Abstract
Introduction: Laryngeal squamous cell carcinoma (LSCC) is the most common type of laryngeal cancer, with around 60% of patients being diagnosed at an advanced stage. Recently, cancer-derived sialylated immunoglobulin G (SIA-IgG) has been suggested to play a role in the progression of various epithelial tumors, but its significance in LSCC remains unknown. This study aimed to investigate the clinical significance of SIA-IgG as a novel biomarker in relation to the initiation, progression, and prognostication of LSCC. Methods: Immunohistochemistry (IHC) was utilized to assess SIA-IgG expression in tumor samples from 75 LSCC patients, aiming to investigate its correlation with clinical prognosis. In vitro functional experiments were conducted to explore the impact of SIA-IgG expression on the proliferative and migratory abilities of laryngocarcinoma cells. Results: High expression of SIA-IgG was associated with pT stage, pN stage, TNM stage, and recurrence during follow-up and was correlated with poor disease-free survival (DFS) and overall survival (OS). Multivariate Cox analysis demonstrated that SIA-IgG served as an independent risk factor for OS and DFS. Knocking down SIA-IgG significantly weakened laryngocarcinoma cells’ proliferation, clonogenesis, and migration abilities. Conclusions: The frequent expression of SIA-IgG in LSCC is significantly associated with poor prognosis. High levels of SIA-IgG can enhance proliferation and migration in laryngocarcinoma cells. These findings suggest that SIA-IgG has potential as a novel biomarker for LSCC.
Journal Section:
Research Article
Plain Language Summary
While cancer-derived sialylated immunoglobulin G (SIA-IgG) has been found to promote the development of various epithelial tumors, research on its role in laryngeal cancer remains blank. Therefore, the objective of this study is to investigate the correlation between LSCC expression and clinical prognosis as well as the proliferation and migration abilities of laryngeal cancer cells.
Journal Section:
Research Article
References
1.
Sung
H
, Ferlay
J
, Siegel
RL
, Laversanne
M
, Soerjomataram
I
, Jemal
A
, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries
. CA Cancer J Clin
. 2021
;71
(3
):209
–49
. 2.
Siegel
RL
, Miller
KD
, Wagle
NS
, Jemal
A
. Cancer statistics, 2023
. CA Cancer J Clin
. 2023
;73
(1
):17
–48
. 3.
Marioni
G
, Marchese-Ragona
R
, Cartei
G
, Marchese
F
, Staffieri
A
. Current opinion in diagnosis and treatment of laryngeal carcinoma
. Cancer Treat Rev
. 2006
;32
(7
):504
–15
. 4.
Terro
W
, Crean
SJ
. Prospective, longitudinal assessment of quality of life in patients with cancer of the head and neck and their primary carers
. Br J Oral Maxillofac Surg
. 2017
;55
(6
):613
–7
. 5.
Kiem
D
, Wagner
S
, Magnes
T
, Egle
A
, Greil
R
, Melchardt
T
. The role of neutrophilic granulocytes in Philadelphia chromosome negative myeloproliferative neoplasms
. Int J Mol Sci
. 2021
;22
(17
):9555
. 6.
Solomon
B
, Young
RJ
, Rischin
D
. Head and neck squamous cell carcinoma: genomics and emerging biomarkers for immunomodulatory cancer treatments
. Semin Cancer Biol
. 2018
;52
(Pt 2
):228
–40
. 7.
Seiwert
TY
, Burtness
B
, Mehra
R
, Weiss
J
, Berger
R
, Eder
JP
, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial
. Lancet Oncol
. 2016
;17
(7
):956
–65
. 8.
Mehra
R
, Seiwert
TY
, Gupta
S
, Weiss
J
, Gluck
I
, Eder
JP
, et al. Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012
. Br J Cancer
. 2018
;119
(2
):153
–9
. 9.
Harrington
KJ
, Ferris
RL
, Blumenschein
G
Jr, Colevas
AD
, Fayette
J
, Licitra
L
, et al. Nivolumab versus standard, single-agent therapy of investigator’s choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trial
. Lancet Oncol
. 2017
;18
(8
):1104
–15
. 10.
Ferris
RL
, Blumenschein
G
Jr, Fayette
J
, Guigay
J
, Colevas
AD
, Licitra
L
, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck
. N Engl J Med
. 2016
;375
(19
):1856
–67
. 11.
