Panomics reveals patient individuality as the major driver of colorectal cancer progression

Friederike Praus; Axel Künstner; Thorben Sauer; Michael Kohl; Katharina Kern; Steffen Deichmann; Ákos Végvári; Tobias Keck; Hauke Busch; Jens K. Habermann; Timo Gemoll

doi:10.1186/s12967-022-03855-0

Panomics reveals patient individuality as the major driver of colorectal cancer progression

Friederike Praus, Axel Künstner, Thorben Sauer, Michael Kohl, Katharina Kern, Steffen Deichmann, Ákos Végvári, Tobias Keck, Hauke Busch, Jens K. Habermann, Timo Gemoll^*

^*Corresponding author for this work

Karolinska Institutet

6 Citations (Scopus)

Abstract

Background: Colorectal cancer (CRC) is one of the most prevalent cancers, with over one million new cases per year. Overall, prognosis of CRC largely depends on the disease stage and metastatic status. As precision oncology for patients with CRC continues to improve, this study aimed to integrate genomic, transcriptomic, and proteomic analyses to identify significant differences in expression during CRC progression using a unique set of paired patient samples while considering tumour heterogeneity. Methods: We analysed fresh-frozen tissue samples prepared under strict cryogenic conditions of matched healthy colon mucosa, colorectal carcinoma, and liver metastasis from the same patients. Somatic mutations of known cancer-related genes were analysed using Illumina's TruSeq Amplicon Cancer Panel; the transcriptome was assessed comprehensively using Clariom D microarrays. The global proteome was evaluated by liquid chromatography-coupled mass spectrometry (LC‒MS/MS) and validated by two-dimensional difference in-gel electrophoresis. Subsequent unsupervised principal component clustering, statistical comparisons, and gene set enrichment analyses were calculated based on differential expression results. Results: Although panomics revealed low RNA and protein expression of CA1, CLCA1, MATN2, AHCYL2, and FCGBP in malignant tissues compared to healthy colon mucosa, no differentially expressed RNA or protein targets were detected between tumour and metastatic tissues. Subsequent intra-patient comparisons revealed highly specific expression differences (e.g., SRSF3, OLFM4, and CEACAM5) associated with patient-specific transcriptomes and proteomes. Conclusion: Our research results highlight the importance of inter- and intra-tumour heterogeneity as well as individual, patient-paired evaluations for clinical studies. In addition to changes among groups reflecting CRC progression, we identified significant expression differences between normal colon mucosa, primary tumour, and liver metastasis samples from individuals, which might accelerate implementation of precision oncology in the future.

Original language	English
Article number	41
Journal	Journal of Translational Medicine
Volume	21
Issue number	1
Pages (from-to)	41
DOIs	https://doi.org/10.1186/s12967-022-03855-0
Publication status	Published - 23.01.2023

Funding

Grants from the Ad Infinitum Foundation and Werner & Clara Kreitz are gratefully acknowledged. This study was performed in collaboration with the Surgical Center for Translational Oncology-Lübeck (SCTO-L), the Lübeck Integrated Oncology Network (LION), and the Interdisciplinary Center for Biobanking-Lübeck (ICB-L). The authors would like to thank Katja Klempt-Giessing, Julia Horn, Emma Neumann, and Gisela Grosser-Pape for excellent technical assistance. This manuscript has been released as a preprint at medRxiv (ID: MEDRXIV/2022/280355, [64]). Open Access funding enabled and organized by Projekt DEAL. Thorben Sauer received a scholarship from the Ad Infinitum Foundation. Hauke Busch acknowledges funding by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany`s Excellence Strategy (EXC 22167-390884018). This work is further supported by the Regional Economic Programme Funded by the European Union, the Federal Government, and Land Schleswig–Holstein (LPW-E/1.2.2/1888). Grants from the Ad Infinitum Foundation and Werner & Clara Kreitz are gratefully acknowledged. This study was performed in collaboration with the Surgical Center for Translational Oncology-Lübeck (SCTO-L), the Lübeck Integrated Oncology Network (LION), and the Interdisciplinary Center for Biobanking-Lübeck (ICB-L). The authors would like to thank Katja Klempt-Giessing, Julia Horn, Emma Neumann, and Gisela Grosser-Pape for excellent technical assistance. This manuscript has been released as a preprint at medRxiv (ID: MEDRXIV/2022/280355, []).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Research Area: Luebeck Integrated Oncology Network (LION)
Centers: University Cancer Center Schleswig-Holstein (UCCSH)

