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Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Artificial Intelligence | Research

An artificial intelligence-based ecological index for prognostic evaluation of colorectal cancer

Authors: Qicong Chen, Ming Cai, Xinjuan Fan, Wenbin Liu, Gang Fang, Su Yao, Yao Xu, Qian Li, Yingnan Zhao, Ke Zhao, Zaiyi Liu, Zhihua Chen

Published in: BMC Cancer | Issue 1/2023

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Abstract

Background and objective

In the tumor microenvironment (TME), the dynamic interaction between tumor cells and immune cells plays a critical role in predicting the prognosis of colorectal cancer. This study introduces a novel approach based on artificial intelligence (AI) and immunohistochemistry (IHC)-stained whole-slide images (WSIs) of colorectal cancer (CRC) patients to quantitatively assess the spatial associations between tumor cells and immune cells. To achieve this, we employ the Morisita-Horn ecological index (Mor-index), which allows for a comprehensive analysis of the spatial distribution patterns between tumor cells and immune cells within the TME.

Materials and methods

In this study, we employed a combination of deep learning technology and traditional computer segmentation methods to accurately segment the tumor nuclei, immune nuclei, and stroma nuclei within the tumor regions of IHC-stained WSIs. The Mor-index was used to assess the spatial association between tumor cells and immune cells in TME of CRC patients by obtaining the results of cell nuclei segmentation. A discovery cohort (N = 432) and validation cohort (N = 137) were used to evaluate the prognostic value of the Mor-index for overall survival (OS).

Results

The efficacy of our method was demonstrated through experiments conducted on two datasets comprising a total of 569 patients. Compared to other studies, our method is not only superior to the QuPath tool but also produces better segmentation results with an accuracy of 0.85. Mor-index was quantified automatically by our method. Survival analysis indicated that the higher Mor-index correlated with better OS in the discovery cohorts (HR for high vs. low 0.49, 95% CI 0.27–0.77, P = 0.0014) and validation cohort (0.21, 0.10–0.46, < 0.0001).