Qiu
X
, Zhu
X
, Zhang
L
, Mao
Y
, Zhang
J
, Hao
P
, et al. Human epithelial cancers secrete immunoglobulin g with unidentified specificity to promote growth and survival of tumor cells
. Cancer Res
. 2003
;63
(19
):6488
–95
.12.
Liao
Q
, Liu
W
, Liu
Y
, Wang
F
, Wang
C
, Zhang
J
, et al. Aberrant high expression of immunoglobulin G in epithelial stem/progenitor-like cells contributes to tumor initiation and metastasis
. Oncotarget
. 2015
;6
(37
):40081
–94
. 13.
Babbage
G
, Ottensmeier
CH
, Blaydes
J
, Stevenson
FK
, Sahota
SS
. Immunoglobulin heavy chain locus events and expression of activation-induced cytidine deaminase in epithelial breast cancer cell lines
. Cancer Res
. 2006
;66
(8
):3996
–4000
. 14.
Zhang
L
, Hu
S
, Korteweg
C
, Chen
Z
, Qiu
Y
, Su
M
, et al. Expression of immunoglobulin G in esophageal squamous cell carcinomas and its association with tumor grade and Ki67
. Hum Pathol
. 2012
;43
(3
):423
–34
. 15.
Liang
PY
, Li
HY
, Zhou
ZY
, Jin
YX
, Wang
SX
, Peng
XH
, et al. Overexpression of immunoglobulin G prompts cell proliferation and inhibits cell apoptosis in human urothelial carcinoma
. Tumour Biol
. 2013
;34
(3
):1783
–91
. 16.
Tang
J
, Zhang
J
, Liu
Y
, Liao
Q
, Huang
J
, Geng
Z
, et al. Lung squamous cell carcinoma cells express non-canonically glycosylated IgG that activates integrin-FAK signaling
. Cancer Lett
. 2018
;430
:148
–59
. 17.
Lee
G
, Ge
B
. Cancer cell expressions of immunoglobulin heavy chains with unique carbohydrate-associated biomarker
. Cancer Biomark
. 2009
;5
(4
):177
–88
. 18.
Wang
Z
, Geng
Z
, Shao
W
, Liu
E
, Zhang
J
, Tang
J
, et al. Cancer-derived sialylated IgG promotes tumor immune escape by binding to Siglecs on effector T cells
. Cell Mol Immunol
. 2020
;17
(11
):1148
–62
. 19.
Wang
J
, Lin
D
, Peng
H
, Huang
Y
, Huang
J
, Gu
J
. Cancer-derived immunoglobulin G promotes tumor cell growth and proliferation through inducing production of reactive oxygen species
. Cell Death Dis
. 2013
;4
(12
):e945
. 20.
Wu
L
, Liu
Y
, Zhu
X
, Zhang
L
, Chen
J
, Zhang
H
, et al. The immunoglobulin heavy chain VH6-1 promoter regulates Ig transcription in non-B cells
. Cancer Cell Int
. 2014
;14
(1
):114
. 21.
Qin
C
, Sheng
Z
, Huang
X
, Tang
J
, Liu
Y
, Xu
T
, et al. Cancer-driven IgG promotes the development of prostate cancer though the SOX2-CIgG pathway
. Prostate
. 2020
;80
(13
):1134
–44
. 22.
Liu
Y
, Liu
D
, Wang
C
, Liao
Q
, Huang
J
, Jiang
D
, et al. Binding of the monoclonal antibody RP215 to immunoglobulin G in metastatic lung adenocarcinomas is correlated with poor prognosis
. Histopathology
. 2015
;67
(5
):645
–53
. 23.
Lee
G
, Chu
RA
, Ting
HH
. Preclinical assessment of anti-cancer drugs by using RP215 monoclonal antibody
. Cancer Biol Ther
. 2009
;8
(2
):161
–6
. 24.
Huang
X
, Zhang
S
, Tang
J
, Tian
T
, Pan
Y
, Wu
L
, et al. A self-propagating c-met-SOX2 Axis drives cancer-derived IgG signaling that promotes lung cancer cell stemness
. Cancer Res
. 2023
;83
(11
):1866
–82
. 25.
Ma
C
, Wang
Y
, Zhang
G
, Chen
Z
, Qiu
Y
, Li
J
, et al. Immunoglobulin G expression and its potential role in primary and metastatic breast cancers
. Curr Mol Med
. 2013
;13
(3
):429
–37
. 26.
