Nomogram to Predict Tumor-Infiltrating Lymphocytes in Breast Cancer Patients

Background: Tumor-infiltrating lymphocytes (TILs) play important roles in the prediction of prognosis and neoadjuvant therapy (NAT) efficacy in breast cancer (BRCA) patients, in this study, we identified clinicopathological factors related to BRCA TILs, then to construct and validate nomogram to pre...

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Autores principales:	Jikun Feng, Jianxia Li, Xinjian Huang, Jiarong Yi, Haoming Wu, Xuxiazi Zou, Wenjing Zhong, Xi Wang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	breast cancer tumor-infiltrating lymphocytes (TILs) nomogram neoadjuvant therapy (NAC) precise medicine Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/cfb8afe998404d68baab4fc96458d811
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spelling	oai:doaj.org-article:cfb8afe998404d68baab4fc96458d8112021-12-01T08:30:20ZNomogram to Predict Tumor-Infiltrating Lymphocytes in Breast Cancer Patients2296-889X10.3389/fmolb.2021.761163https://doaj.org/article/cfb8afe998404d68baab4fc96458d8112021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.761163/fullhttps://doaj.org/toc/2296-889XBackground: Tumor-infiltrating lymphocytes (TILs) play important roles in the prediction of prognosis and neoadjuvant therapy (NAT) efficacy in breast cancer (BRCA) patients, in this study, we identified clinicopathological factors related to BRCA TILs, then to construct and validate nomogram to predict high density of TILs.Methods: A total of 826 patients diagnosed with BRCA in Sun Yat-Sen University cancer center were enrolled in nomogram cohort. TILs were assessed using hematoxylin-eosin (H&E) staining by two pathologists. Complete clinical data were collected for analysis. Then the enrolled patients were split into a training set and validation set at a ratio of 8:2. and the backward multivariate binary logistic regression model was used to establish nomogram for predicting BRCA TILs, which were further evaluated and validated using the C-index, receiver operating characteristic (ROC) curves and calibration curves. Then another independent NAT cohort of 106 patients was established for verifying this nomogram in NAT efficacy prediction.Results: TILs were significantly correlated with body mass index (BMI), tumor differentiation, ER, PR, HER2 expression, Ki67, blood biochemical indicators including total bilirubin (TBIL), indirect bilirubin (IBIL), total protein (TP), Globulin (GLOB), inorganic phosphorus (IP), calcium (Ca). In which ER expression level [OR = 0.987, 95%CI (0.982–0.992), p < 0.001], IP [OR = 4.462, 95%CI (1.171∼17.289), p = 0.029], IBIL [OR = 0.906, 95%CI (0.845–0.966), p = 0.004] and TP [OR = 1.053, 95%CI (1.010–1.098, p = 0.016)] were independent predictors of TILs. Then nomogram was established, for which calibration curves (C-index = 0.759) and ROC curve (AUC = 0.759, 95%CI 0.717–0.801) in training sets, calibration curves (C-index = 0.708) and ROC curve (AUC = 0.708, 95%CI 0.617–0.800) in validation sets demonstrated great evaluation efficiency. Besides, independent NAT cohort verified this nomogram can distinguish patients with greater NAT efficacy (p = 0.041).Conclusion: The finds of clinicopathological factors associated with TILs could help clinicians to understand the tumor immunity of BRCA and improve treatment system for patients, and the established nomogram with high evaluation efficiency may be used as a complement tool for distinguishing patients with better NAT efficacy.Jikun FengJianxia LiXinjian HuangJiarong YiHaoming WuXuxiazi ZouWenjing ZhongXi WangFrontiers Media S.A.articlebreast cancertumor-infiltrating lymphocytes (TILs)nomogramneoadjuvant therapy (NAC)precise medicineBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	breast cancer tumor-infiltrating lymphocytes (TILs) nomogram neoadjuvant therapy (NAC) precise medicine Biology (General) QH301-705.5