Conclusion

This study provided a novel AI-based approach to segmenting various nuclei in the TME. The Mor-index can reflect the immune status of CRC patients and is associated with favorable survival. Thus, Mor-index can potentially make a significant role in aiding clinical prognosis and decision-making.
Literature
1.
go back to reference Hossain MDS, Karuniawati H, Jairoun AA, Urbi Z, Ooi DJ, John A, et al. Colorectal cancer: a review of carcinogenesis, global epidemiology, current challenges, risk factors, preventive and treatment strategies. Cancers. 2022;14(7):1732.CrossRefPubMedPubMedCentral Hossain MDS, Karuniawati H, Jairoun AA, Urbi Z, Ooi DJ, John A, et al. Colorectal cancer: a review of carcinogenesis, global epidemiology, current challenges, risk factors, preventive and treatment strategies. Cancers. 2022;14(7):1732.CrossRefPubMedPubMedCentral
2.
go back to reference Ribeiro Franco PI, Rodrigues AP, de Menezes LB, Pacheco MM. Tumor microenvironment components: Allies of cancer progression. Pathol Res Pract. 2020;216(1):152729.CrossRefPubMed Ribeiro Franco PI, Rodrigues AP, de Menezes LB, Pacheco MM. Tumor microenvironment components: Allies of cancer progression. Pathol Res Pract. 2020;216(1):152729.CrossRefPubMed
4.
go back to reference Giraldo NA, Sanchez-Salas R, Peske JD, Vano Y, Becht E, Petitprez F, et al. The clinical role of the TME in solid cancer. Br J Cancer. 2019;120(1):45–53.CrossRefPubMed Giraldo NA, Sanchez-Salas R, Peske JD, Vano Y, Becht E, Petitprez F, et al. The clinical role of the TME in solid cancer. Br J Cancer. 2019;120(1):45–53.CrossRefPubMed
5.
go back to reference Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pagès C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313(5795):1960–4.CrossRefPubMed Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pagès C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313(5795):1960–4.CrossRefPubMed
6.
go back to reference Scheper W, Kelderman S, Fanchi LF, Linnemann C, Bendle G, de Rooij MAJ, et al. Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers. Nat Med. 2019;25(1):89–94.CrossRefPubMed Scheper W, Kelderman S, Fanchi LF, Linnemann C, Bendle G, de Rooij MAJ, et al. Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers. Nat Med. 2019;25(1):89–94.CrossRefPubMed
7.
go back to reference Idos GE, Kwok J, Bonthala N, Kysh L, Gruber SB, Qu C. The prognostic implications of tumor infiltrating lymphocytes in colorectal cancer: a systematic review and meta-analysis. Sci Rep. 2020;10(1):3360.CrossRefPubMedPubMedCentral Idos GE, Kwok J, Bonthala N, Kysh L, Gruber SB, Qu C. The prognostic implications of tumor infiltrating lymphocytes in colorectal cancer: a systematic review and meta-analysis. Sci Rep. 2020;10(1):3360.CrossRefPubMedPubMedCentral
8.
go back to reference Giraldo NA, Becht E, Remark R, Damotte D, Sautès-Fridman C, Fridman WH. The immune contexture of primary and metastatic human tumours. Curr Opin Immunol. 2014;27:8–15.CrossRefPubMed Giraldo NA, Becht E, Remark R, Damotte D, Sautès-Fridman C, Fridman WH. The immune contexture of primary and metastatic human tumours. Curr Opin Immunol. 2014;27:8–15.CrossRefPubMed
9.
go back to reference Issa-Nummer Y, Darb-Esfahani S, Loibl S, Kunz G, Nekljudova V, Schrader I, et al. Prospective Validation of Immunological Infiltrate for Prediction of Response to Neoadjuvant Chemotherapy in HER2-Negative Breast Cancer – A Substudy of the Neoadjuvant GeparQuinto Trial. Glynn SA, editor. PLoS One. 2013;8(12):e79775.CrossRefPubMedPubMedCentral Issa-Nummer Y, Darb-Esfahani S, Loibl S, Kunz G, Nekljudova V, Schrader I, et al. Prospective Validation of Immunological Infiltrate for Prediction of Response to Neoadjuvant Chemotherapy in HER2-Negative Breast Cancer – A Substudy of the Neoadjuvant GeparQuinto Trial. Glynn SA, editor. PLoS One. 2013;8(12):e79775.CrossRefPubMedPubMedCentral
