Euclidean distance-based Raman spectroscopy (EDRS) for the prognosis analysis of gastric cancer: A solution to tumor heterogeneity

The prognosis analysis of gastric cancer is critical for selection of treatments and development of advanced therapeutic methods. A prognosis approach that is accurate, fast, convenient, and of low cost for gastric cancers is in high demand. Raman spectroscopy is a label-free and non-destructive technique to provide molecular fingerprints of biological samples, holding promises for cancer prognosis. However, the major challenge of gastric cancer prognosis lies in the widely existing tumor heterogeneity, which leads to unexpected spectral variations within one type of samples. In this work, we have developed the Euclidean distance (ED)-based Raman spectroscopy (EDRS) method for the prognosis analysis of gastric cancer to eliminate the influence of tumor heterogeneity. Raman spectra were first collected on the slices of paraffin-preserved tumor tissues from gastric cancer patients. A standard spectrum to represent the ‘worst prognostic tumor cells’ was then established. The similarity between each spectrum of tissues and the standard spectrum was assessed by ED, to provide a direct assessment on the prognosis status. We have successfully classified the patients into poor and favorable prognosis groups, either based on the averaged regional ED values (sensitivity of 75 %, specificity of 96.8 %), or based on the minimal ED values at the patient level (sensitivity of 90 %, specificity of 100 %). EDRS was also investigated for survival analysis (AUC = 0.955), much better than the commonly applied post-neoadjuvant therapy (ypTNM) category (AUC = 0.718). Our work highlights EDRS as a rapid, accurate, low-cost and robust tool for heterogeneous cancer-related prognosis assessment and survival prediction, providing new insights for spectroscopic tumor analysis.