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Association of KRAS mutation with tumor deposit status and overall survival of colorectal cancer

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Abstract

Purpose

To examine associations of KRAS mutation with tumor deposit status and overall survival in colorectal cancer (CRC) patients.

Methods

This retrospective cohort study included patients with incidental CRC diagnosed during 2010–2014 and recorded statuses of KRAS and tumor deposit in the National Cancer Database of the USA. Multivariable logistic regression and time-varying Cox regression analyses were used.

Results

We included 45,761 CRC patients with KRAS status (24,027 [52.5%] men, 24,240 [53.0%] < 65 years old, 17,338 [37.9%] with KRAS mutation). Adjusted for microsatellite instability, age, pathologic stage and tumor grade, KRAS mutation (versus wild type) was associated with tumor deposit presence (odds ratio = 1.11, 95% CI 1.02–1.20). KRAS mutation was also linked to worse overall survival of CRC patients regardless of tumor deposit status (adjusted Hazard ratio [HR] = 1.20, 95% CI 1.07–1.33 for CRC with tumor deposits, and adjusted HR = 1.24, 95% CI 1.14–1.35 or CRC without) or tumor stage (adjusted HR = 1.32, 95% CI 1.14–1.54 for early-stage and adjusted HR = 1.18, 95% CI 1.10–1.27 for late-stage). Microsatellite instability was associated with better overall survival in CRC without tumor deposit (adjusted HR = 0.89, 95% CI 0.79–0.99), but not in CRC with tumor deposit (adjusted HR = 1.12, 95% CI 0.97–1.30).

Conclusion

KRAS mutation is independently associated with tumor deposit presence and a worse overall survival in CRC patients.

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Acknowledgments

The study was in part supported by an Initiative for Multidisciplinary Research Teams (IMRT) award from Rutgers University, Newark, NJ (to N.G. and L.Z.), the U.S. National Institute of Health (R01 AT010243 to N.G.), the National Natural Science Foundation of China (No. 81872387 to M.Z.) and China Scholarship Council (to M.Z.). The funders have no roles in the study design or manuscript preparation.

Author information

Authors and Affiliations

  1. Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, China

    Meifang Zhang & Jing-Ping Yun

  2. Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA

    Meifang Zhang, Wenwei Hu, Yong Lin, Zhaohui Feng & Lanjing Zhang

  3. Department of Pathology, Princeton Medical Center, 1 Plainsboro Rd, Plainsboro, NJ, 08536, USA

    Meifang Zhang & Lanjing Zhang

  4. Department of Pathology, University at Buffalo, Buffalo, NY, USA

    Kun Hu

  5. Department of Biostatistics, School of Public Health, Rutgers University, Piscataway, NJ, USA

    Yong Lin

  6. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China

    Jing-Ping Yun

  7. Department of Biological Sciences, Rutgers University, Newark, NJ, USA

    Nan Gao & Lanjing Zhang

  8. Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA

    Lanjing Zhang

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  1. Meifang Zhang
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Contributions

MZ, NG, JY, and LZ designed the study, LZ extracted the data, MZ, WH, and LZ analyzed the data, MZ and LZ wrote the first draft of the manuscript. The final draft has been edited and approved by all authors.

Corresponding author

Correspondence to Lanjing Zhang.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

We cannot share the patient-level data which are confidential and were obtained with review and approval from the National Cancer Database and the American College of Surgeons.

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The work has been deposited to medRxiv as a preprint, with citation of medRxiv 19003210; https://doi.org/10.1101/19003210.

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Zhang, M., Hu, W., Hu, K. et al. Association of KRAS mutation with tumor deposit status and overall survival of colorectal cancer. Cancer Causes Control 31, 683–689 (2020). https://doi.org/10.1007/s10552-020-01313-0

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  • DOI: https://doi.org/10.1007/s10552-020-01313-0

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