In summary, while previous studies established the diagnostic and prognostic value of SHOX2 and SEPTIN9 in both ascites and pleural effusions, our study introduces the novel combination of four genes (SHOX2, RASSF1A, SEPTIN9, and HOXA9) in ascites, demonstrating superior diagnostic sensitivity without compromising specificity. Here, SEPTIN9 is linked to Pleural effusion.