CLPTM1L is a prognostic and immune biomarker across human cancers validated in breast cancer

Also known as Cisplatin Resistance-Related Protein 9 (CRR9), CLPTM1L has been implicated in tumorigenesis and chemoresistance in several malignancies. However, an extensive pan-cancer evaluation of its expression profiles, clinical significance, regulatory mechanisms, and immunological roles remains lacking. This study aimed to systematically characterize CLPTM1L across human cancers and validate its oncogenic function in BRCA. Multi-omics datasets from TCGA, GTEx, HPA, and additional public repositories were compiled to investigate CLPTM1L expression profiles, diagnostic and prognostic value, genetic variations, epigenetic modifications, and immune correlations across 33 cancer types. To uncover the biological processes involved, pathway enrichment analyses were conducted. Data from GDSC and CTRP were used to evaluate correlations between CLPTM1L transcript levels and chemosensitivity. The differential expression and functional phenotype of CLPTM1L in BRCA were examined in vitro, and further verified in xenograft tumor models. Compared with normal tissues, CLPTM1L is markedly overexpressed across a wide range of cancers, and its level is tightly linked to clinicopathological stage, molecular subtype, and immune subtype. CLPTM1L transcript levels discriminated tumor from normal tissues with high accuracy in 9 cancer types (AUC > 0.9) and moderate accuracy in 15 others (AUC > 0.7). Multivariate Cox analysis identified high CLPTM1L expression as an independent adverse prognostic factor for OS in BRCA, LGG and LIHC, and as an independent favorable prognostic factor in KIRC. The prognostic nomogram constructed by integrating CLPTM1L expression and clinical features has good prediction accuracy. CLPTM1L expression was significantly associated with genomic instability markers and showed cancer-type-specific associations with stromal/immune infiltration and immunoregulatory gene signatures; whether these associations reflect gene-specific immunomodulation or overall immune-cell content requires further study. Enrichment analysis indicated that CLPTM1L predominantly participates in biological processes, including transcriptional regulation, DNA repair, substance metabolism, protein modification, and immune modulation. Analysis of drug sensitivity demonstrated that upregulation of CLPTM1L was associated with resistance to multiple anticancer compounds. CLPTM1L is markedly elevated in breast tumors. Knockdown suppresses proliferation, migration, and invasion in breast cancer cells, whereas overexpression enhances these malignant phenotypes. In vivo, CLPTM1L drives xenograft tumor growth, while knockdown inhibits it, confirming its oncogenic role. This study identifies CLPTM1L as a pan-cancer biomarker with diagnostic, prognostic, and immunological significance, and validates its oncogenic role in breast cancer, highlighting its potential as an actionable target in precision oncology.