Effects of somatic alterations at pathway level are more mechanism‐explanatory and clinically applicable to quantity of liver metastases of colorectal cancer
Abstract Background The quantity of metastases lesions is an important reference when it comes to making a more informed treatment decision for patients with colorectal cancer liver metastases. However, the molecular alterations in patients with different numbers of lesions have not been systematica...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-08-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.2368 |
| _version_ | 1797847649806712832 |
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| author | Zhong‐guo Zhang Fei Ma Shuang Zhao Xiaoyu Yang Fang Liu Chenghai Xue Liren Liu Jin Gu Haozhe Piao |
| author_facet | Zhong‐guo Zhang Fei Ma Shuang Zhao Xiaoyu Yang Fang Liu Chenghai Xue Liren Liu Jin Gu Haozhe Piao |
| author_sort | Zhong‐guo Zhang |
| collection | DOAJ |
| description | Abstract Background The quantity of metastases lesions is an important reference when it comes to making a more informed treatment decision for patients with colorectal cancer liver metastases. However, the molecular alterations in patients with different numbers of lesions have not been systematically studied. Methods We investigated somatic alterations and microsatellite instability (MSI) of liver metastases from patients with single, multiple or diffuse metastasis lesions. A new algorithm “Pathway Damage Score” was developed to comprehensively assess the functional impact of somatic alterations at the pathway level. Pathogenic pathways of different metastasis were identified and their prognosis effects were evaluated. Furthermore, the subnetworks and affected phenotypes of the altered genes in each pathogenic pathway were analyzed. Results Somatic alterations and altered genes occurred sporadically as well as in MSI state in different metastasis types, although MSS patients had more metastatic lesions than that of the MSI patients. Every metastasis group has their own pathogenic pathways and damaged “Cargo recognition for clathrin‐mediated endocytosis” is significantly associated with poor prognosis (P < 0.001). Further pathway subnetwork analysis showed that except conventional drivers, other genes could also contribute to metastasis formation. Conclusions Progression of liver metastasis could be driven by the coefficient of all altered genes belonging to the pathways. Thus, compared to somatic alterations and genes, pathway level analysis is more reasonable for functional interpretations of molecular alterations in clinical samples. |
| first_indexed | 2024-04-09T18:15:58Z |
| format | Article |
| id | doaj.art-b33be7c69f554cc291104e8c2d841b75 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-09T18:15:58Z |
| publishDate | 2019-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-b33be7c69f554cc291104e8c2d841b752023-04-13T04:36:19ZengWileyCancer Medicine2045-76342019-08-018104732474210.1002/cam4.2368Effects of somatic alterations at pathway level are more mechanism‐explanatory and clinically applicable to quantity of liver metastases of colorectal cancerZhong‐guo Zhang0Fei Ma1Shuang Zhao2Xiaoyu Yang3Fang Liu4Chenghai Xue5Liren Liu6Jin Gu7Haozhe Piao8Large‐scale Data Analysis Center of Cancer Precision Medicine Cancer Hospital of Chinese Medical University, Liaoning Provincial Cancer Institute and Hospital Shenyang ChinaWankangyuan Tianjin Gene Technology, Inc Tianjin ChinaWankangyuan Tianjin Gene Technology, Inc Tianjin ChinaLarge‐scale Data Analysis Center of Cancer Precision Medicine Cancer Hospital of Chinese Medical University, Liaoning Provincial Cancer Institute and Hospital Shenyang ChinaLarge‐scale Data Analysis Center of Cancer Precision Medicine Cancer Hospital of Chinese Medical University, Liaoning Provincial Cancer Institute and Hospital Shenyang ChinaLarge‐scale Data Analysis Center of Cancer Precision Medicine Cancer Hospital of Chinese Medical University, Liaoning Provincial Cancer Institute and Hospital Shenyang ChinaDepartment of Gastrointestinal Cancer Biology National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospitasl Tianjin ChinaMOE Key Laboratory of Bioinformatics, Beijing National Research Center for Information Science and Technology, Department of Automation Tsinghua University Beijing ChinaLarge‐scale Data Analysis Center of Cancer Precision Medicine Cancer Hospital of Chinese Medical University, Liaoning Provincial Cancer Institute and Hospital Shenyang ChinaAbstract Background The quantity of metastases lesions is an important reference when it comes to making a more informed treatment decision for patients with colorectal cancer liver metastases. However, the molecular alterations in patients with different numbers of lesions have not been systematically studied. Methods We investigated somatic alterations and microsatellite instability (MSI) of liver metastases from patients with single, multiple or diffuse metastasis lesions. A new algorithm “Pathway Damage Score” was developed to comprehensively assess the functional impact of somatic alterations at the pathway level. Pathogenic pathways of different metastasis were identified and their prognosis effects were evaluated. Furthermore, the subnetworks and affected phenotypes of the altered genes in each pathogenic pathway were analyzed. Results Somatic alterations and altered genes occurred sporadically as well as in MSI state in different metastasis types, although MSS patients had more metastatic lesions than that of the MSI patients. Every metastasis group has their own pathogenic pathways and damaged “Cargo recognition for clathrin‐mediated endocytosis” is significantly associated with poor prognosis (P < 0.001). Further pathway subnetwork analysis showed that except conventional drivers, other genes could also contribute to metastasis formation. Conclusions Progression of liver metastasis could be driven by the coefficient of all altered genes belonging to the pathways. Thus, compared to somatic alterations and genes, pathway level analysis is more reasonable for functional interpretations of molecular alterations in clinical samples.https://doi.org/10.1002/cam4.2368algorithmcancer pathwaysliver metastases lesionssomatic alterationssurvival |
| spellingShingle | Zhong‐guo Zhang Fei Ma Shuang Zhao Xiaoyu Yang Fang Liu Chenghai Xue Liren Liu Jin Gu Haozhe Piao Effects of somatic alterations at pathway level are more mechanism‐explanatory and clinically applicable to quantity of liver metastases of colorectal cancer Cancer Medicine algorithm cancer pathways liver metastases lesions somatic alterations survival |
| title | Effects of somatic alterations at pathway level are more mechanism‐explanatory and clinically applicable to quantity of liver metastases of colorectal cancer |
| title_full | Effects of somatic alterations at pathway level are more mechanism‐explanatory and clinically applicable to quantity of liver metastases of colorectal cancer |
| title_fullStr | Effects of somatic alterations at pathway level are more mechanism‐explanatory and clinically applicable to quantity of liver metastases of colorectal cancer |
| title_full_unstemmed | Effects of somatic alterations at pathway level are more mechanism‐explanatory and clinically applicable to quantity of liver metastases of colorectal cancer |
| title_short | Effects of somatic alterations at pathway level are more mechanism‐explanatory and clinically applicable to quantity of liver metastases of colorectal cancer |
| title_sort | effects of somatic alterations at pathway level are more mechanism explanatory and clinically applicable to quantity of liver metastases of colorectal cancer |
| topic | algorithm cancer pathways liver metastases lesions somatic alterations survival |
| url | https://doi.org/10.1002/cam4.2368 |
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