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©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
Tumor-infiltrating platelets predict postoperative recurrence and survival in resectable pancreatic neuroendocrine tumor
Shuai-Shuai Xu, Hua-Xiang Xu, Wen-Quan Wang, Shuo Li, Hao Li, Tian-Jiao Li, Wu-Hu Zhang, Liang Liu, Xian-Jun Yu
Shuai-Shuai Xu, Hua-Xiang Xu, Wen-Quan Wang, Shuo Li, Hao Li, Tian-Jiao Li, Wu-Hu Zhang, Liang Liu, Xian-Jun Yu, Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 20032, China
Shuai-Shuai Xu, Hua-Xiang Xu, Wen-Quan Wang, Shuo Li, Hao Li, Tian-Jiao Li, Wu-Hu Zhang, Liang Liu, Xian-Jun Yu, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Shuai-Shuai Xu, Hua-Xiang Xu, Wen-Quan Wang, Shuo Li, Hao Li, Tian-Jiao Li, Wu-Hu Zhang, Liang Liu, Xian-Jun Yu, Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
Shuai-Shuai Xu, Hua-Xiang Xu, Wen-Quan Wang, Shuo Li, Hao Li, Tian-Jiao Li, Wu-Hu Zhang, Liang Liu, Xian-Jun Yu, Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
Author contributions: Xu SS, Wang WQ, and Li S contributed equally to this work, in conducting clinical observations, analyzing the data, and writing the manuscript; Xu SS, Xu HX, Wang WQ, Li S, Li H, Li TJ, and Zhang WH performed the research; Xu HX, Liu L, and Yu XJ contributed equally to this work, in designing the research, revising the manuscript, and providing valuable suggestions for this study.
Supported by grants from the National Science Foundation for Distinguished Young Scholars of China, No. 81625016; the National Natural Science Foundation of China, No. 81871941, No. 81872366, No. 81827807, No. 81802675, and No. 81702341; the Outstanding Academic Leader Program of the “ Technological Innovation Action Plan” in Shanghai Science and Technology Commission, No. 18XD1401200; and the Young Talented Specialist Training Program of Shanghai.
Institutional review board statement: This study was reviewed and approved by the Human Research Ethics Committee of Fudan University Shanghai Cancer Center.
Informed consent statement: Written informed consent has been acquired from each patient.
Conflict-of-interest statement: All authors declare no conflicts of interest related to this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Liang Liu, MD, PhD, Professor, Surgeon, Surgical Oncologist, Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai 200032, China. liuliang@fudanpci.org
Telephone: +86-21-64031446 Fax: +86-21-64031446
Received: May 22, 2019
Peer-review started: May 22, 2019
First decision: June 16, 2019
Revised: July 8, 2019
Accepted: July 19, 2019
Article in press: June 16, 2019
Published online: November 7, 2019
ARTICLE HIGHLIGHTS
Research background
Pancreatic neuroendocrine tumor (pNET) is the second most common malignancy among pancreatic tumors. Most studies have primarily concentrated on the significance of tumor cells, but few have focused on the importance of the tumor microenvironment in pNET. Platelets are an important component of the tumor microenvironment. However, the importance of platelets in pNET lacks adequate literature support.
Research motivation
To assess the potential clinical meaning of platelets in pNET and offer evidence concerning a potential anti-platelet therapeutic strategy for pNET.
Research objectives
Tumor-infiltrating platelets are potential independent indicators of survival and recurrence outcome for patients with resectable pNET.
Research methods
In total, 113 patients who had undergone radical surgical resection were retrospectively enrolled. All the specimens were selected via pathologic diagnosis of pNET without distant metastasis or other tumor history. None of the patients had received any preoperative chemotherapy or radiotherapy or died of postoperative complications within 30 d. Immunohistochemical analysis of CD42b expression in tumor specimens was performed to determine the presence of TIPs. Univariate and multivariate analyses were applied to analyze the prognostic value of tumor-infiltrating platelets.
Research results
Tumor-infiltrating platelets were observed in intratumoral areas in 54 patients. Neither basic characteristics nor preoperative platelet count, mean platelet volume, or platelet lymphoid ratio showed a statistical relationship with CD42b expression. Platelet count, mean platelet volume, and platelet-to-lymphocyte ratio determined by preoperative blood tests were not related to overall survival or recurrence-free survival. Tumor-infiltrating platelets were found to be potential independent indicators of survival and recurrence outcome for patients with resectable pNET. The major limitations were that the nature of a retrospective study with a limited sample size restricts the level of evidence and that the mechanism by which platelets influence the recurrence of patients was not thoroughly investigated.
Research conclusions
We uncovered a relationship between tumor-infiltrating platelets and the prognosis of patients with pNET following radical resection. We found that tumor-infiltrating platelets were potential pNET prognosis indicators. In addition, therapy targeting platelets in pNET could improve long-term survival. We further provide the clinical meaning of platelets in the tumor microenvironment in pNET.
Research perspectives
A further prospective study with a large sample size should be conducted with multicenter cooperation, and additional experiments to assess the mechanism need to be implemented. If possible, we recommend a randomized double-blind controlled clinical trial for platelet-targeted therapy for pNET.
