to evaluate the role of serum and salivary SLPI in progression of OPMD into OSCC. Materials and Methods A total of 90 participants reporting to the outpatient department of our institute were included in the study. They were divided into three groups of 30 participants each: Group I included participants diagnosed with OPMD, Figure 1: Graph showing the habits associated with oral potentially Group II included participants diagnosed with OSCC, malignant disorders. Gutkha chewing was the most common etiologic agent and Group III formed the control group. Participants with in oral submucous fibrosis while smoking was associated with leukoplakia any underlying systemic disease were excluded from the study. Institutional Ethics Committee Clearance and written Salivary Secretory leukocyte protease inhibitor informed consent were obtained from each study participant. The mean level of SLPI in the control, OPMD, and OSCC Demographic data were acquired from the participants groups were 80.28, 103.60, and 92.76 pg/ml, respectively. and were followed by an examination of the oral cavity. The difference between the groups was statistically Venous blood was withdrawn from the antecubital vein and nonsignificant [Figure 5]. serum obtained. Whole saliva was collected by asking the participants to allow saliva to collect in the mouth and then Discussion spit into sterile containers every minute for 5 min. Saliva SLPI is an 11.7 kDa highly basic nonglycosylated and serum were stored at − 20° until analysis. protein. SLPI contributes to host mucosal defense of oral, Serum and salivary SLPI was determined using nasopharyngeal, genital, and respiratory tissues. Salivary [7] ELISA (Hycult Laboratories, Netherlands). The results SLPI was initially studied for its anti‑HIV activity. obtained were subjected to statistical analysis. Studies have shown a protective function for SLPI against [8] human papillomavirus (HPV) infection of the oral cavity. Statistical analysis It has a major role in protecting tissues against the harmful [3] Kruskal–Wallis test was used to compare the three effects of inflammation. It also has bactericidal and [3] groups. Intergroup comparison was done using Mann– fungicidal properties. Even though the anti‑HIV property Whitney U‑test. Correlation analysis was performed using of SLPI is well established, there appears to be no role for [3] Spearman’s correlation test. SLPI in other retroviral infections. Recently, SLPI is being investigated for its role in a variety Results of cancers such as ovarian, breast, colorectal, pancreatic, and [6,9‑13] Of the 30 participants with OPMD (study Group 1), oral cancer. It has been implicated in cancer progression [13] [14] 26 were male and 4 were female. The third, fourth, and metastasis. Cordes et al. demonstrated that lower and fifth decades all had equal number of cases. Oral SLPI was associated with metastatic HNSCC. Devoogdt [15] submucous fibrosis (OSMF) was the most common lesion et al. studied the role of SLPI in lung tumor progression in this group followed by leukoplakia and erosive lichen and found that SLPI had definite promalignant activity. planus [Figure 1]. Gutkha chewing was the most common The authors concluded that this property of SLPI was due etiologic agent in OSMF, while smoking was associated to its protease inhibiting activity rather than its property of [15] [13] with leukoplakia. Study Group II (OSCC) consisted of increasing cell proliferation. Zhang et al. proved that 24 males and 6 females. Maximum cases were seen in the elevated SLPI in pancreatic adenocarcinoma was associated [13] 7th decade followed by the 6th decade. The most common with cell proliferation and growth of tumor. Decreased SLPI is believed to promote spread of the tumor by allowing site was the buccal mucosa followed by the tongue and [8] the alveologingival sulcus [Figure 2]. Betel‑quid chewing degradation of tissues by proteases produced by tumor cells. (BLAT) was the most common associated etiological Quabius et al.[16] found that decreased SLPI was associated factor [Figure 3]. with HPV‑induced OSCC, while smoking‑induced OSCC had higher levels of SLPI and absence of HPV positivity. Serum Secretory leukocyte protease inhibitor Quabius et al.[16] proposed that SLPI protects against The mean level of SLPI
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