Single-cell genomic profile-based analysis of tissue differentiation in colorectal cancer
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ngle-cell genomic profile-based analysis of tissue differentiation in colorectal cancer 1*
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Hao Jiang , Hongquan Zhang & Xuegong Zhang 1
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MOE Key Lab of Bioinformatics and Bioinformatics Division, BNRIST; Department of Automation; Tsinghua-Peking Joint Center for Life
Sciences; Center for Synthetic and Systems Biology, Tsinghua University, Beijing 100084, China; MOE Key Laboratory of Carcinogenesis and Translational Research; Department of Human Anatomy, Histology and Embryology; State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China Received July 31, 2020; accepted September 19, 2020; published online October 30, 2020
Colorectal cancer (CRC) progression is associated with cancer cell dedifferentiation and stemness acquisition. Several methods have been developed to identify stemness signatures in CRCs. However, studies that directly measured the degree of dedifferentiation in CRC tissues are limited. It is unclear how the differentiation states change during CRC progression. To address this, we develop a method to analyze the tissue differentiation spectrum in colorectal cancer using normal gastrointestinal singlecell transcriptome data. Applying this method on 281 tumor samples from The Cancer Genome Atlas Colon Adenocarcinoma dataset, we identified three major CRC subtypes with distinct tissue differentiation pattern. We observed that differentiation states are closely correlated with anti-tumor immune response and patient outcomes in CRC. Highly dedifferentiated CRC samples escaped the immune surveillance and exhibited poor outcomes; mildly dedifferentiated CRC samples showed resistance to anti-tumor immune responses and had a worse survival rate; well-differentiated CRC samples showed sustained anti-tumor immune responses and had a good prognosis. Overall, the spectrum of tissue differentiation observed in CRCs can be used for future clinical risk stratification and subtype-based therapy selection. colorectal cancer, single-cell, prognosis, differentiation degree, caner stemness, immune response, immune cell infiltration Citation:
Jiang, H., Zhang, H., and Zhang, X. (2020). Single-cell genomic profile-based analysis of tissue differentiation in colorectal cancer. Sci China Life Sci 63, https://doi.org/10.1007/s11427-020-1811-5
INTRODUCTION Colorectal cancer (CRC) is the fourth most deadly cancer globally (Dekker et al., 2019). During cancer progression, the loss of differentiation and gain of progenitor-like or stemlike properties give rise to self-renewing cancer cells, which is related to therapy resistance and tumor metastasis. Low degree of differentiation state and high level of stemness signature lead to poor prognosis in CRC patients (Friedmann-Morvinski and Verma, 2014; Saygin et al., 2019; Shimokawa et al., 2017; Zeuner et al., 2014). Understanding *Corresponding author (email: [email protected])
the stemness state and differentiation degree in CRCs gives opportunities for improvement of patient outcomes through improved
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