DFG Research Classification Scheme

2.22-14 Hematology, Oncology

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10.1186/s12967-022-03855-0

Cite this

@article{273475045a844689b57d99e8568b721c,

title = "Panomics reveals patient individuality as the major driver of colorectal cancer progression",

abstract = "Background: Colorectal cancer (CRC) is one of the most prevalent cancers, with over one million new cases per year. Overall, prognosis of CRC largely depends on the disease stage and metastatic status. As precision oncology for patients with CRC continues to improve, this study aimed to integrate genomic, transcriptomic, and proteomic analyses to identify significant differences in expression during CRC progression using a unique set of paired patient samples while considering tumour heterogeneity. Methods: We analysed fresh-frozen tissue samples prepared under strict cryogenic conditions of matched healthy colon mucosa, colorectal carcinoma, and liver metastasis from the same patients. Somatic mutations of known cancer-related genes were analysed using Illumina's TruSeq Amplicon Cancer Panel; the transcriptome was assessed comprehensively using Clariom D microarrays. The global proteome was evaluated by liquid chromatography-coupled mass spectrometry (LC‒MS/MS) and validated by two-dimensional difference in-gel electrophoresis. Subsequent unsupervised principal component clustering, statistical comparisons, and gene set enrichment analyses were calculated based on differential expression results. Results: Although panomics revealed low RNA and protein expression of CA1, CLCA1, MATN2, AHCYL2, and FCGBP in malignant tissues compared to healthy colon mucosa, no differentially expressed RNA or protein targets were detected between tumour and metastatic tissues. Subsequent intra-patient comparisons revealed highly specific expression differences (e.g., SRSF3, OLFM4, and CEACAM5) associated with patient-specific transcriptomes and proteomes. Conclusion: Our research results highlight the importance of inter- and intra-tumour heterogeneity as well as individual, patient-paired evaluations for clinical studies. In addition to changes among groups reflecting CRC progression, we identified significant expression differences between normal colon mucosa, primary tumour, and liver metastasis samples from individuals, which might accelerate implementation of precision oncology in the future.",

author = "Friederike Praus and Axel K{\"u}nstner and Thorben Sauer and Michael Kohl and Katharina Kern and Steffen Deichmann and {\'A}kos V{\'e}gv{\'a}ri and Tobias Keck and Hauke Busch and Habermann, \{Jens K.\} and Timo Gemoll",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s). {\textcopyright} 2023. The Author(s).",

year = "2023",

month = jan,

day = "23",

doi = "10.1186/s12967-022-03855-0",

language = "English",

volume = "21",

pages = "41",

journal = "Journal of Translational Medicine",

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TY - JOUR

T1 - Panomics reveals patient individuality as the major driver of colorectal cancer progression

AU - Praus, Friederike

AU - Künstner, Axel

AU - Sauer, Thorben

AU - Kohl, Michael

AU - Kern, Katharina

AU - Deichmann, Steffen

AU - Végvári, Ákos

AU - Keck, Tobias

AU - Busch, Hauke

AU - Habermann, Jens K.

