Exploring biomarkers for prognosis and neoadjuvant chemosensitivity in rectal cancer: Multi-omics and ctDNA sequencing collaboration
IntroductionThis study aimed to identified the key genes and sequencing metrics for predicting prognosis and efficacy of neoadjuvant chemotherapy (nCT) in rectal cancer (RC) based on genomic DNA sequencing in samples with different origin and multi-omics association database.MethodsWe collected 16 R...
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| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1013828/full |
| _version_ | 1811178434582282240 |
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| author | Xiu-Feng Jiang Bo-Miao Zhang Fen-Qi Du Jun-Nan Guo Dan Wang Yi-En Li Shen-Hui Deng Bin-Bin Cui Yan-Long Liu |
| author_facet | Xiu-Feng Jiang Bo-Miao Zhang Fen-Qi Du Jun-Nan Guo Dan Wang Yi-En Li Shen-Hui Deng Bin-Bin Cui Yan-Long Liu |
| author_sort | Xiu-Feng Jiang |
| collection | DOAJ |
| description | IntroductionThis study aimed to identified the key genes and sequencing metrics for predicting prognosis and efficacy of neoadjuvant chemotherapy (nCT) in rectal cancer (RC) based on genomic DNA sequencing in samples with different origin and multi-omics association database.MethodsWe collected 16 RC patients and obtained DNA sequencing data from cancer tissues and plasma cell-free DNA before and after nCT. Various gene variations were analyzed, including single nucleotide variants (SNV), copy number variation (CNV), tumor mutation burden (TMB), copy number instability (CNI) and mutant-allele tumor heterogeneity (MATH). We also identified genes by which CNV level can differentiate the response to nCT. The Cancer Genome Atlas database and the Clinical Proteomic Tumor Analysis Consortium database were used to further evaluate the specific role of therapeutic relevant genes and screen out the key genes in multi-omics levels. After the intersection of the screened genes from differential expression analysis, survival analysis and principal components analysis dimensionality reduction cluster analysis, the key genes were finally identified.ResultsThe genes CNV level of principal component genes in baseline blood and cancer tissues could significantly distinguish the two groups of patients. The CNV of HSP90AA1, EGFR, SRC, MTOR, etc. were relatively gained in the better group compared with the poor group in baseline blood. The CNI and TMB was significantly different between the two groups. The increased expression of HSP90AA1, EGFR, and SRC was associated with increased sensitivity to multiple chemotherapeutic drugs. The nCT predictive score obtained by therapeutic relevant genes could be a potential prognostic indicator, and the combination with TMB could further refine prognostic prediction for patients. After a series of analysis in multi-omics association database, EGFR and HSP90AA1 with significant differences in multiple aspects were identified as the key predictive genes related to prognosis and the sensitivity of nCT.DiscussionThis work revealed that effective combined application and analysis in multi-omics data are critical to search for predictive biomarkers. The key genes EGFR and HSP90AA1 could serve as an effective biomarker to predict prognose and neoadjuvant chemosensitivity. |
| first_indexed | 2024-04-11T06:18:16Z |
| format | Article |
| id | doaj.art-3628f5dbda08440099711464f1cbc504 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T06:18:16Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-3628f5dbda08440099711464f1cbc5042022-12-22T04:40:58ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-12-011310.3389/fimmu.2022.10138281013828Exploring biomarkers for prognosis and neoadjuvant chemosensitivity in rectal cancer: Multi-omics and ctDNA sequencing collaborationXiu-Feng Jiang0Bo-Miao Zhang1Fen-Qi Du2Jun-Nan Guo3Dan Wang4Yi-En Li5Shen-Hui Deng6Bin-Bin Cui7Yan-Long Liu8Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Neurology, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, ChinaDepartment of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Anesthesiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, ChinaIntroductionThis study aimed to identified the key genes and sequencing metrics for predicting prognosis and efficacy of neoadjuvant chemotherapy (nCT) in rectal cancer (RC) based on genomic DNA sequencing in samples with different origin and multi-omics association database.MethodsWe collected 16 RC patients and obtained DNA sequencing data from cancer tissues and plasma cell-free DNA before and after nCT. Various gene variations were analyzed, including single nucleotide variants (SNV), copy number variation (CNV), tumor mutation burden (TMB), copy number instability (CNI) and mutant-allele tumor heterogeneity (MATH). We also identified genes by which CNV level can differentiate the response to nCT. The Cancer Genome Atlas database and the Clinical Proteomic Tumor Analysis Consortium database were used to further evaluate the specific role of therapeutic relevant genes and screen out the key genes in multi-omics levels. After the intersection of the screened genes from differential expression analysis, survival analysis and principal components analysis dimensionality reduction cluster analysis, the key genes were finally identified.ResultsThe genes CNV level of principal component genes in baseline blood and cancer tissues could significantly distinguish the two groups of patients. The CNV of HSP90AA1, EGFR, SRC, MTOR, etc. were relatively gained in the better group compared with the poor group in baseline blood. The CNI and TMB was significantly different between the two groups. The increased expression of HSP90AA1, EGFR, and SRC was associated with increased sensitivity to multiple chemotherapeutic drugs. The nCT predictive score obtained by therapeutic relevant genes could be a potential prognostic indicator, and the combination with TMB could further refine prognostic prediction for patients. After a series of analysis in multi-omics association database, EGFR and HSP90AA1 with significant differences in multiple aspects were identified as the key predictive genes related to prognosis and the sensitivity of nCT.DiscussionThis work revealed that effective combined application and analysis in multi-omics data are critical to search for predictive biomarkers. The key genes EGFR and HSP90AA1 could serve as an effective biomarker to predict prognose and neoadjuvant chemosensitivity.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1013828/fullrectal cancercell-free DNAgenomic sequencingmulti-omicsprognosisneoadjuvant chemotherapy |
| spellingShingle | Xiu-Feng Jiang Bo-Miao Zhang Fen-Qi Du Jun-Nan Guo Dan Wang Yi-En Li Shen-Hui Deng Bin-Bin Cui Yan-Long Liu Exploring biomarkers for prognosis and neoadjuvant chemosensitivity in rectal cancer: Multi-omics and ctDNA sequencing collaboration Frontiers in Immunology rectal cancer cell-free DNA genomic sequencing multi-omics prognosis neoadjuvant chemotherapy |
| title | Exploring biomarkers for prognosis and neoadjuvant chemosensitivity in rectal cancer: Multi-omics and ctDNA sequencing collaboration |
| title_full | Exploring biomarkers for prognosis and neoadjuvant chemosensitivity in rectal cancer: Multi-omics and ctDNA sequencing collaboration |
| title_fullStr | Exploring biomarkers for prognosis and neoadjuvant chemosensitivity in rectal cancer: Multi-omics and ctDNA sequencing collaboration |
| title_full_unstemmed | Exploring biomarkers for prognosis and neoadjuvant chemosensitivity in rectal cancer: Multi-omics and ctDNA sequencing collaboration |
| title_short | Exploring biomarkers for prognosis and neoadjuvant chemosensitivity in rectal cancer: Multi-omics and ctDNA sequencing collaboration |
| title_sort | exploring biomarkers for prognosis and neoadjuvant chemosensitivity in rectal cancer multi omics and ctdna sequencing collaboration |
| topic | rectal cancer cell-free DNA genomic sequencing multi-omics prognosis neoadjuvant chemotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1013828/full |
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