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The differential expression of chromosome 12 open reading frame 75 (C12orf75) is closely related with cancer progression. Here, we studied the expression levels of C12orf75 and investigated its prognostic value in various cancers across distinct datasets including ONCOMINE, PrognoScan, GEPIA, and TCGA. The correlation between genetic alteration of C12orf75 and immune infiltration was investigated using the cBioPortal and TIMER databases. RNA interference was used to verify the influence of C12orf75 knockdown on the biological phenotype o