Finding Predictive Biomarkers For Trastuzumab Resistance In A Breast Cancer Cell Line

Breast cancer has the highest incidence and mortality rate among all cancers in female globally. Thanks to the advancement in methods of early detecting and new treatments, the mortality declines steadily since 1980s. As one of the new treatment methods, the anti-HER2 Trastuzumab is a milestone in the revolution of adjacent therapy. However, drug resistance or poor response to Trastuzumab stood out as the major challenge for the treatment of breast cancer. People tend to find predicative biomarkers that can tell whether the treatment may fail or not. Up to now, most of these biomarkers were screened based on the mechanism of Trastuzumab and only a limited part of them have been clinically validated. In this research, we tried to screening potential biomarkers for Trastuzumab-resistance by combining data from public-available databases with the results from our own Trastuzumab-resistant breast cancer cells. We believe this strategy would be superior over traditional strategies in finding predictive biomarkers and intervention targets. Therefore, we performed a RNA-Seq to analyze the genome-wide changes in breast cancer cells resistant to Trastuzumab and combined it with TCGAgene expression data for a co-expression analysis. Indeed, we found a list of differential expressed genes with potential functions. Among them, KLK10 was verified as a potentially useful biomarker. We also found that KLK10 could be a promising target to reverse Trastuzumab resistance. In conclusion, results from this research would provide new clues to screen predictive biomarkers and intervention target for Trastuzumab resistance.