Sheng
Z
, Liu
Y
, Qin
C
, Liu
Z
, Yuan
Y
, Hu
F
, et al. IgG is involved in the migration and invasion of clear cell renal cell carcinoma
. J Clin Pathol
. 2016
;69
(6
):497
–504
. 27.
Cui
M
, Hu
Y
, Zheng
B
, Zhang
S
, Zhang
X
, Wang
M
, et al. Cancer-derived immunoglobulin G: a novel marker for differential diagnosis and relapse prediction in parathyroid carcinoma
. Clin Endocrinol
. 2020
;92
(5
):461
–7
. 28.
Tang
Z
, Li
C
, Kang
B
, Gao
G
, Li
C
, Zhang
Z
. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses
. Nucleic Acids Res
. 2017
;45
(W1
):W98
–102
. 29.
Cui
M
, Huang
J
, Zhang
S
, Liu
Q
, Liao
Q
, Qiu
X
. Immunoglobulin expression in cancer cells and its critical roles in tumorigenesis
. Front Immunol
. 2021
;12
:613530
. 30.
Zhu
X
, Wu
L
, Zhang
L
, Hao
P
, Zhang
S
, Huang
J
, et al. Distinct regulatory mechanism of immunoglobulin gene transcription in epithelial cancer cells
. Cell Mol Immunol
. 2010
;7
(4
):279
–86
. 31.
Li
M
, Zheng
H
, Duan
Z
, Liu
H
, Hu
D
, Bode
A
, et al. Promotion of cell proliferation and inhibition of ADCC by cancerous immunoglobulin expressed in cancer cell lines
. Cell Mol Immunol
. 2012
;9
(1
):54
–61
. 32.
Duan
CG
, Liu
YF
, Li
KN
, Yu
L
, Cui
JH
, Li
J
, et al. Co-localization of the heat shock protein and human immunoglobulin G in hepatocellular carcinoma
. Chin Med J Engl
. 2005
;118
(23
):2011
–3
.33.
Niu
N
, Zhang
J
, Huang
T
, Sun
Y
, Chen
Z
, Yi
W
, et al. IgG expression in human colorectal cancer and its relationship to cancer cell behaviors
. PLoS One
. 2012
;7
(11
):e47362
. 34.
Liu
EY
, Liu
JF
, Shao
WW
, Xiao
L
, Li
GH
, Chang
XH
, et al. [Tumor derived IgG suppress the proliferation of T cells in cord blood]
. Beijing Da Xue Xue Bao Yi Xue Ban
. 2017
;49
(5
):824
–8
.35.
Lee
G
, Laflamme
E
, Chien
CH
, Ting
HH
. Molecular identity of a pan cancer marker, CA215
. Cancer Biol Ther
. 2008
;7
(12
):2007
–14
. 36.
Lee
G
, Ge
B
. Inhibition of in vitro tumor cell growth by RP215 monoclonal antibody and antibodies raised against its anti-idiotype antibodies
. Cancer Immunol Immunother
. 2010
;59
(9
):1347
–56
. 37.
Mannelli
G
, Cecconi
L
, Gallo
O
. Laryngeal preneoplastic lesions and cancer: challenging diagnosis. Qualitative literature review and meta-analysis
. Crit Rev Oncol Hematol
. 2016
;106
:64
–90
. 38.
Kolator
M
, Kolator
P
, Zatonski
T
. Assessment of quality of life in patients with laryngeal cancer: a review of articles
. Adv Clin Exp Med
. 2018
;27
(5
):711
–5
. 39.
Zhang
M
, Deng
W
, Gong
H
, Li
C
, Wang
Y
, Liu
X
, et al. Clinical effect of postoperative chemoradiotherapy in resected advanced laryngeal squamous cell carcinoma
. Oncol Lett
. 2019
;17
(5
):4717
–25
. 40.
Zhang
YF
, Shen
YJ
, Huang
Q
, Wu
CP
, Zhou
L
, Ren
HL
. Predicting survival of advanced laryngeal squamous cell carcinoma: comparison of machine learning models and Cox regression models
. Sci Rep
. 2023
;13
(1
):18498
. 41.
Wang
K
, Gui
L
, Lu
H
, He
X
, Li
D
, Liu
C
, et al. Efficacy and safety of pembrolizumab with preoperative neoadjuvant chemotherapy in patients with resectable locally advanced head and neck squamous cell carcinomas
. Front Immunol
. 2023
;14
:1189752
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