Cytoplasmic expression of C-MYC protein is associated with risk stratification of mantle cell lymphoma

Aim To investigate the association of C-MYC protein expression and risk stratification in mantle cell lymphoma (MCL), and to evaluate the utility of C-MYC protein as a prognostic biomarker in clinical practice. Methods We conducted immunohistochemical staining of C-MYC, Programmed cell death ligand...

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Main Authors: Yi Gong, Xi Zhang, Rui Chen, Yan Wei, Zhongmin Zou, Xinghua Chen
Format: Article
Language:English
Published: PeerJ Inc. 2017-06-01
Series:PeerJ
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Online Access:https://peerj.com/articles/3457.pdf
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author Yi Gong
Xi Zhang
Rui Chen
Yan Wei
Zhongmin Zou
Xinghua Chen
author_facet Yi Gong
Xi Zhang
Rui Chen
Yan Wei
Zhongmin Zou
Xinghua Chen
author_sort Yi Gong
collection DOAJ
description Aim To investigate the association of C-MYC protein expression and risk stratification in mantle cell lymphoma (MCL), and to evaluate the utility of C-MYC protein as a prognostic biomarker in clinical practice. Methods We conducted immunohistochemical staining of C-MYC, Programmed cell death ligand 1 (PD-L1), CD8, Ki-67, p53 and SRY (sex determining region Y) -11 (SOX11) to investigate their expression in 64 patients with MCL. The staining results and other clinical data were evaluated for their roles in risk stratification of MCL cases using ANOVA, Chi-square, and Spearman’s Rank correlation coefficient analysis. Results Immunohistochemical staining in our study indicated that SOX11, Ki-67 and p53 presented nuclear positivity of tumor cells, CD8 showed membrane positivity in infiltrating T lymphocytes while PD-L1 showed membrane and cytoplasmic positivity mainly in macrophage cells and little in tumor cells. We observed positive staining of C-MYC either in the nucleus or cytoplasm or in both subcellular locations. There were significant differences in cytoplasmic C-MYC expression, Ki-67 proliferative index of tumor cells, and CD8 positive tumor infiltrating lymphocytes (CD8+TIL) among three risk groups (P = 0.000, P = 0.037 and P=0.020, respectively). However, no significant differences existed in the expression of nuclear C-MYC, SOX11, p53, and PD-L1 in MCL patients with low-, intermediate-, and high risks. In addition, patient age and serum LDH level were also significantly different among 3 groups of patients (P = 0.006 and P = 0.000, respectively). Spearman’s rank correlation coefficient analysis indicated that cytoplasmic C-MYC expression, Ki-67 index, age, WBC, as well as LDH level had significantly positive correlations with risk stratification (P = 0.000, 0.015, 0.000, 0.029 and 0.000, respectively), while CD8+TIL in tumor microenvironment negatively correlated with risk stratification of patients (P = 0.006). Patients with increased positive cytoplasmic expression of C-MYC protein and decreased CD8+TIL appeared to be associated with a poor response to chemotherapy, but the correlation was not statistically significant. Conclusion Our study suggested that assessment of cytoplasmic C-MYC overexpression and cytotoxic T lymphocytes (CTLs) by immunohistochemical staining might be helpful for MCL risk stratification and outcome prediction. However, large cohort studies of MCL patients with complete follow up are needed to validate our speculation.
