Prognosis prediction of stage IV colorectal cancer patients by mRNA transcriptional profile
Abstract Background Stage IV colorectal cancer patients with liver metastasis represent a special group of CRC patients with poor prognosis. The prognostic factors have not been investigated for stage IV CRC patients undergoing primary cancer resection but not candidates for metastasis resection. Me...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-12-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.4824 |
| _version_ | 1811291439485681664 |
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| author | Bian Wu Jinwei Yang Zhiwei Qin Hongping Yang Jingyi Shao Yun Shang |
| author_facet | Bian Wu Jinwei Yang Zhiwei Qin Hongping Yang Jingyi Shao Yun Shang |
| author_sort | Bian Wu |
| collection | DOAJ |
| description | Abstract Background Stage IV colorectal cancer patients with liver metastasis represent a special group of CRC patients with poor prognosis. The prognostic factors have not been investigated for stage IV CRC patients undergoing primary cancer resection but not candidates for metastasis resection. Methods Ninety‐nine stage IV CRC patients who underwent primary cancer resection without metastasis resection were retrospectively recruited. Both whole‐exome sequencing (WES) and RNA‐seq were performed with frozen primary cancer tissues, using para‐cancerous normal tissues as the control. Valid data were obtained from 78 patients for WES and 84 patients for RNA‐seq. Univariate, multivariate Cox analyses were performed and Nomogram model was established to predict patient prognosis. Results The correlation between patient prognosis and clinicopathological factors, mutational status, or mRNA level changes was examined. Univariate (p = 0.0007) and subsequent multivariate analyses on clinicopathological factors showed that location (left or right) was the only independent risk factor for patient prognosis (HR = 3.63; 95% CI: 1.56–8.40, p = 0.003), while T, N, M staging, gender, race, location (rectum or colon), and pathological types were not stratifying factors. The mutational status of APC, TP53, KRAS, TTN, SYNE1, SMAD4, PIK3CA, RYR2, and BRAF did not show significant stratification in patient prognosis. RNA‐seq showed that genes related to membrane function, ion channels, transporters, or receptors were among those with significant mRNA level alterations. Univariate analysis identified 97 genes with significantly altered mRNA levels, while NEUROD1, FGF18, SFTA2, PLAC1, SAA2, DSCAML1, and OTOP3 were significant in multivariate analysis. A risk model was established to stratify the prognosis of stage IV CRC patients. A Nomogram model was established with these genes to predict individual patient prognosis. Conclusions A panel of eight genes with significant mRNA level alterations was capable of predicting the prognosis and risk of the specific patient group. Future prospective study is needed to validate the model. |
| first_indexed | 2024-04-13T04:29:24Z |
| format | Article |
| id | doaj.art-3a46787ea6c946f981af2aecf0a5c582 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-13T04:29:24Z |
| publishDate | 2022-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-3a46787ea6c946f981af2aecf0a5c5822022-12-22T03:02:22ZengWileyCancer Medicine2045-76342022-12-0111244900491210.1002/cam4.4824Prognosis prediction of stage IV colorectal cancer patients by mRNA transcriptional profileBian Wu0Jinwei Yang1Zhiwei Qin2Hongping Yang3Jingyi Shao4Yun Shang5Department of General Surgery II the First People's Hospital of Yunnan Province Kunming Yunnan ChinaDepartment of General Surgery II the First People's Hospital of Yunnan Province Kunming Yunnan ChinaDepartment of General Surgery Wenshan people's Hospital of Yunnan Province Yunnan ChinaDepartment of Anus and Intestine Surgery Qujing Hospital of Traditional Chinese Medicine Qujing Yunnan ChinaDepartment of Reproductive Medicine the First People's Hospital of Yunnan Province Kunming Yunnan ChinaDepartment of General Surgery II the First People's Hospital of Yunnan Province Kunming Yunnan ChinaAbstract Background Stage IV colorectal cancer patients with liver metastasis represent a special group of CRC patients with poor prognosis. The prognostic factors have not been investigated for stage IV CRC patients undergoing primary cancer resection but not candidates for metastasis resection. Methods Ninety‐nine stage IV CRC patients who underwent primary cancer resection without metastasis resection were retrospectively recruited. Both whole‐exome sequencing (WES) and RNA‐seq were performed with frozen primary cancer tissues, using para‐cancerous normal tissues as the control. Valid data were obtained from 78 patients for WES and 84 patients for RNA‐seq. Univariate, multivariate Cox analyses were performed and Nomogram model was established to predict patient prognosis. Results The correlation between patient prognosis and clinicopathological factors, mutational status, or mRNA level changes was examined. Univariate (p = 0.0007) and subsequent multivariate analyses on clinicopathological factors showed that location (left or right) was the only independent risk factor for patient prognosis (HR = 3.63; 95% CI: 1.56–8.40, p = 0.003), while T, N, M staging, gender, race, location (rectum or colon), and pathological types were not stratifying factors. The mutational status of APC, TP53, KRAS, TTN, SYNE1, SMAD4, PIK3CA, RYR2, and BRAF did not show significant stratification in patient prognosis. RNA‐seq showed that genes related to membrane function, ion channels, transporters, or receptors were among those with significant mRNA level alterations. Univariate analysis identified 97 genes with significantly altered mRNA levels, while NEUROD1, FGF18, SFTA2, PLAC1, SAA2, DSCAML1, and OTOP3 were significant in multivariate analysis. A risk model was established to stratify the prognosis of stage IV CRC patients. A Nomogram model was established with these genes to predict individual patient prognosis. Conclusions A panel of eight genes with significant mRNA level alterations was capable of predicting the prognosis and risk of the specific patient group. Future prospective study is needed to validate the model.https://doi.org/10.1002/cam4.4824colorectal cancerexpressionmutationprognosisRNA‐seqtranscription |
| spellingShingle | Bian Wu Jinwei Yang Zhiwei Qin Hongping Yang Jingyi Shao Yun Shang Prognosis prediction of stage IV colorectal cancer patients by mRNA transcriptional profile Cancer Medicine colorectal cancer expression mutation prognosis RNA‐seq transcription |
| title | Prognosis prediction of stage IV colorectal cancer patients by mRNA transcriptional profile |
| title_full | Prognosis prediction of stage IV colorectal cancer patients by mRNA transcriptional profile |
| title_fullStr | Prognosis prediction of stage IV colorectal cancer patients by mRNA transcriptional profile |
| title_full_unstemmed | Prognosis prediction of stage IV colorectal cancer patients by mRNA transcriptional profile |
| title_short | Prognosis prediction of stage IV colorectal cancer patients by mRNA transcriptional profile |
| title_sort | prognosis prediction of stage iv colorectal cancer patients by mrna transcriptional profile |
| topic | colorectal cancer expression mutation prognosis RNA‐seq transcription |
| url | https://doi.org/10.1002/cam4.4824 |
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