TIMM13 as a prognostic biomarker and associated with immune infiltration in skin cutaneous melanoma (SKCM)

Front Surg. 2022 Aug 17:9:990749. doi: 10.3389/fsurg.2022.990749. eCollection 2022.

Abstract

Objective: Providing protection against aggregation and guiding hydrophobic precursors through the mitochondria's intermembrane space, this protein functions as a chaperone-like protein. SLC25A12 is imported by TIMM8 as a result of its interaction with TIMM13. In spite of this, it is still unknown how TIMM13 interacts with skin cutaneous melanoma (SKCM) and tumor-infiltrating lymphocytes (TILs).

Methods: Aberrant expression of TIMM13 in SKCM and its clinical outcome was evaluated with the help of multiple databases, including the Xiantao tool (https://www.xiantao.love/), HPA, and UALCAN. TISIDB and Tumor Immune Estimation Resources (TIMER) databases were applied to explore the association between TIMM13 and tumor infiltration immune cells. OS nomogram was constructed, and model performance was examined. Finally, TIMM13 protein expression was validated by immunohistochemistry (IHC).

Results: TIMM13 expression was higher in SKCM samples than in peritumor samples. TIMM13 was strongly associated with sample type, subgroup, cancer stage, lymph node stage, and worse survival. Further, upregulation of TIMM13 was significantly associated with immunoregulators, and chemokines, as well as T cells, B cells, monocytes, neutrophils, macrophages, and T-cell regulators. An analysis of bioinformatic data uncovered that TIMM13 expression was strongly associated with PD1 (T-cell exhaustion marker). The nomogram showed good predictive performance based on calibration plot. TIMM13 was highly expressed in melanoma tissue samples than in normal samples.

Conclusion: In brief, TIMM13 may be a prognostic biomarker for SKCM. It might modulate the tumor immune microenvironment and lead to a poorer prognosis. In addition, it is necessary to study the targeted therapy of TIMM13.

Keywords: biomarker; cutaneous melanoma; prognosis; translocase of inner mitochondrial membrane 13 (TIMM13); tumor immune microenvironment.