We appreciate to receive commentary from Dr Guangtong Deng and Dr Liang Xiao to our article, “Nomograms based on inflammatory biomarkers for predicting tumor grade and micro-vascular invasion in stage I/II hepatocellular carcinoma”. First, neutrophil-to-lymphocyte ratio (NLR) and derived NLR (dNLR) are two different parameters. Some studies show that NLR is inconsistent with dNRL in prognostic value through multivariate Cox regression, therefore, it is reasonable that both NLR and dNLR entered into multivariate analysis simultaneously. Second, it is common that articles of predictive nomograms turned continuous variables into categorical variables. The reason is that the categorization of patient clinical variables is beneficial to doctors to make decisions based on the risk level of individual patients in clinical. At last, multicenter validation is quite difficult and we have listed the shortcomings in the limitations of our article. Further validation will need the joint efforts by other institutions.

We thank Dr Guangtong Deng and Dr Liang Xiao for their valuable comments and suggestions on “Nomograms based on inflammatory biomarkers for predicting tumor grade and micro-vascular invasion in stage I/II hepatocellular carcinoma [1]”.

First, neutrophil-to-lymphocyte ratio (NLR) is equal to neutrophil divided by lymphocyte. However, derived neutrophil-to-lymphocyte ratio (dNLR) is that neutrophil count divided by the result of white cell count minus neutrophil count [2]. NLR and dNLR are two different parameters. Furthermore, some studies show that NLR is inconsistent with dNRL in prognostic value through multivariate Cox regression [2–8]. Therefore, it is reasonable that both NLR and dNLR entered into multivariate analysis simultaneously.

Second, 86% of epidemiological investigations classified continuity factors to categorical variables [9]. The advantages of categorization are listed as follows: (1) The results may be more readily understood by non-statisticians. (2) Categorization may remove the need for any parametric assumptions regarding the shape [9]. In clinical, categorization is easily obtained and the categorization of patient clinical variables is conducive for doctors to make decisions based on the risk level of individual patients [10]. In addition, many excellent articles of predictive nomograms also turned continuous variables into categorical variables [11,12]. We have mentioned the setting of the cut-off values in the method of our article – ‘Receiver operating characteristic (ROC) curve analysis was used to calculate the optimal cutoff values that were determined by maximizing the Youden index (i.e., sensitivity+specificity-1). Accuracy of the optimal cutoff value was assessed by the sensitivity, specificity, predictive values, and likelihood ratios’.

Last, the purpose of our article is to develop nomograms predicting tumor grade and MVI based on inflammatory biomarkers with high accuracy. Due to experimental resource limitations, the step of an independent dataset validation is not included. As most published articles, we have listed the shortcomings, lacking of validation by other research institutes, in the limitations of our article.

The authors declare that there are no competing interests associated withthe manuscript.

dNLR

derived neutrophil-to-lymphocyte ratio

MVI

micro-vascular invision

NLR

neutrophil-to-lymphocyte ratio

ROC

receiver operating characteristic

1.
Li
P.
,
Huang
W.
,
Wang
F.
,
Ke
Y.F.
,
Gao
L.
,
Shi
K.Q.
et al.
(
2018
)
Nomograms based on inflammatory biomarkers for predicting tumor grade and micro-vascular invasion in stage I/II hepatocellular carcinoma
.
Biosci. Rep.
38
,
2.
Capone
M.
,
Giannarelli
D.
,
Mallardo
D.
,
Madonna
G.
,
Festino
L.
,
Grimaldi
A.M.
et al.
(
2018
)
Baseline neutrophil-to-lymphocyte ratio (NLR) and derived NLR could predict overall survival in patients with advanced melanoma treated with nivolumab
.
J. Immunother. Cancer
6
,
74
3.
Jin
H.
,
Sun
J.
,
Zhu
K.
,
Liu
X.
,
Zhang
Q.
,
Shen
Q.
et al.
(
2017
)
The prognostic value of neutrophil-lymphocyte ratio is superior to derived neutrophil-lymphocyte ratio in advanced gastric cancer treated with preoperative chemotherapy and sequential R0 resection: a 5-year follow-up
.
Onco Targets Ther.
10
,
2655
2664
[PubMed]
4.
Yuk
H.D.
,
Jeong
C.W.
,
Kwak
C.
,
Kim
H.H.
and
Ku
J.H.
(
2018
)
Elevated neutrophil to lymphocyte ratio predicts poor prognosis in non-muscle invasive bladder cancer patients: initial intravesical Bacillus Calmette-Guerin treatment after transurethral resection of bladder tumor setting
.
Front. Oncol.
8
,
642
[PubMed]
5.
Gu
L.
,
Ma
X.
,
Li
H.
,
Chen
L.
,
Xie
Y.
,
Zhao
C.
et al.
(
2016
)
Prognostic value of preoperative inflammatory response biomarkers in patients with sarcomatoid renal cell carcinoma and the establishment of a nomogram
.
Sci. Rep.
6
,
23846
[PubMed]
6.
Ying
H.Q.
,
Deng
Q.W.
,
He
B.S.
,
Pan
Y.Q.
,
Wang
F.
,
Sun
H.L.
et al.
(
2014
)
The prognostic value of preoperative NLR, d-NLR, PLR and LMR for predicting clinical outcome in surgical colorectal cancer patients
.
Med. Oncol.
31
,
305
[PubMed]
7.
Song
S.
,
Li
C.
,
Li
S.
,
Gao
H.
,
Lan
X.
and
Xue
Y.
(
2017
)
Derived neutrophil to lymphocyte ratio and monocyte to lymphocyte ratio may be better biomarkers for predicting overall survival of patients with advanced gastric cancer
.
Onco Targets Ther.
10
,
3145
3154
[PubMed]
8.
Deng
Q.
,
He
B.
,
Liu
X.
,
Yue
J.
,
Ying
H.
,
Pan
Y.
et al.
(
2015
)
Prognostic value of pre-operative inflammatory response biomarkers in gastric cancer patients and the construction of a predictive model
.
J. Transl. Med.
13
,
66
[PubMed]
9.
Turner
E.L.
,
Dobson
J.E.
and
Pocock
S.J.
(
2010
)
Categorisation of continuous risk factors in epidemiological publications: a survey of current practice
.
Epidemiol. Perspect. Innov.
7
,
9
10.
Barrio
I.
,
Arostegui
I.
,
Rodriguez-Alvarez
M.X.
and
Quintana
J.M.
(
2017
)
A new approach to categorising continuous variables in prediction models: proposal and validation
.
Stat. Methods Med. Res.
26
,
2586
2602
[PubMed]
11.
Fakhry
C.
,
Zhang
Q.
,
Nguyen-Tan
P.F.
,
Rosenthal
D.I.
,
Weber
R.S.
,
Lambert
L.
et al.
(
2017
)
Development and validation of nomograms predictive of overall and progression-free survival in patients with oropharyngeal cancer
.
J. Clin. Oncol.
35
,
4057
4065
12.
Tang
X.R.
,
Li
Y.Q.
,
Liang
S.B.
,
Jiang
W.
,
Liu
F.
,
Ge
W.X.
et al.
(
2018
)
Development and validation of a gene expression-based signature to predict distant metastasis in locoregionally advanced nasopharyngeal carcinoma: a retrospective, multicentre, cohort study
.
Lancet Oncol.
19
,
382
393
[PubMed]
This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).