Role of serum cholinesterase and inflammatory markers in the prognosis of stage ⅠA -ⅢA breast cancer

doi:10.3760/cma.j.cn371439-20231008-00010

Abstract

Abstract:

Objective To analyze the preoperative and postoperative serum cholinesterase （CHE）levels in patients with stage ⅠA-ⅢA breast cancer who underwent surgical treatment， and to explore the roles of them and peripheral blood inflammatory markers in the prognostic prediction of stage ⅠA-ⅢA breast cancer. Methods The relevant blood indicators of 152 patients with stage ⅠA-ⅢA breast cancer who underwent surgery and postoperative adjuvant therapy from January 2012 to December 2017 at Affiliated Huai'an Hospital of Xuzhou Medical University were retrospectively studied. The optimal cut-off values of serum CHE levels and peripheral blood inflammatory markers [systemic immune-inflammation index （SII）and systemic inflammatory response index （SIRI）] were calculated using X-tile 3.6.1 software. Patients were categorized into low and high value groups based on the optimal cutoff values. Kaplan-Meier curves and Cox regression analysis were used to assess the correlation between CHE and peripheral blood inflammation indexes and disease-free survival （DFS）. Spearman correlation coefficient and Wilcoxon test were used to assess the correlation and changes of CHE and inflammation indexes before and after treatment. In addition to this， a nomogram prediction model was conscturcted based on independent prognostic factors by R software， which was validated by Bootstrap method. Results The CHE levels of patients before and after treatment was 8 645.0 （7 251.3， 10 229.3）and 9 309.0 （7 801.0， 10 835.3）U/L， respectively， with a statistically significant difference （Z=2.73， P=0.006）.The optimal cut-off values for postoperative CHE （Post-CHE）， postoperative SII （Post-SII）， and postoperative SIRI （Post-SIRI）associated with patients' DFS， being 7 773 U/L， 741， and 0.9， respectively. Univariate analysis showed that tumor size （≤2 cm vs.>2 cm and ≤5 cm：HR=2.55， 95%CI：1.30-4.99， P=0.006； ≤2 cm vs. >5 cm：HR=8.95， 95%CI：4.15-19.32， P<0.001）， number of positive lymph nodes （HR=3.84， 95%CI：2.24-6.58， P<0.001）， clinical stage （stage Ⅰ vs. stage Ⅱ：HR=1.52， 95%CI：0.68-3.39， P=0.309， stage Ⅰ vs. stage Ⅲ：HR=8.12， 95%CI：3.76-17.55， P<0.001）， Ki-67 expression （HR=2.19， 95%CI：1.24-3.84， P=0.007）， whether radiotherapy （HR=2.05， 95%CI：1.19-3.53， P=0.010）， Post-CHE （HR=6.81， 95%CI：3.94-11.76， P<0.001）， Pre-neutrophil to lymphocyte ratio （NLR）（HR=1.11， 95%CI：1.02-1.21， P=0.014）， Post-NLR （HR=5.23， 95%CI：2.78-9.85， P<0.001）， Pre-platelet to lymphocyte ratio （PLR）（HR=2.08， 95%CI：1.01-4.26， P=0.046）， Post-PLR （HR=7.11， 95%CI：3.78-13.37， P<0.001）， Pre-lymphocyte to monocyte ratio （LMR）（HR=0.37， 95%CI：0.20-0.66， P<0.001）， Post-LMR （HR=0.23， 95%CI：0.13-0.41， P<0.001）， Pre-SII （HR=1.81， 95%CI：1.05-3.12， P=0.033）， Post-SII （HR=6.12， 95%CI：3.48-10.76， P<0.001）， Pre-SIRI （HR=2.12， 95%CI：1.24-3.63， P=0.006）， and Post-SIRI （HR=4.93， 95%CI：2.87-8.48， P<0.001）were associated with DFS in patients with stage ⅠA-ⅢA breast cancer. Multivariate analysis showed that tumor size （≤2 cm vs. >2 cm and ≤5 cm：HR=2.86， 95%CI：1.41-5.78， P=0.003； ≤2 cm vs. >5 cm：HR=3.72， 95%CI：1.50-9.26， P=0.005）， number