Low‐mass‐ion discriminant equation: A new concept for colorectal cancer screening

Blood metabolites can be detected as low‐mass ions (LMIs) by mass spectrometry (MS). These LMIs may reflect the pathological changes in metabolism that occur as part of a disease state, such as cancer. We constructed a LMI discriminant equation (LOME) to investigate whether systematic LMI profiling might be applied to cancer screening. LMI information including m/z and mass peak intensity was obtained by five independent MALDI‐MS analyses, using 1,127 sera collected from healthy individuals and cancer patients with colorectal cancer (CRC), breast cancer (BRC), gastric cancer (GC) and other types of cancer. Using a two‐stage principal component analysis to determine weighting factors for individual LMIs and a two‐stage LMI selection procedure, we selected a total of 104 and 23 major LMIs by the LOME algorithms for separating CRC from control and rest of cancer samples, respectively. CRC LOME demonstrated excellent discriminating power in a validation set (sensitivity/specificity: 93.21%/96.47%). Furthermore, in a fecal occult blood test (FOBT) of available validation samples, the discriminating power of CRC LOME was much stronger (sensitivity/specificity: 94.79%/97.96%) than that of the FOBT (sensitivity/specificity: 50.00%/100.0%), which is the standard CRC screening tool. The robust discriminating power of the LOME scheme was reconfirmed in screens for BRC (sensitivity/specificity: 92.45%/96.57%) and GC (sensitivity/specificity: 93.18%/98.85%). Our study demonstrates that LOMEs might be powerful noninvasive diagnostic tools with high sensitivity/specificity in cancer screening. The use of LOMEs could potentially enable screening for multiple diseases (including different types of cancer) from a single sampling of LMI information. What's new? It's challenging to screen for cancer, not least because the prevalence of specific cell types and gene expression patterns vary among patients and at different stages of disease. In this paper, the authors explore the idea of screening by profiling metabolites in the blood. Metabolites can be detected as low‐mass ions by mass spectrometry, and the authors created an algorithm to analyze these low‐mass ions as a cancer screening tool. The test showed high sensitivity and specificity when applied to colorectal cancer, breast cancer and gastric cancer, and thus it could be developed into an effective non invasive screening tool.