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Detection of activated KRAS from cancer patient peripheral blood using a weighted enzymatic chip array
Ming-Yii Huang, Hsueh-Chiao Liu, Li-Chen Yen
1Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. cy614112@ms14.hinet.net.
Background:
The KRAS oncogene was one of the earliest discoveries of genetic alterations in colorectal and lung cancers. Moreover, KRAS somatic mutations might be used for predicting the efficiency of anti-EGFR therapeutic drugs. The purpose of this research was to improve Activating KRAS Detection Chip by using a weighted enzymatic chip array (WEnCA) platform to detect activated KRAS mutations status in the peripheral blood of non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC) patients in Taiwan.
Methods:
Our laboratory developed an Activating KRAS Detection Chip and a WEnCA technique that can detect activated KRAS mutation status by screening circulating cancer cells in the surrounding bloodstream. We collected 390 peripheral blood samples of NSCLC patients (n = 210) and CRC patients (n = 180) to evaluate clinical KRAS activation using this gene array diagnosis apparatus, an Activating KRAS Detection Chip and a WEnCA technique. Subsequently, we prospectively enrolled 88 stage III CRC patients who received adjuvant FOLFOX-4 chemotherapy with or without cetuximab. We compared the chip results of preoperative blood specimens and their relationship with disease control status in these patients.
Results:
After statistical analysis, the sensitivity of WEnCA was found to be 93%, and the specificity was found to be 94%. Relapse status and chip results among the stage III CRC patients receiving FOLFOX-4 plus cetuximab (n = 59) and those receiving FOLFOX-4 alone (n = 29) were compared. Among the 51 stage III CRC patients with chip negative results who were treated with FOLFOX-4 plus cetuximab chemotherapy, the relapse rate was 33.3%; otherwise, the relapse rate was 48.5% among the 23 out of 88 patients with chip negative results who received FOLFOX-4 alone. Negative chip results were significantly associated to better treatment outcomes in the FOLFOX-4 plus cetuximab group (P = 0.047).
Conclusions:
The results demonstrated that the WEnCA technique is a sensitive and convenient technique that produces easy-to-interpret results for detecting activated KRAS from the peripheral blood of cancer patients. We suggest that the WEnCA technique is also a potential tool for predicting responses in CRC patients following FOLFOX-4 plus cetuximab chemotherapy.
Insights
The weighted enzymatic chip array (WEnCA) technique accurately detects activated KRAS mutations in blood for non-small-cell lung and colorectal cancers. This method shows promise for predicting treatment response in colorectal cancer patients receiving FOLFOX-4 plus cetuximab.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- KRAS oncogene mutations are early genetic alterations in colorectal and lung cancers.
- KRAS mutations can predict the efficacy of anti-EGFR therapies.
- Detecting activated KRAS mutations in peripheral blood is crucial for personalized cancer treatment.
Purpose of the Study:
- To enhance the Activating KRAS Detection Chip using a weighted enzymatic chip array (WEnCA) platform.
- To detect activated KRAS mutation status in the peripheral blood of non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC) patients.
- To evaluate the WEnCA technique's performance and its potential in predicting treatment outcomes.
Main Methods:
- Developed an Activating KRAS Detection Chip and WEnCA technique for screening circulating tumor cells.
- Collected and analyzed 390 peripheral blood samples from NSCLC and CRC patients.
- Prospectively studied 88 stage III CRC patients undergoing FOLFOX-4 chemotherapy with or without cetuximab, comparing chip results with disease control status.
Main Results:
- The WEnCA technique demonstrated high sensitivity (93%) and specificity (94%) in detecting activated KRAS mutations.
- In stage III CRC patients receiving FOLFOX-4 plus cetuximab, negative WEnCA chip results were significantly associated with better treatment outcomes (P=0.047).
- Relapse rates were lower in patients with negative chip results treated with FOLFOX-4 plus cetuximab compared to those treated with FOLFOX-4 alone.
Conclusions:
- The WEnCA technique is a sensitive, convenient, and easy-to-interpret method for detecting activated KRAS in cancer patient blood.
- WEnCA shows potential as a predictive tool for treatment response in colorectal cancer patients receiving FOLFOX-4 plus cetuximab chemotherapy.
