HOXC6: A promising biomarker linked to an immunoevasive microenvironment in colorectal cancer based on TCGA analysis and cohort validation
HOXC6 plays an essential part of the carcinogenesis of solid tumors, but its functional relevance within the immune contexture in patients with colorectal cancer (CRC) is still uncertain. We intended to investigate the predictive value of HOXC6 expression for survival outcomes and its correlation wi...
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| Format: | Article |
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Elsevier
2024-01-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023107080 |
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| author | Meilin Weng Yuling Lai Xiaodong Ge Wenchao Gu Xixue Zhang Lihong Li Minli Sun |
| author_facet | Meilin Weng Yuling Lai Xiaodong Ge Wenchao Gu Xixue Zhang Lihong Li Minli Sun |
| author_sort | Meilin Weng |
| collection | DOAJ |
| description | HOXC6 plays an essential part of the carcinogenesis of solid tumors, but its functional relevance within the immune contexture in patients with colorectal cancer (CRC) is still uncertain. We intended to investigate the predictive value of HOXC6 expression for survival outcomes and its correlation with immune contexture in CRC patients by utilizing the Cancer Genome Atlas database (n = 619). Validation was performed in cohorts from Zhongshan Hospital (n = 200) and Shanghai Cancer Center (n = 300). Immunohistochemical (IHC) staining was utilized to compare the levels of immunocytes infiltrating the tumor between the groups with high and low expression of HOXC6. Elevated levels of HOXC6 expression in CRC tissues were linked to malignant progression and poor prognosis. HOXC6 as a risk factor for survival of CRC patients was confirmed. Receiver operating characteristic analysis confirmed its diagnostic value, and a reliable prognostic nomogram was constructed. KEGG analysis and GSEA showed that HOXC6 participated in immune regulation, and its expression was tightly linked to the abundance of infiltrating immunocytes. HOXC6 was upregulated in patients diagnosed with CRC within the two cohorts, and high HOXC6 levels were correlated with a worse prognosis. The high-HOXC6 expression group showed increased infiltration of Treg cells, CD68+ macrophages, CD66b+ neutrophils, and CD8+ T-cells and elevated levels of PD-L1 and PD-1, but decreased levels of granzyme B and perforin. These findings suggest that HOXC6 abundance in patients with CRC determines a poor prognosis, promotes an immunoevasive environment, and directs CD8+ T-cell dysfunction. HOXC6 is expected to become a prospective biomarker for the outcome of CRC. |
| first_indexed | 2024-03-08T09:03:21Z |
| format | Article |
| id | doaj.art-4d7666128aef4570b6f1d89aadfb6b02 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-08T09:03:21Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-4d7666128aef4570b6f1d89aadfb6b022024-02-01T06:32:09ZengElsevierHeliyon2405-84402024-01-01101e23500HOXC6: A promising biomarker linked to an immunoevasive microenvironment in colorectal cancer based on TCGA analysis and cohort validationMeilin Weng0Yuling Lai1Xiaodong Ge2Wenchao Gu3Xixue Zhang4Lihong Li5Minli Sun6Department of Anesthesiology, Zhongshan hospital, Fudan University, Shanghai, 200032, China; Shanghai Key Laboratory of Perioperative Stress and Protection, Zhongshan hospital, Fudan University, Shanghai, 200032, ChinaDepartment of Anesthesiology, Zhongshan hospital, Fudan University, Shanghai, 200032, China; Shanghai Key Laboratory of Perioperative Stress and Protection, Zhongshan hospital, Fudan University, Shanghai, 200032, ChinaDepartment of Anesthesiology, Zhongshan hospital, Fudan University, Shanghai, 200032, China; Shanghai Key Laboratory of Perioperative Stress and Protection, Zhongshan hospital, Fudan University, Shanghai, 200032, ChinaDepartment of Diagnostic and Interventional Radiology, University of Tsukuba, Faculty of medicine, Ibaraki, Tsukuba, JapanDepartment of