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KRAS Mutation and NF-κB Activation Indicates Tolerance of Chemotherapy and Poor Prognosis in Colorectal Cancer

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Abstract

Background

Evidence shows a strong relationship between KRAS mutations and the NF-κB signaling pathway. In colorectal cancer, however, the study of this subject has been very limited and results are inconsistent.

Aims

To examine the relationship between KRAS mutations and NF-κB activation and their effect on chemotherapy response and survival of colorectal cancer patients.

Materials and Methods

NF-κB activation was analyzed by immunohistochemistry in 167 primary colorectal cancer specimens in which the KRAS mutation status was confirmed. Clinical and pathologic data were extracted from the medical records and reviewed.

Results

Of 167 tumors screened, 63 (37.7 %) had NF-κB activation, 59 (35.3 %) had KRAS mutations, and 30 (18.0 %) had both NF-κB activation and KRAS mutations. The frequency of NF-κB activation in tumors with KRAS mutations was significantly higher than in tumors with wild type KRAS; 50.8 versus 30.6 %, P = 0.012. Patients with both KRAS mutations and NF-κB activation had a lower objective response to first-line chemotherapy than patients with other tumors, 23.8 versus 49.4 % (P = 0.035). Compared to patients with both KRAS mutations and NF-κB activation, overall survival of patients in other groups was significantly higher; median overall survival was 28.4 months (95 % CI 21.0–35.8) versus 46.3 months (95 % CI 39.4–53.2), hazard ratio 0.259 (95 % CI 0.125–0.538), P = 0.005.

Conclusions

NF-κB activation was associated with KRAS mutation, and both KRAS mutation and NF-κB activation were indicative of high tolerance of chemotherapy and poor prognosis for colorectal cancer patients. Tumors with KRAS mutations and NF-κB activation may be a unique subtype of colorectal cancer.

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Acknowledgments

We thank Drs Lin Chen (Department of Internal Medicine, Fujian Provincial Tumor Hospital) and Zhiwei Tang (Department of Immuno-Oncology Laboratory, Fujian Provincial Cancer Hospital) for helping with collection of the data. The project was supported by the Medical Innovation Foundation of Fujian Province (no. 2007-CXB-1).

Conflict of interest

No potential conflicts of interest were disclosed.

Author information

Authors and Affiliations

  1. Graduate School of Education, Fujian Medical University, Fuzhou, Fujian Province, 350014, People’s Republic of China

    Gen Lin

  2. Department of Medical Oncology, Fujian Provincial Cancer Hospital, Fuzhou, Fujian Province, 350014, People’s Republic of China

    Gen Lin

  3. Department of Pathology, Fujian Medical university, Fuzhou, Fujian Province, 350014, People’s Republic of China

    Xiong-wei Zheng & Chao Li

  4. Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou, Fujian Province, 350014, People’s Republic of China

    Qiang Chen & Yun-bin Ye

  5. Department of Medical Oncology, Union Hospital of Fujian Medical University, Fuzhou, Fujian Province, 350014, People’s Republic of China

    Qiang Chen

  6. Laboratory of Immuno-Oncology, Fujian Provincial Cancer Hospital, Fujian Medical university, Fuzhou, Fujian Province, 350014, People’s Republic of China

    Yun-bin Ye

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  1. Gen Lin
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  2. Xiong-wei Zheng
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Correspondence to Qiang Chen or Yun-bin Ye.

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Lin, G., Zheng, Xw., Li, C. et al. KRAS Mutation and NF-κB Activation Indicates Tolerance of Chemotherapy and Poor Prognosis in Colorectal Cancer. Dig Dis Sci 57, 2325–2333 (2012). https://doi.org/10.1007/s10620-012-2172-x

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  • DOI: https://doi.org/10.1007/s10620-012-2172-x

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