Neurofilament light chain as a marker for neuronal damage: integrating in vitro studies and clinical findings in patients with oxaliplatin-induced neuropathy

Figures

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  Fig. 1. Oxaliplatin caused axonal damage to iPSC-derived sensory neurons in a concentration-dependent manner. Cells were exposed to control (sterile water) or 1, 10, or 20 µM oxaliplatin for 96 h. Cells were fixed, permeabilized, and labeled with NfL. Images were acquired using ImageXpress Pico Automated Imaging System with the 10X objective. Representative images are shown for the indicated concentrations. The experiment was performed with the iPSC donor A18945. iPSC, induced pluripotent stem cell; NfL, neurofilament light chain

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  Fig. 2. Neurofilament light chain (NfL) concentrations in medium from induced pluripotent stem cell-derived sensory neurons following oxaliplatin exposure. NfL concentrations were measured in the medium collected from induced pluripotent stem cell-derived sensory neurons after 96 h of exposure to oxaliplatin, and NfL concentration were subsequently measured using single-molecule array. The experiment included iPSC donors A18945 (donor 1) and WTC-11 (donor 2)

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  Fig. 3. Flowchart, including available data at 3-month and 6-month timepoints. *All patients are included in the mixed analysis

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  Fig. 4. Dot plot of NfL levels at the 3 timepoints for measurement (baseline, 3 months and 6 months) for patients who received oxaliplatin (oxa) and patients who did not receive oxaliplatin (non-oxa). Light blue box represents median and interquartile ranges. NfL: Neurofilament light chain protein

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  Fig. 5. Predicted NfL values at 3 timepoints in the two groups based on linear mixed model adjusted for age and diabetes visualized with 95% CIs

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  Fig. 6. Linear mixed model of predicted possible OIPN scores at 3 and 6 months adjusted for age and diabetes visualized with 95% CIs margins plot

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  Fig. 7. Scatterplot of possible OIPN score against changes in neurofilament light chain levels at the 6-month-timepoint compared to baseline (delta NfL). The black line indicates the best-fitted line for NfL measurements from the oxaliplatin group. N = 9 (oxaliplatin)