Tomm34 is commonly expressed in epithelial ovarian cancer and associates with tumour type and high FIGO stage

Abstract

Background: Increased activity of the chaperones Hsp70 and Hsp90 is a common feature of solid tumours. Translocase of the outer mitochondrial membrane 34 (Tomm34) is a cochaperone of both Hsp70 and Hsp90 that was found to be overexpressed in colorectal, hepatocellular, lung and breast carcinomas. The expression profile of Tomm34 in ovarian cancer has not been investigated. Therefore, the aim of the current study was to investigate the expression pattern of Tomm34 in ovarian carcinomas and analyse its correlation with clinico-pathological parameters. Results: Epithelial ovarian cancers (140) were histologically classified based on their morphology and graded into two types comprising 5 histologic subgroups. Type I carcinomas comprise low grade serous (LGSC), clear cell (CCOC) and endometrioid (ENOC), type II comprises high grade serous carcinomas (HGSC) and solid, pseudoendometrioid, transitional carcinomas (SET). Tomm34 was more highly expressed in type II than type I carcinomas (p < 0.0001). Comparing tumours based on the mutation in the TP53 gene revealed similar results, where mutant tumours exhibited significantly higher levels of Tomm34 (p < 0.0001). The decreased levels of Tomm34 in type I carcinomas were particularly evident in clear cell and mucinous carcinomas. The expression of Tomm34 was also positively correlated with FIGO stage (r = 0.23; p = 0.007). Tomm34 levels also indicated poor prognosis for patients with mutant p53. Conclusions: Our data indicate that Tomm34 is commonly expressed at high levels in epithelial ovarian cancers, except for the clear cell and mucinous subtypes. The expression of Tomm34 corresponds with the dualistic model of ovarian cancer pathogenesis where high grade, type II tumours exhibit higher expression of Tomm34 in contrast to type I tumours. These data are also comparable to the previous findings that Tomm34 is a marker of progression and poor prognosis in human cancer.

Identification of Mitochondrial-Related Prognostic Biomarkers Associated With Primary Bile Acid Biosynthesis and Tumor Microenvironment of Hepatocellular Carcinoma

“…TOMM34 is a protein located in the outer membrane of mitochondria (TOMM), which plays a role in importing preprotein into the mitochondria ( 58 ). A previous study found that TOMM34 was overexpressed in colon cancer ( 59 ), ovarian cancer ( 60 ), and breast cancer ( 61 ) and served as a biomarker of the progression and poor prognosis of ovarian and breast cancer. However, to date, the role of ACOT7, ADPRHL2, ATAD3A, FAM72A, PDSS1, RAD51C, and TOMM34 in HCC almost unclear.…”

DIA-Based Proteomics Identifies IDH2 as a Targetable Regulator of Acquired Drug Resistance in Chronic Myeloid Leukemia

“…Located in the cytoplasm, TOMM34 is known to interact with HSP70 and HSP90 and regulate the activity of ATPase ( 55 ). High expression of TOMM34 has been found in colon cancer ( 56 ), breast cancer ( 57 ), and ovarian cancer ( 58 ).…”

High Expression of Tomm34 and Its Correlations With Clinicopathology in Oral Squamous Cell Carcinoma

“…As we known, TP53 mutation is a famous carcinogenetic factor of OSCC, which leads to the instability of the tumor genome [ 37 ]. Tomm34 expression levels indicates poor prognosis for p53-mutant epithelial ovarian cancer [ 20 ]. Our bioinformatic analysis indicated that higher expression of Tomm34 was detected in TP53-mutant OSCC compared with TP53-nonmutant OSCC and normal tissue ( p < 0.001) ( Supplementary Figure S1 ), and further research will be required to elucidate the regulation mechanisms.…”

“…Tomm34 can interact with Hsp70 and Hsp90 to form Hsp70-Tomm34-Hsp90 complex, which acts as a co-chaperon of Hsp70 and Hsp90 to regulate its function [ 13 , 14 ]. Recent studies showed high levels of Tomm34 expressed in colorectal cancer [ 15 ], hepatocellular carcinoma [ 16 ], bladder cancer [ 17 ], breast cancer [ 18 , 19 ] epithelial ovarian cancer [ 20 ] and colon cancer [ 21 ] compared to their normal tissue counterparts. However, the expression of Tomm34 in oral squamous cell carcinoma primary tumor has not been reported and its role in OSCC is still unclear.…”