spellingShingle	breast cancer tumor-infiltrating lymphocytes (TILs) nomogram neoadjuvant therapy (NAC) precise medicine Biology (General) QH301-705.5 Jikun Feng Jianxia Li Xinjian Huang Jiarong Yi Haoming Wu Xuxiazi Zou Wenjing Zhong Xi Wang Nomogram to Predict Tumor-Infiltrating Lymphocytes in Breast Cancer Patients
description	Background: Tumor-infiltrating lymphocytes (TILs) play important roles in the prediction of prognosis and neoadjuvant therapy (NAT) efficacy in breast cancer (BRCA) patients, in this study, we identified clinicopathological factors related to BRCA TILs, then to construct and validate nomogram to predict high density of TILs.Methods: A total of 826 patients diagnosed with BRCA in Sun Yat-Sen University cancer center were enrolled in nomogram cohort. TILs were assessed using hematoxylin-eosin (H&E) staining by two pathologists. Complete clinical data were collected for analysis. Then the enrolled patients were split into a training set and validation set at a ratio of 8:2. and the backward multivariate binary logistic regression model was used to establish nomogram for predicting BRCA TILs, which were further evaluated and validated using the C-index, receiver operating characteristic (ROC) curves and calibration curves. Then another independent NAT cohort of 106 patients was established for verifying this nomogram in NAT efficacy prediction.Results: TILs were significantly correlated with body mass index (BMI), tumor differentiation, ER, PR, HER2 expression, Ki67, blood biochemical indicators including total bilirubin (TBIL), indirect bilirubin (IBIL), total protein (TP), Globulin (GLOB), inorganic phosphorus (IP), calcium (Ca). In which ER expression level [OR = 0.987, 95%CI (0.982–0.992), p < 0.001], IP [OR = 4.462, 95%CI (1.171∼17.289), p = 0.029], IBIL [OR = 0.906, 95%CI (0.845–0.966), p = 0.004] and TP [OR = 1.053, 95%CI (1.010–1.098, p = 0.016)] were independent predictors of TILs. Then nomogram was established, for which calibration curves (C-index = 0.759) and ROC curve (AUC = 0.759, 95%CI 0.717–0.801) in training sets, calibration curves (C-index = 0.708) and ROC curve (AUC = 0.708, 95%CI 0.617–0.800) in validation sets demonstrated great evaluation efficiency. Besides, independent NAT cohort verified this nomogram can distinguish patients with greater NAT efficacy (p = 0.041).Conclusion: The finds of clinicopathological factors associated with TILs could help clinicians to understand the tumor immunity of BRCA and improve treatment system for patients, and the established nomogram with high evaluation efficiency may be used as a complement tool for distinguishing patients with better NAT efficacy.
format	article
author	Jikun Feng Jianxia Li Xinjian Huang Jiarong Yi Haoming Wu Xuxiazi Zou Wenjing Zhong Xi Wang
author_facet	Jikun Feng Jianxia Li Xinjian Huang Jiarong Yi Haoming Wu Xuxiazi Zou Wenjing Zhong Xi Wang
author_sort	Jikun Feng
title	Nomogram to Predict Tumor-Infiltrating Lymphocytes in Breast Cancer Patients
title_short	Nomogram to Predict Tumor-Infiltrating Lymphocytes in Breast Cancer Patients
title_full	Nomogram to Predict Tumor-Infiltrating Lymphocytes in Breast Cancer Patients
title_fullStr	Nomogram to Predict Tumor-Infiltrating Lymphocytes in Breast Cancer Patients
title_full_unstemmed	Nomogram to Predict Tumor-Infiltrating Lymphocytes in Breast Cancer Patients
title_sort	nomogram to predict tumor-infiltrating lymphocytes in breast cancer patients
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/cfb8afe998404d68baab4fc96458d811
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Nomogram to Predict Tumor-Infiltrating Lymphocytes in Breast Cancer Patients

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