10.
go back to reference Maley CC, Koelble K, Natrajan R, Aktipis A, Yuan Y. An ecological measure of immune-cancer colocalization as a prognostic factor for breast cancer. Breast Cancer Res. 2015;17(1):131.CrossRefPubMedPubMedCentral Maley CC, Koelble K, Natrajan R, Aktipis A, Yuan Y. An ecological measure of immune-cancer colocalization as a prognostic factor for breast cancer. Breast Cancer Res. 2015;17(1):131.CrossRefPubMedPubMedCentral
11.
go back to reference Ugai T, Haruki K, Väyrynen JP, Zhong R, Borowsky J, Fujiyoshi K, et al. Coffee intake and colorectal cancer oncidence according to T-Cell response. JNCI Cancer Spectrum. 2020;4(6):pkaa068.CrossRefPubMedPubMedCentral Ugai T, Haruki K, Väyrynen JP, Zhong R, Borowsky J, Fujiyoshi K, et al. Coffee intake and colorectal cancer oncidence according to T-Cell response. JNCI Cancer Spectrum. 2020;4(6):pkaa068.CrossRefPubMedPubMedCentral
12.
go back to reference Halama N, Spille A, Lerchl T, Brand K, Herpel E, Welte S, et al. Hepatic metastases of colorectal cancer are rather homogeneous but differ from primary lesions in terms of immune cell infiltration. OncoImmunology. 2013;2(4):e24116.CrossRefPubMedPubMedCentral Halama N, Spille A, Lerchl T, Brand K, Herpel E, Welte S, et al. Hepatic metastases of colorectal cancer are rather homogeneous but differ from primary lesions in terms of immune cell infiltration. OncoImmunology. 2013;2(4):e24116.CrossRefPubMedPubMedCentral
13.
go back to reference Schnellhardt S, Hirneth J, Büttner-Herold M, Daniel C, Haderlein M, Hartmann A, et al. The Prognostic Value of FoxP3+ Tumour-Infiltrating Lymphocytes in Rectal Cancer Depends on Immune Phenotypes Defined by CD8+ Cytotoxic T Cell Density. Front Immunol. 2022;24(13):781222.CrossRef Schnellhardt S, Hirneth J, Büttner-Herold M, Daniel C, Haderlein M, Hartmann A, et al. The Prognostic Value of FoxP3+ Tumour-Infiltrating Lymphocytes in Rectal Cancer Depends on Immune Phenotypes Defined by CD8+ Cytotoxic T Cell Density. Front Immunol. 2022;24(13):781222.CrossRef
14.
go back to reference Fakih M, Ouyang C, Wang C, Tu TY, Gozo MC, Cho M, et al. Immune overdrive signature in colorectal tumor subset predicts poor clinical outcome. J Clin Investig. 2019;129(10):4464–76.CrossRefPubMedPubMedCentral Fakih M, Ouyang C, Wang C, Tu TY, Gozo MC, Cho M, et al. Immune overdrive signature in colorectal tumor subset predicts poor clinical outcome. J Clin Investig. 2019;129(10):4464–76.CrossRefPubMedPubMedCentral
16.
go back to reference Alagappan M, Brown JRG, Mori Y, Berzin TM. Artificial intelligence in gastrointestinal endoscopy: The future is almost here. WJGE. 2018;10(10):239–49.CrossRefPubMedPubMedCentral Alagappan M, Brown JRG, Mori Y, Berzin TM. Artificial intelligence in gastrointestinal endoscopy: The future is almost here. WJGE. 2018;10(10):239–49.CrossRefPubMedPubMedCentral
17.
go back to reference Zhao K, Wu X, Li Z, Wang Y, Xu Z, Li Y, et al. Prognostic value of a modified Immunosocre in patients with stage I−III resectable colon cancer. Chin J Cancer Res. 2021;33(3):379–90.CrossRefPubMedPubMedCentral Zhao K, Wu X, Li Z, Wang Y, Xu Z, Li Y, et al. Prognostic value of a modified Immunosocre in patients with stage I−III resectable colon cancer. Chin J Cancer Res. 2021;33(3):379–90.CrossRefPubMedPubMedCentral
18.
go back to reference Zhao K, Li Z, Yao S, Wang Y, Wu X, Xu Z, et al. Artificial intelligence quantified tumour-stroma ratio is an independent predictor for overall survival in resectable colorectal cancer. EBioMedicine. 2020;61:103054.CrossRefPubMedPubMedCentral Zhao K, Li Z, Yao S, Wang Y, Wu X, Xu Z, et al. Artificial intelligence quantified tumour-stroma ratio is an independent predictor for overall survival in resectable colorectal cancer. EBioMedicine. 2020;61:103054.CrossRefPubMedPubMedCentral
