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Published on: March 14, 2019
Mutations in epidermal growth factor receptor and K-ras in Chinese patients with colorectal cancer
Zuo Yunxia1, Cao Jun, Zhu Guanshan
1Department of Medical Oncology, Fudan University Cancer Hospital, Shanghai Medical School, Shanghai 200032, PR China.
Background:
Mutations of EGFR and K-ras are biomarkers for predicting the efficacy of targeting agents in non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). Data on the gene mutation status of EGFR and K-ras in Chinese patients with CRC are limited.
Methods:
EGFR mutations in exon 18-21 and K-ras mutations in exon 1 and 2 were detected in tumor samples from 101 Chinese patients with CRC by polymerase chain reaction and Sanger sequencing. [corrected] The relationship between patients' characteristics and survival time and gene mutation status were analyzed using the Statistical Package for the Social Sciences.
Results:
Only two samples (2.0%) had EGFR mutations in exon 18 or 21, and 33 of 101 samples (32.7%) had K-ras mutations in codon 12, 13, 45, 69, or 80. Univariate analysis suggested that differentiation might be correlated with K-ras mutations (p = 0.05), which was confirmed by a logistic regression model (p = 0.04). The median overall survival (OS) and median survival after metastasis were 44.0 and 18.0 months, respectively, in the mutant K-ras group, and 53.3 and 19.0 months, respectively, in the wild K-ras group. K-ras mutation was not an independent prognostic factor for OS or survival after metastasis (p = 0.79 and 0.78, respectively).
Conclusions:
In Chinese patients with CRC, EGFR mutations were rare, and K-ras mutations were similar to those of Europeans. New mutations in codons 45, 69, and 80 were found in the Chinese population. Poor differentiation was an independent factor related to K-ras mutations.
Insights
EGFR mutations are rare in Chinese colorectal cancer (CRC) patients, while K-ras mutations are common and linked to poor differentiation. K-ras mutations did not independently affect survival in this cohort.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Epidermal Growth Factor Receptor (EGFR) and Kirsten Rat Sarcoma (K-ras) mutations are key biomarkers for targeted therapies in non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC).
- Limited data exists on the prevalence and clinical significance of EGFR and K-ras gene mutations in Chinese patients diagnosed with CRC.
Purpose of the Study:
- To investigate the mutation status of EGFR and K-ras genes in a cohort of Chinese CRC patients.
- To analyze the correlation between gene mutation status, patient characteristics, and survival outcomes.
Main Methods:
- Tumor samples from 101 Chinese CRC patients were analyzed for EGFR mutations (exons 18-21) and K-ras mutations (exons 1-2) using polymerase chain reaction and Sanger sequencing.
- Statistical analysis, including logistic regression, was employed to assess relationships between mutations, patient demographics, and survival.
Main Results:
- EGFR mutations were infrequent (2.0%), while K-ras mutations were detected in 32.7% of patients, with novel mutations identified in codons 45, 69, and 80.
- Poor differentiation was significantly associated with K-ras mutations (p=0.04).
- K-ras mutation status did not emerge as an independent prognostic factor for overall survival or post-metastasis survival.
Conclusions:
- EGFR mutations are rare in Chinese CRC patients, whereas K-ras mutation frequencies are comparable to European populations.
- The study identified novel K-ras mutations in codons 45, 69, and 80 within the Chinese population.
- Poor tumor differentiation is an independent factor associated with K-ras mutations in this CRC cohort.
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