of positive lymph nodes （HR=4.66， 95%CI：2.28-9.54， P<0.001）， Ki-67 expression （HR=2.13， 95%CI：1.15-3.94， P=0.016）， Post-CHE （HR=0.18， 95%CI：0.10-0.33， P<0.001）， Post-SII （HR=2.71， 95%CI：1.39-5.29， P=0.004）， and Post-SIRI （HR=3.77， 95%CI：1.93-7.36， P<0.001）were independent influencing factors for DFS in patients with stage ⅠA-ⅢA breast cancer. Kaplan-Meier survival curve analysis showed that the median DFS of patients in the Ki-67<30% group was not reached， and the median DFS of patients in the Ki-67≥30% group was 89.0 months， and the 3- and 5-year DFS rates were 84.9% vs. 75.9% and 80.8% vs. 64.3%， respectively， with a statistically significant difference （χ²=7.65， P=0.006）； the median DFS of patients in the tumor size≤2 cm group was not reached， the median DFS of the 2 cm<tumor size≤5 cm group was 93.5 months， and the median DFS of the tumor size>5 cm group was 26.3 months， and the 3- and 5-year DFS rates were 95.5% vs. 74.6% vs. 42.1%， 86.3% vs. 68.6% vs. 25.3%， with a statistically significant difference （χ²=40.46， P<0.001）； the median DFS of patients in the group with the number of positive lymph nodes<4 was not reached， and the median DFS of the group with the number of positive lymph nodes≥4 was 30.7 months， and the 3- and 5-year DFS rates were 87.9% vs. 46.4% and 81.4% vs. 28.6%， respectively， with a statistically significant difference （χ²= 47.34， P<0.001）； the median DFS of patients in the Post-CHE<7 773 U/L group was 47.3 months， and the median DFS of patients in the Post-CHE≥7 773 U/L group was not reached， and the 3- and 5-year DFS rates were 52.8 % vs. 88.6% and 27.8% vs. 81.2%， respectively， with a statistically significant difference （χ²=62.17， P<0.001）； the median DFS was not achieved in patients in the Post-SII<741 group， and the median DFS was 30.5 months in the Post-SII≥741 group， with 3- and 5-year DFS rates of 88.1% vs. 38.5% and 80.1% vs. 30.8%， respectively， with a statistically significant difference （χ²=50.78， P<0.001）； the median DFS of patients in Post-SIRI<0.9 group was not reached， the median DFS of Post-SIRI≥0.9 group was 33.3 months， and the 3- and 5-year DFS rates were 93.5% vs. 46.7% and 84.9% vs. 39.9%， respectively， with a statistically significant difference （χ²=40.67， P<0.001）. Spearman correlation analysis revealed that Post-CHE was not correlated with Post-SII （r=-0.111， P=0.175）， and Post-CHE was negatively correlated with Post-SIRI （r=-0.228， P=0.005）. Post-treatment CHE was elevated compared to preoperative and the median DFS was not reached in patients with elevated CHE group and 61.8 months in patients with reduced CHE group after treatment， with a statistically significant difference （χ²=25.67， P<0.001）. The nomogram based on independent prognostic factors had good predictive performance， with a C-index of 0.893. Conclusion The serum CHE level exhibited a significant increase following treatment. Postoperative serum CHE combined with SII and SIRI can effectively predict DFS in patients with stage ⅠA-ⅢA breast cancer， and the prognosis of patients with elevated CHE after treatment is better. The nomogram constructed based on independent prognostic factors has good predictive performance for DFS in breast cancer patients.