19.
go back to reference Jain AK, Farrokhnia F. Unsupervised texture segmentation using Gabor filters[J]. Pattern Recognit. 1991;24(12):1167–86. Jain AK, Farrokhnia F. Unsupervised texture segmentation using Gabor filters[J]. Pattern Recognit. 1991;24(12):1167–86.
20.
go back to reference Rempala GA, Seweryn M. Methods for diversity and overlap analysis in T-cell receptor populations[J]. J Math Biol. 2013;67(6-7):1339–68. Rempala GA, Seweryn M. Methods for diversity and overlap analysis in T-cell receptor populations[J]. J Math Biol. 2013;67(6-7):1339–68.
21.
go back to reference Scalon JD, Avelar MBL, Alves G de F, Zacarias MS. Spatial and temporal dynamics of coffee-leaf-miner and predatory wasps in organic coffee field in formation. Cienc Rural. 2011;41(4):646–52.CrossRef Scalon JD, Avelar MBL, Alves G de F, Zacarias MS. Spatial and temporal dynamics of coffee-leaf-miner and predatory wasps in organic coffee field in formation. Cienc Rural. 2011;41(4):646–52.CrossRef
23.
go back to reference Bense RD, Sotiriou C, Piccart-Gebhart MJ, Haanen JBAG, van Vugt MATM, de Vries EGE, et al. Relevance of Tumor-Infiltrating Immune Cell Composition and Functionality for Disease Outcome in Breast Cancer. JNCI J Natl Cancer Inst. 2017;109(1):djw192.CrossRefPubMed Bense RD, Sotiriou C, Piccart-Gebhart MJ, Haanen JBAG, van Vugt MATM, de Vries EGE, et al. Relevance of Tumor-Infiltrating Immune Cell Composition and Functionality for Disease Outcome in Breast Cancer. JNCI J Natl Cancer Inst. 2017;109(1):djw192.CrossRefPubMed
24.
go back to reference Donnem T, Kilvaer TK, Andersen S, Richardsen E, Paulsen EE, Hald SM, et al. Strategies for clinical implementation of TNM-Immunoscore in resected nonsmall-cell lung cancer. Ann Oncol. 2016;27(2):225–32.CrossRefPubMed Donnem T, Kilvaer TK, Andersen S, Richardsen E, Paulsen EE, Hald SM, et al. Strategies for clinical implementation of TNM-Immunoscore in resected nonsmall-cell lung cancer. Ann Oncol. 2016;27(2):225–32.CrossRefPubMed
25.
go back to reference Rempa GA. Methods for diversity and overlap analysis in T-cell receptor populations. 2014;31. Rempa GA. Methods for diversity and overlap analysis in T-cell receptor populations. 2014;31.
26.
go back to reference Ji X, Li Y, Cheng J, Yu Y, Wang M. Cell image segmentation based on an improved watershed algorithm. In: 2015 8th International Congress on Image and Signal Processing (CISP). Shenyang, China: IEEE; 2015. p. 433–7. Available from: http://ieeexplore.ieee.org/document/7407919/. [Cited 2022 May 14]. Ji X, Li Y, Cheng J, Yu Y, Wang M. Cell image segmentation based on an improved watershed algorithm. In: 2015 8th International Congress on Image and Signal Processing (CISP). Shenyang, China: IEEE; 2015. p. 433–7. Available from: http://​ieeexplore.​ieee.​org/​document/​7407919/​. [Cited 2022 May 14].
28.
go back to reference O’Connor JPB, Rose CJ, Waterton JC, Carano RAD, Parker JM, Jackson A. Imaging intratumor heterogeneity: role in therapy response, resistance, and clinical outcome. Clin Cancer Res. 2015;19:249–57.CrossRef O’Connor JPB, Rose CJ, Waterton JC, Carano RAD, Parker JM, Jackson A. Imaging intratumor heterogeneity: role in therapy response, resistance, and clinical outcome. Clin Cancer Res. 2015;19:249–57.CrossRef
Metadata
Title
An artificial intelligence-based ecological index for prognostic evaluation of colorectal cancer
Authors
Qicong Chen
Ming Cai
Xinjuan Fan
Wenbin Liu
Gang Fang
Su Yao
Yao Xu
Qian Li
Yingnan Zhao
Ke Zhao
Zaiyi Liu
Zhihua Chen
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-11289-0

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