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spelling doaj.art-1cc329216bd94dfd95416ed72c21ca0b2023-12-03T11:28:39ZengPeerJ Inc.PeerJ2167-83592017-06-015e345710.7717/peerj.3457Cytoplasmic expression of C-MYC protein is associated with risk stratification of mantle cell lymphomaYi Gong0Xi Zhang1Rui Chen2Yan Wei3Zhongmin Zou4Xinghua Chen5Department of Hematology, Xinqiao Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Hematology, Xinqiao Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Pathology, Chongqing Cancer Institute/Hospital, Chongqing, ChinaDepartment of Pathology, Xinqiao Hospital, The Third Military Medical University, Chongqing, ChinaInstitute of Toxicology, School of Preventive Medicine, The Third Military Medical University, Chongqing, ChinaDepartment of Hematology, Xinqiao Hospital, The Third Military Medical University, Chongqing, ChinaAim To investigate the association of C-MYC protein expression and risk stratification in mantle cell lymphoma (MCL), and to evaluate the utility of C-MYC protein as a prognostic biomarker in clinical practice. Methods We conducted immunohistochemical staining of C-MYC, Programmed cell death ligand 1 (PD-L1), CD8, Ki-67, p53 and SRY (sex determining region Y) -11 (SOX11) to investigate their expression in 64 patients with MCL. The staining results and other clinical data were evaluated for their roles in risk stratification of MCL cases using ANOVA, Chi-square, and Spearman’s Rank correlation coefficient analysis. Results Immunohistochemical staining in our study indicated that SOX11, Ki-67 and p53 presented nuclear positivity of tumor cells, CD8 showed membrane positivity in infiltrating T lymphocytes while PD-L1 showed membrane and cytoplasmic positivity mainly in macrophage cells and little in tumor cells. We observed positive staining of C-MYC either in the nucleus or cytoplasm or in both subcellular locations. There were significant differences in cytoplasmic C-MYC expression, Ki-67 proliferative index of tumor cells, and CD8 positive tumor infiltrating lymphocytes (CD8+TIL) among three risk groups (P = 0.000, P = 0.037 and P=0.020, respectively). However, no significant differences existed in the expression of nuclear C-MYC, SOX11, p53, and PD-L1 in MCL patients with low-, intermediate-, and high risks. In addition, patient age and serum LDH level were also significantly different among 3 groups of patients (P = 0.006 and P = 0.000, respectively). Spearman’s rank correlation coefficient analysis indicated that cytoplasmic C-MYC expression, Ki-67 index, age, WBC, as well as LDH level had significantly positive correlations with risk stratification (P = 0.000, 0.015, 0.000, 0.029 and 0.000, respectively), while CD8+TIL in tumor microenvironment negatively correlated with risk stratification of patients (P = 0.006). Patients with increased positive cytoplasmic expression of C-MYC protein and decreased CD8+TIL appeared to be associated with a poor response to chemotherapy, but the correlation was not statistically significant. Conclusion Our study suggested that assessment of cytoplasmic C-MYC overexpression and cytotoxic T lymphocytes (CTLs) by immunohistochemical staining might be helpful for MCL risk stratification and outcome prediction. However, large cohort studies of MCL patients with complete follow up are needed to validate our speculation.https://peerj.com/articles/3457.pdfMantle cell lymphomaMIPICytoplasmic C-MYCKi-67CD8+TILRisk stratification
spellingShingle Yi Gong
Xi Zhang
Rui Chen
Yan Wei
Zhongmin Zou
Xinghua Chen
Cytoplasmic expression of C-MYC protein is associated with risk stratification of mantle cell lymphoma
PeerJ
Mantle cell lymphoma
MIPI
Cytoplasmic C-MYC
Ki-67
CD8+TIL
Risk stratification
title Cytoplasmic expression of C-MYC protein is associated with risk stratification of mantle cell lymphoma
title_full Cytoplasmic expression of C-MYC protein is associated with risk stratification of mantle cell lymphoma
title_fullStr Cytoplasmic expression of C-MYC protein is associated with risk stratification of mantle cell lymphoma
title_full_unstemmed Cytoplasmic expression of C-MYC protein is associated with risk stratification of mantle cell lymphoma
title_short Cytoplasmic expression of C-MYC protein is associated with risk stratification of mantle cell lymphoma
title_sort cytoplasmic expression of c myc protein is associated with risk stratification of mantle cell lymphoma
topic Mantle cell lymphoma
MIPI
Cytoplasmic C-MYC
Ki-67
CD8+TIL
Risk stratification
url https://peerj.com/articles/3457.pdf
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