Key words: Breast neoplasms, Cholinesterase, Systemic immune-inflammatory index, Systemic inflammatory response index, Prognosis, Nomogram

Chen Boguang, Wang Sugui, Zhang Yongjie. Role of serum cholinesterase and inflammatory markers in the prognosis of stage ⅠA -ⅢA breast cancer[J]. Journal of International Oncology, 2024, 51(2): 73-82.

Figures/Tables 7

项目	例数（%）	单因素分析			多因素分析
项目	例数（%）	HR值	95%CI	P值	HR值	95%CI	P值
年龄（岁）
<50	70（46.1）	1
≥50	82（53.9）	0.65	0.38~1.12	0.118
手术方式
保乳	13（8.6）	1
改良根治术	139（91.4）	0.98	0.39~2.45	0.960
肿瘤大小（cm）
≤2	66（43.4）	1			1
>2且≤5	67（44.1）	2.55	1.30~4.99	0.006	2.86	1.41~5.78	0.003
>5	19（12.5）	8.95	4.15~19.32	<0.001	3.72	1.50~9.26	0.005
阳性淋巴结数目（个）
<4	28（18.4）	1			1
≥4	124（81.6）	3.84	2.24~6.58	<0.001	4.66	2.28~9.54	<0.001
临床分期
Ⅰ	46（30.3）	1			1
Ⅱ	72（47.3）	1.52	0.68~3.39	0.309	0.52	0.14~1.92	0.325
Ⅲ	34（22.4）	8.12	3.76~17.55	<0.001	1.27	0.24~6.79	0.777
免疫分型
Luminal A	55（36.2）	1
Luminal B	15（9.9）	1.71	0.71~4.13	0.233
三阴性	19（12.5）	1.44	0.60~3.47	0.420
人表皮生长因子受体2过表达	63（41.4）	1.32	0.71~2.48	0.381
Ki-67表达
<30%	73（48.0）	1			1
≥30%	79（52.0）	2.19	1.24~3.84	0.007	2.13	1.15~3.94	0.016
病理类型
浸润性导管癌	132（86.8）	1
其他	20（13.2）	0.63	0.25~1.57	0.319
是否放疗
是	109（71.7）	1			1
否	43（28.3）	2.05	1.19~3.53	0.010	1.01	0.45~2.26	0.976
Pre-CHE（U/L）
<6 975	124（81.6）	1
≥6 975	28（18.4）	1.80	0.97~3.31	0.061
Post-CHE（U/L）
<7 773	116（76.3）	1			1
≥7 773	36（23.7）	6.81	3.94~11.76	<0.001	0.18	0.10~0.33	<0.001
Pre-NLR
<1.5	34（22.4）	1			1
≥1.5	118（77.6）	1.11	1.02~1.21	0.014	1.25	0.41~3.85	0.696
Post-NLR
<3.8	136（89.5）	1			1
≥3.8	16（10.5）	5.23	2.78~9.85	<0.001	0.69	0.29~1.61	0.390
Pre-PLR
<207.0	136（89.5）	1			1
≥207.0	16（10.5）	2.08	1.01~4.26	0.046	1.21	0.44~3.36	0.717
Post-PLR
<270.8	136（89.5）	1			1
≥270.8	16（10.5）	7.11	3.78~13.37	<0.001	1.25	0.45~3.42	0.671
Pre-LMR
<6.3	83（54.6）	1			1
≥6.3	69（45.4）	0.37	0.20~0.66	<0.001	0.53	0.23~1.21	0.129
Post-LMR
<3.1	22（14.5）	1			1
≥3.1	130（85.5）	0.23	0.13~0.41	<0.001	0.75	0.34~1.65	0.471
Pre-SII
<479	79（52.0）	1			1
≥479	73（48.0）	1.81	1.05~3.12	0.033	1.47	0.49~4.48	0.494
Post-SII
<741	126（82.9）	1			1
≥741	26（17.1）	6.12	3.48~10.76	<0.001	2.71	1.39~5.29	0.004
Pre-SIRI
<0.7	95（62.5）	1			1
≥0.7	57（37.5）	2.12	1.24~3.63	0.006	0.72	0.35~1.45	0.353
Post-SIRI
<0.9	107（70.4）	1			1
≥0.9	45（29.6）	4.93	2.87~8.48	<0.001	3.77	1.93~7.36	<0.001
注：DFS为无瘤生存期；Pre-为术前；Post-为术后；CHE为胆碱酯酶；NLR为中性粒细胞/淋巴细胞比值；PLR为血小板/淋巴细胞比值；LMR为淋巴细胞/单核细胞比值；SII为全身免疫炎症指数；SIRI为全身炎症反应指数

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