Surface-Enhanced Raman Spectroscopy of Pretreated Plasma Samples Predicts Disease Recurrence in Muscle-Invasive Bladder Cancer Patients Undergoing Neoadjuvant Chemotherapy and Radical Cystectomy

Hongyang Qian,1,* Yiqiu Wang,1,* Zehua Ma,1,* Lei Qian,1 Xiaoguang Shao,1 Di Jin,1 Ming Cao,1 Shupeng Liu,2 Haige Chen,1 Jiahua Pan,1 Wei Xue1 1Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People’s Republic of China; 2Shanghai Institute for Advanced Communication and Data Science, Key Laboratory of Specialty Fiber Optics and Optical Access Networks, School of Communication and Information Engineering, Shanghai University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Xue; Jiahua Pan, Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 1630 Dongfang Road, Shanghai, 200127, People’s Republic of China, Tel +86 21 6838 3375, Email xuewei@renji.com; panjiahua@renji.comObjective: To explore the value of surface-enhanced Raman spectroscopy analysis of pretreated plasma samples in prediction of bladder cancer (BCa) recurrence after neoadjuvant chemotherapy (NAC) and radical cystectomy (RC).Patients and Methods: SERS was used to analyze plasma samples collected before biopsy and treatment in BCa patients undergoing NAC and RC. The value of clinicopathological parameters and distinctive SERS peaks in the prediction of disease recurrence were analyzed in Cox regression proportional hazard analysis and Log rank test. Principal component analysis and linear discriminant analysis (PCA-LDA) were employed to process spectral data and construct diagnostic algorithms.Results: A total of 88 patients with 440 plasma SERS spectra were collected. The SRES spectra from recurrent patients were compared with patients who remained recurrence free. The SERS demonstrated higher levels of circulating free nucleic acid components in recurrent population, which is represented by significantly higher intensities at SERS peaks of 725 cm− 1, 1328 cm− 1 and 1455 cm− 1. The SERS also detected signific