AU - Gemoll, Timo

PY - 2023/1/23

Y1 - 2023/1/23

N2 - Background: Colorectal cancer (CRC) is one of the most prevalent cancers, with over one million new cases per year. Overall, prognosis of CRC largely depends on the disease stage and metastatic status. As precision oncology for patients with CRC continues to improve, this study aimed to integrate genomic, transcriptomic, and proteomic analyses to identify significant differences in expression during CRC progression using a unique set of paired patient samples while considering tumour heterogeneity. Methods: We analysed fresh-frozen tissue samples prepared under strict cryogenic conditions of matched healthy colon mucosa, colorectal carcinoma, and liver metastasis from the same patients. Somatic mutations of known cancer-related genes were analysed using Illumina's TruSeq Amplicon Cancer Panel; the transcriptome was assessed comprehensively using Clariom D microarrays. The global proteome was evaluated by liquid chromatography-coupled mass spectrometry (LC‒MS/MS) and validated by two-dimensional difference in-gel electrophoresis. Subsequent unsupervised principal component clustering, statistical comparisons, and gene set enrichment analyses were calculated based on differential expression results. Results: Although panomics revealed low RNA and protein expression of CA1, CLCA1, MATN2, AHCYL2, and FCGBP in malignant tissues compared to healthy colon mucosa, no differentially expressed RNA or protein targets were detected between tumour and metastatic tissues. Subsequent intra-patient comparisons revealed highly specific expression differences (e.g., SRSF3, OLFM4, and CEACAM5) associated with patient-specific transcriptomes and proteomes. Conclusion: Our research results highlight the importance of inter- and intra-tumour heterogeneity as well as individual, patient-paired evaluations for clinical studies. In addition to changes among groups reflecting CRC progression, we identified significant expression differences between normal colon mucosa, primary tumour, and liver metastasis samples from individuals, which might accelerate implementation of precision oncology in the future.

AB - Background: Colorectal cancer (CRC) is one of the most prevalent cancers, with over one million new cases per year. Overall, prognosis of CRC largely depends on the disease stage and metastatic status. As precision oncology for patients with CRC continues to improve, this study aimed to integrate genomic, transcriptomic, and proteomic analyses to identify significant differences in expression during CRC progression using a unique set of paired patient samples while considering tumour heterogeneity. Methods: We analysed fresh-frozen tissue samples prepared under strict cryogenic conditions of matched healthy colon mucosa, colorectal carcinoma, and liver metastasis from the same patients. Somatic mutations of known cancer-related genes were analysed using Illumina's TruSeq Amplicon Cancer Panel; the transcriptome was assessed comprehensively using Clariom D microarrays. The global proteome was evaluated by liquid chromatography-coupled mass spectrometry (LC‒MS/MS) and validated by two-dimensional difference in-gel electrophoresis. Subsequent unsupervised principal component clustering, statistical comparisons, and gene set enrichment analyses were calculated based on differential expression results. Results: Although panomics revealed low RNA and protein expression of CA1, CLCA1, MATN2, AHCYL2, and FCGBP in malignant tissues compared to healthy colon mucosa, no differentially expressed RNA or protein targets were detected between tumour and metastatic tissues. Subsequent intra-patient comparisons revealed highly specific expression differences (e.g., SRSF3, OLFM4, and CEACAM5) associated with patient-specific transcriptomes and proteomes. Conclusion: Our research results highlight the importance of inter- and intra-tumour heterogeneity as well as individual, patient-paired evaluations for clinical studies. In addition to changes among groups reflecting CRC progression, we identified significant expression differences between normal colon mucosa, primary tumour, and liver metastasis samples from individuals, which might accelerate implementation of precision oncology in the future.

UR - https://www.scopus.com/pages/publications/85146762028

U2 - 10.1186/s12967-022-03855-0

DO - 10.1186/s12967-022-03855-0

M3 - Journal articles

C2 - 36691026

AN - SCOPUS:85146762028

SN - 1479-5876

VL - 21

SP - 41

JO - Journal of Translational Medicine

JF - Journal of Translational Medicine

IS - 1

M1 - 41

ER -

Panomics reveals patient individuality as the major driver of colorectal cancer progression

Abstract

Funding

UN SDGs

Research Areas and Centers

DFG Research Classification Scheme

Access to Document

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