Identification and Validation of a Six Immune-Related Genes Signature for Predicting Prognosis in Patients With Stage II Colorectal Cancer
BackgroundImmune-related genes (IRGs) play important roles in the tumor immune microenvironment and can affect the prognosis of cancer. This study aimed to construct a novel IRG signature for prognostic evaluation of stage II colorectal cancer (CRC).MethodsGene expression profiles and clinical data...
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.666003/full |
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| author | Xianzhe Li Xianzhe Li Minghao Xie Minghao Xie Shi Yin Shi Yin Zhizhong Xiong Zhizhong Xiong Chaobin Mao Fengxiang Zhang Huaxian Chen Huaxian Chen Longyang Jin Ping Lan Ping Lan Lei Lian Lei Lian |
| author_facet | Xianzhe Li Xianzhe Li Minghao Xie Minghao Xie Shi Yin Shi Yin Zhizhong Xiong Zhizhong Xiong Chaobin Mao Fengxiang Zhang Huaxian Chen Huaxian Chen Longyang Jin Ping Lan Ping Lan Lei Lian Lei Lian |
| author_sort | Xianzhe Li |
| collection | DOAJ |
| description | BackgroundImmune-related genes (IRGs) play important roles in the tumor immune microenvironment and can affect the prognosis of cancer. This study aimed to construct a novel IRG signature for prognostic evaluation of stage II colorectal cancer (CRC).MethodsGene expression profiles and clinical data for stage II CRC patients were collected from the Cancer Genome Atlas and Gene Expression Omnibus database. Univariate, multivariate Cox regression, and least absolute shrinkage and selection operator regression were used to develop the IRG signature, namely IRGCRCII. A nomogram was constructed, and the “Cell Type Identification by Estimating Relative Subsets of RNA Transcripts” (CIBERSORT) method was used to estimate immune cell infiltration. The expression levels of genes and proteins were validated by qRT-PCR and immunohistochemistry in 30 pairs of primary stage II CRC and matched normal tissues.ResultsA total of 466 patients with stage II CRC were included, and 274 differentially expressed IRGs were identified. Six differentially expressed IRGs were detected and used to construct the IRGCRCII signature, which could significantly stratify patients into high-risk and low-risk groups in terms of disease-free survival in three cohorts: training, test, and external validation (GSE39582). Receiver operating characteristics analysis revealed that the area under the curves of the IRGCRCII signature were significantly greater than those of the OncotypeDX colon signature at 1 (0.759 vs. 0.623), 3 (0.875 vs. 0.629), and 5 years (0.906 vs. 0.698) disease-free survival, respectively. The nomogram performed well in the concordance index (0.779) and calibration curves. The high-risk group had a significantly higher percentage of infiltrated immune cells (e.g., M2 macrophages, plasma cells, resting mast cells) than the low-risk group. Finally, the results of qRT-PCR and immunohistochemistry experiments performed on 30 pairs of clinical specimens were consistent with bioinformatics analysis.ConclusionThis study developed and validated a novel immune prognostic signature based on six differentially expressed IRGs for predicting disease-free survival and immune status in patients with stage II CRC, which may reflect immune dysregulation in the tumor immune microenvironment. |
| first_indexed | 2024-12-16T23:58:25Z |
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| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-16T23:58:25Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-ef5e4ee3eca040d7bd805df4235e60672022-12-21T22:11:09ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-05-011210.3389/fgene.2021.666003666003Identification and Validation of a Six Immune-Related Genes Signature for Predicting Prognosis in Patients With Stage II Colorectal CancerXianzhe Li0Xianzhe Li1Minghao Xie2Minghao Xie3Shi Yin4Shi Yin5Zhizhong Xiong6Zhizhong Xiong7Chaobin Mao8Fengxiang Zhang9Huaxian Chen10Huaxian Chen11Longyang Jin12Ping Lan13Ping Lan14Lei Lian15Lei Lian16Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaBackgroundImmune-related genes (IRGs) play important roles in the tumor immune microenvironment and can affect the prognosis of cancer. This study aimed to construct a novel IRG signature for prognostic evaluation of stage II colorectal cancer (CRC).MethodsGene expression profiles and clinical data for stage II CRC patients were collected from the Cancer Genome Atlas and Gene Expression Omnibus database. Univariate, multivariate Cox regression, and least absolute shrinkage and selection operator regression were used to develop the IRG signature, namely IRGCRCII. A nomogram was constructed, and the “Cell Type Identification by Estimating Relative Subsets of RNA Transcripts” (CIBERSORT) method was used to estimate immune cell infiltration. The expression levels of genes and proteins were validated by qRT-PCR and immunohistochemistry in 30 pairs of primary stage II CRC and matched normal tissues.ResultsA total of 466 patients with stage II CRC were included, and 274 differentially expressed IRGs were identified. Six differentially expressed IRGs were detected and used to construct the IRGCRCII signature, which could significantly stratify patients into high-risk and low-risk groups in terms of disease-free survival in three cohorts: training, test, and external validation (GSE39582). Receiver operating characteristics analysis revealed that the area under the curves of the IRGCRCII signature were significantly greater than those of the OncotypeDX colon signature at 1 (0.759 vs. 0.623), 3 (0.875 vs. 0.629), and 5 years (0.906 vs. 0.698) disease-free survival, respectively. The nomogram performed well in the concordance index (0.779) and calibration curves. The high-risk group had a significantly higher percentage of infiltrated immune cells (e.g., M2 macrophages, plasma cells, resting mast cells) than the low-risk group. Finally, the results of qRT-PCR and immunohistochemistry experiments performed on 30 pairs of clinical specimens were consistent with bioinformatics analysis.ConclusionThis study developed and validated a novel immune prognostic signature based on six differentially expressed IRGs for predicting disease-free survival and immune status in patients with stage II CRC, which may reflect immune dysregulation in the tumor immune microenvironment.https://www.frontiersin.org/articles/10.3389/fgene.2021.666003/fullcolorectal cancerimmune-related genesprognosisstage IItumor immune microenvironment |
| spellingShingle | Xianzhe Li Xianzhe Li Minghao Xie Minghao Xie Shi Yin Shi Yin Zhizhong Xiong Zhizhong Xiong Chaobin Mao Fengxiang Zhang Huaxian Chen Huaxian Chen Longyang Jin Ping Lan Ping Lan Lei Lian Lei Lian Identification and Validation of a Six Immune-Related Genes Signature for Predicting Prognosis in Patients With Stage II Colorectal Cancer Frontiers in Genetics colorectal cancer immune-related genes prognosis stage II tumor immune microenvironment |
| title | Identification and Validation of a Six Immune-Related Genes Signature for Predicting Prognosis in Patients With Stage II Colorectal Cancer |
| title_full | Identification and Validation of a Six Immune-Related Genes Signature for Predicting Prognosis in Patients With Stage II Colorectal Cancer |
| title_fullStr | Identification and Validation of a Six Immune-Related Genes Signature for Predicting Prognosis in Patients With Stage II Colorectal Cancer |
| title_full_unstemmed | Identification and Validation of a Six Immune-Related Genes Signature for Predicting Prognosis in Patients With Stage II Colorectal Cancer |
| title_short | Identification and Validation of a Six Immune-Related Genes Signature for Predicting Prognosis in Patients With Stage II Colorectal Cancer |
| title_sort | identification and validation of a six immune related genes signature for predicting prognosis in patients with stage ii colorectal cancer |
| topic | colorectal cancer immune-related genes prognosis stage II tumor immune microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.666003/full |
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