Liquid Biopsy Using Ascites and Pleural Effusion Supernatant for Genomic Profiling in Gastrointestinal and Lung Cancers

Background: Precision medicine highlights the importance of incorporating molecular genetic testing into standard clinical care. Next-generation sequencing (NGS) can detect cancer-specific gene mutations, and molecular targeted drugs can be designed to be effective for one or more specific gene mutations. For patients with special site metastasis, it is particularly important to use appropriate samples for genetic profiling test.Methods: Tissues, plasma, ascites (ASC) supernatants, pleural effusion (PE) samples from gastrointestinal (GI) patients with peritoneal metastasis and lung cancer patients with pleural metastasis were collected for comprehensive genomic profiling. The sample were performed on next-generation sequencing (NGS) using 59 or 1021 cancer-relevant genes panel. Results: The study enrolled 156 tissues, 188 plasma, 45 ascites supernatants, and 1 pleural effusion in 304 GI group and 446 pleural effusion supernatants, 122 tissues, 389 plasma, 45 pleural effusion sediments in 407 lung cancer group. The MSAF were significantly higher in ASC and PE supernatant than plasma ctDNA (50.18% ± 32.03% vs 12.31% ± 19.90%, p < 0.0001 and 33.74% ± 28.34% vs 6.28% ± 12.17%, p < 0.0001, respectively). ASC supernatant had a higher actionable mutation rate than plasma. ASC supernatant accounts for more actionable alterations than plasma ctDNA in 26 paired samples. PE supernatant had higher total actionable mutation rate than plasma (80.3% vs 48.4%, p < 0.05). PE supernatant had a higher frequency of uncommon variations than plasma no matter had distant organ metastasis. Conclusion: ASC and PE supernatants could be better alternatives when tumor tissues are not available in the real world, especially in patients who have only peritoneal or pleural metastases.