The prognostic model and immune landscape based on cancer-associated fibroblast features for patients with locally advanced rectal cancer

Background: This study aimed to construct a nomogram based on CAF features to predict the cancer-specific survival (CSS) rates of locally advanced rectal cancer (LARC) patients. Methods: The EPIC algorithm was employed to calculate the proportion of CAFs. based on the differentially expressed genes...

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Main Authors: Huajun Cai, Yijuan Lin, Yong Wu, Ye Wang, Shoufeng Li, Yiyi Zhang, Jinfu Zhuang, Xing Liu, Guoxian Guan
Format: Article
Language:English
Published: Elsevier 2024-04-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844024047042
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author Huajun Cai
Yijuan Lin
Yong Wu
Ye Wang
Shoufeng Li
Yiyi Zhang
Jinfu Zhuang
Xing Liu
Guoxian Guan
author_facet Huajun Cai
Yijuan Lin
Yong Wu
Ye Wang
Shoufeng Li
Yiyi Zhang
Jinfu Zhuang
Xing Liu
Guoxian Guan
author_sort Huajun Cai
collection DOAJ
description Background: This study aimed to construct a nomogram based on CAF features to predict the cancer-specific survival (CSS) rates of locally advanced rectal cancer (LARC) patients. Methods: The EPIC algorithm was employed to calculate the proportion of CAFs. based on the differentially expressed genes between the high and low CAF proportion subgroups, prognostic genes were identified via LASSO and Cox regression analyses. They were then used to construct a prognostic risk signature. Moreover, the GSE39582 and GGSE38832 datasets were used for external validation. Lastly, the level of immune infiltration was evaluated using ssGSEA, ESTIMATE, CIBERSORTx, and TIMER. Results: A higher level of CAF infiltration was associated with a worse prognosis. Additionally, the number of metastasized lymph nodes and distant metastases, as well as the level of immune infiltration were higher in the high CAF proportion subgroup. Five prognostic genes (SMOC2, TUBAL3, C2CD4A, MAP1B, BMP8A) were identified and subsequently incorporated into the prognostic risk signature to predict the 1-, 3-, and 5-year CSS rates in the training and validation sets. Differences in survival rates were also determined in the external validation cohort. Furthermore, independent prognostic factors, including TNM stage and risk score, were combined to established a nomogram. Notably, our results revealed that the proportions of macrophages and neutrophils and the levels of cytokines secreted by M2 macrophages were higher in the high-risk subgroup. Finally, the prognostic genes were significantly associated with the level of immune cell infiltration. Conclusion: Herein, a nomogram based on CAF features was developed to predict the CSS rate of LARC patients. The risk model was capable of reflecting differences in the level of immune cell infiltration.
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spelling doaj.art-6f3d98e4ef024469b1b0fbfff75cfef52024-03-29T05:50:46ZengElsevierHeliyon2405-84402024-04-01107e28673The prognostic model and immune landscape based on cancer-associated fibroblast features for patients with locally advanced rectal cancerHuajun Cai0Yijuan Lin1Yong Wu2Ye Wang3Shoufeng Li4Yiyi Zhang5Jinfu Zhuang6Xing Liu7Guoxian Guan8Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaDepartment of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaDepartment of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaDepartment of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaDepartment of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaDepartment of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaDepartment of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaDepartment of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Department of Colorectal Surgery, National Regional Medical Center, Binhai Campus of The First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Corresponding author.Background: This study aimed to construct a nomogram based on CAF features to predict the cancer-specific survival (CSS) rates of locally advanced rectal cancer (LARC) patients. Methods: The EPIC algorithm was employed to calculate the proportion of CAFs. based on the differentially expressed genes between the high and low CAF proportion subgroups, prognostic genes were identified via LASSO and Cox regression analyses. They were then used to construct a prognostic risk signature. Moreover, the GSE39582 and GGSE38832 datasets were used for external validation. Lastly, the level of immune infiltration was evaluated using ssGSEA, ESTIMATE, CIBERSORTx, and TIMER. Results: A higher level of CAF infiltration was associated with a worse prognosis. Additionally, the number of metastasized lymph nodes and distant metastases, as well as the level of immune infiltration were higher in the high CAF proportion subgroup. Five prognostic genes (SMOC2, TUBAL3, C2CD4A, MAP1B, BMP8A) were identified and subsequently incorporated into the prognostic risk signature to predict the 1-, 3-, and 5-year CSS rates in the training and validation sets. Differences in survival rates were also determined in the external validation cohort. Furthermore, independent prognostic factors, including TNM stage and risk score, were combined to established a nomogram. Notably, our results revealed that the proportions of macrophages and neutrophils and the levels of cytokines secreted by M2 macrophages were higher in the high-risk subgroup. Finally, the prognostic genes were significantly associated with the level of immune cell infiltration. Conclusion: Herein, a nomogram based on CAF features was developed to predict the CSS rate of LARC patients. The risk model was capable of reflecting differences in the level of immune cell infiltration.http://www.sciencedirect.com/science/article/pii/S2405844024047042Cancer-associated fibroblastsLocally advanced rectal cancerPrognostic risk signatureNomogramImmune landscape
spellingShingle Huajun Cai
Yijuan Lin
Yong Wu
Ye Wang
Shoufeng Li
Yiyi Zhang
Jinfu Zhuang
Xing Liu
Guoxian Guan
The prognostic model and immune landscape based on cancer-associated fibroblast features for patients with locally advanced rectal cancer
Heliyon
Cancer-associated fibroblasts
Locally advanced rectal cancer
Prognostic risk signature
Nomogram
Immune landscape
title The prognostic model and immune landscape based on cancer-associated fibroblast features for patients with locally advanced rectal cancer
title_full The prognostic model and immune landscape based on cancer-associated fibroblast features for patients with locally advanced rectal cancer
title_fullStr The prognostic model and immune landscape based on cancer-associated fibroblast features for patients with locally advanced rectal cancer
title_full_unstemmed The prognostic model and immune landscape based on cancer-associated fibroblast features for patients with locally advanced rectal cancer
title_short The prognostic model and immune landscape based on cancer-associated fibroblast features for patients with locally advanced rectal cancer
title_sort prognostic model and immune landscape based on cancer associated fibroblast features for patients with locally advanced rectal cancer
topic Cancer-associated fibroblasts
Locally advanced rectal cancer
Prognostic risk signature
Nomogram
Immune landscape
url http://www.sciencedirect.com/science/article/pii/S2405844024047042
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