Anesthesiology, Huadong Hospital Affiliated to Fudan University, No 221, West Yan'an Road, Shanghai 200040, China; Corresponding author.Department of Anesthesiology, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China; Corresponding author. Department of Anesthesiology, Fifth floor, No.8 Building, No.180 Fenglin Road, Shanghai 200032, China.Department of Anesthesiology, Zhongshan hospital, Fudan University, Shanghai, 200032, China; Shanghai Key Laboratory of Perioperative Stress and Protection, Zhongshan hospital, Fudan University, Shanghai, 200032, China; Corresponding author. Department of Anesthesiology, Zhongshan hospital, Fudan University, No.180 Fenglin Road, Shanghai 200032, China.HOXC6 plays an essential part of the carcinogenesis of solid tumors, but its functional relevance within the immune contexture in patients with colorectal cancer (CRC) is still uncertain. We intended to investigate the predictive value of HOXC6 expression for survival outcomes and its correlation with immune contexture in CRC patients by utilizing the Cancer Genome Atlas database (n = 619). Validation was performed in cohorts from Zhongshan Hospital (n = 200) and Shanghai Cancer Center (n = 300). Immunohistochemical (IHC) staining was utilized to compare the levels of immunocytes infiltrating the tumor between the groups with high and low expression of HOXC6. Elevated levels of HOXC6 expression in CRC tissues were linked to malignant progression and poor prognosis. HOXC6 as a risk factor for survival of CRC patients was confirmed. Receiver operating characteristic analysis confirmed its diagnostic value, and a reliable prognostic nomogram was constructed. KEGG analysis and GSEA showed that HOXC6 participated in immune regulation, and its expression was tightly linked to the abundance of infiltrating immunocytes. HOXC6 was upregulated in patients diagnosed with CRC within the two cohorts, and high HOXC6 levels were correlated with a worse prognosis. The high-HOXC6 expression group showed increased infiltration of Treg cells, CD68+ macrophages, CD66b+ neutrophils, and CD8+ T-cells and elevated levels of PD-L1 and PD-1, but decreased levels of granzyme B and perforin. These findings suggest that HOXC6 abundance in patients with CRC determines a poor prognosis, promotes an immunoevasive environment, and directs CD8+ T-cell dysfunction. HOXC6 is expected to become a prospective biomarker for the outcome of CRC.http://www.sciencedirect.com/science/article/pii/S2405844023107080HOXC6BiomarkerImmunoevasivetumor microenvironmentColorectal cancerTCGA |
| spellingShingle | Meilin Weng Yuling Lai Xiaodong Ge Wenchao Gu Xixue Zhang Lihong Li Minli Sun HOXC6: A promising biomarker linked to an immunoevasive microenvironment in colorectal cancer based on TCGA analysis and cohort validation Heliyon HOXC6 Biomarker Immunoevasive tumor microenvironment Colorectal cancer TCGA |
| title | HOXC6: A promising biomarker linked to an immunoevasive microenvironment in colorectal cancer based on TCGA analysis and cohort validation |
| title_full | HOXC6: A promising biomarker linked to an immunoevasive microenvironment in colorectal cancer based on TCGA analysis and cohort validation |
| title_fullStr | HOXC6: A promising biomarker linked to an immunoevasive microenvironment in colorectal cancer based on TCGA analysis and cohort validation |
| title_full_unstemmed | HOXC6: A promising biomarker linked to an immunoevasive microenvironment in colorectal cancer based on TCGA analysis and cohort validation |
| title_short | HOXC6: A promising biomarker linked to an immunoevasive microenvironment in colorectal cancer based on TCGA analysis and cohort validation |
| title_sort | hoxc6 a promising biomarker linked to an immunoevasive microenvironment in colorectal cancer based on tcga analysis and cohort validation |
| topic | HOXC6 Biomarker Immunoevasive tumor microenvironment Colorectal cancer TCGA |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023107080 |
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