Possible role for interleukins as biomarkers for mortality and recurrence in oral cancer

Abstract

Abstract:Objectives: Salivary and serum levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) have previously been studied in oral cancer with conflicting results. Methods: We designed a controlled study to assess the correlation between pretreatment salivary and serum levels of IL-6 and IL-8, and all-cause survival and cancer recurrence in oral cancer patients. Results: Fifty-two oral cancer patients and 52 healthy control cases were selected. In univariate analysis, salivary IL-6 and IL-8 seemed to be more expressed in cases (p<.001 and p=.010 respectively). Multivariate analysis showed that higher pretreatment saliva IL-6 levels were significantly associated with better survival (HR, 8.62; 95% CI, p=.031). Conclusions: To date, this is the largest prospective controlled study that analyses the pre-treatment salivary and serum levels of IL-6 and IL-8 in oral cancer patients, suggesting salivary IL-6 as possible prognostic biomarkers, but further validation on a larger sample is still necessary. Thank you for your decision and comments regarding the above manuscript.In order to expedite the processing of the revised manuscript, we have attempted to answer the reviewers' comment in a point-by-point manner.The attached highlights the changes in yellow.#Reviewer 1:-As required primary and secondary endpoints have been better described at the beginning of the M&M section.-Some lines about the sample size have been added, as required, when discussing about statistical methods.-As suggested, in the Discussion section the weaknesses and strengths of the study have been discussed; moreover, the potential clinical applications of the achieved results have been better commented.We now hope that our revisions will be acceptable. Conclusions: To date, this is the largest prospective controlled study that analyses the pre-treatment salivary and serum levels of IL-6 and IL-8 in oral cancer patients, suggesting salivary IL-6 as possible prognostic biomarkers, but further validation on a larger sample is still necessary.

Proinflammatory cytokines as serum biomarker in oral carcinoma—A prospective multi‐biomarker approach

“…There is clear evidence that proinflammatory growth factors play a vital role in cancer development and progression . However, clinical studies investigating serum levels of proinflammatory growth factors and cytokines are rare.…”

Salivary extracellular vesicle-associated miRNAs as potential biomarkers in oral squamous cell carcinoma

“…As previously reported [ 16 ], all subjects were asked to refrain from: eating, drinking, or oral hygiene for at least one hour prior to collection (usually between 9 and 11 a.m.); they then rinsed their mouths with water and then waited for at least 5 min before spitting into a 50 ml Falcon tube. Participants were instructed not to cough or forcefully expectorate in order to collect unstimulated saliva samples.…”

The Acute Phase Reaction and Its Prognostic Impact in Patients with Head and Neck Squamous Cell Carcinoma: Single Biomarkers Including C-Reactive Protein Versus Biomarker Profiles

“…Several previous studies have shown that both increased systemic CRP levels [ 8 , 47 , 48 , 49 , 50 , 51 , 52 ] and IL6 levels [ 9 , 21 , 22 , 23 , 53 , 54 , 55 , 56 , 57 ] are associated with an adverse prognosis in HNSCC. IL6 can function as a driver of the acute phase reaction, i.e., increased CRP levels can at least partly be due to an IL6 effect [ 1 , 26 ].…”

“…Inflammatory parameters are considered as possible prognostic markers in several human malignancies [ 9 , 55 ]. These parameters include both acute phase proteins and peripheral blood concentrations of various leukocyte subsets and platelets [ 62 , 72 , 73 , 74 , 75 ].…”

“…Systemic inflammatory responses, including the systemic levels of acute phase cytokines, have a prognostic impact in several cancers, including HNSCC [ 9 , 10 , 21 , 22 , 23 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ]. However, the acute phase reaction is an example of how several cytokines (including IL6 family and IL1 subfamily members as well as TNFα) form an interacting network [ 1 ].…”