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. 2023 Sep 3;23(1):629.
doi: 10.1186/s12903-023-03311-5.

High expression of HSP60 and survivin predicts poor prognosis for oral squamous cell carcinoma patients

Ying Zhou  1 , Yaoxiang Tang  1 , Jiadi Luo  1 , Yang Yang  1 , Hongjing Zang  1 , Jian Ma  2 , Songqing Fan  1 , Qiuyuan Wen  3
Affiliations

High expression of HSP60 and survivin predicts poor prognosis for oral squamous cell carcinoma patients

Ying Zhou et al. BMC Oral Health. .

Abstract

Background: HSP60 is a heat shock proteins (HSPs) family member and help mitochondrial protein to fold correctly. Survivin is one of the inhibitors of apoptosis protein family member, which plays a significant part in cancer progression. They were capable of forming HSP60-survivin complexes and involved in the development of various tumors.

Methods: The Cancer Genome Atlas (TCGA) database demonstrated that HSP60 and survivin and their correlation on mRNA expression level with OSCC patients. Besides, expression of HSP60 and survivin proteins was studied utilizing immunohistochemistry in tissue microarrays (TMA) in OSCC and in adjacent non-cancerous squamous epithelium (Non-CCSE) tissues.

Results: Significantly increased levels of HSP60 and survivin in most cancers compared to normal tissue by pan-cancer analysis. HSP60 and survivin proved a significantly increased expression in OSCC samples compared to Non-CCSE both on mRNA and protein (both P < 0.05). Additionally, elevated HSP60 displayed a positive correlation with survivin in terms of mRNA and protein expression levels (all P < 0.001). Patients with OSCC who had advanced clinical stage or lymph node metastasis (LNM) showed higher HSP60 expression (P = 0.004, P = 0.006, respectively). Higher levels of the proteins HSP60 and survivin were significantly inversely correlated relationship with OSCC patients' overall survival rates in multivariate survival analysis (P = 0.018, P = 0.040). From the above results, overexpression of HSP60 and survivin protein may serve as independent biomarkers predicting poor prognosis in OSCC.

Conclusions: Elevated HSP60 and survivin might be served as novel poor prognosis biomarkers for surgically resected OSCC patients.

Keywords: Biomarker; HSP60; Oral squamous cell carcinoma; Prognosis; Survivin.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Analysis of HSP60 and survivin expression in pan-cancer Comparison of mRNA expression of HSP60 (A) and survivin (B) between tumor and normal tissues. Both HSP60 and survivin are upregulated in most malignant tumors. Adrenocortical carcinoma (ACC); Bladder Urothelial Carcinoma (BLCA); Breast invasive carcinoma (BRCA); Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC); Cholangio carcinoma (CHOL); Colon adenocarcinoma (COAD); Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC); Esophageal carcinoma (ESCA); Glioblastoma multiforme (GBM); Head and Neck squamous cell carcinoma (HNSC); Kidney Chromophobe (KICH); Kidney renal clear cell carcinoma (KIRC); Kidney renal papillary cell carcinoma(KIRP); Acute Myeloid Leukemia (LAML); Brain Lower Grade Glioma (LGG); Liver hepatocellular carcinoma (LIHC); Lung adenocarcinoma (LUAD); Lung squamous cell carcinoma (LUSC); malignant mesothelioma (MESO); Ovarian serous cystadenocarcinoma (OV); Pancreatic adenocarcinoma (PAAD); Pheochromocytoma and Paraganglioma (PCPG); Prostate adenocarcinoma (PRAD); Rectum adenocarcinoma (READ) ; Sarcoma (SARC); Skin Cutaneous Melanoma (SKCM); Stomach adenocarcinoma (STAD); Testicular Germ Cell Tumors (TGCT); Thyroid carcinoma(THCA); Thymoma (THYM); Uterine Corpus Endometrial Carcinoma (UCEC); Uterine Carcinosarcoma (UCS); Uveal Melanoma (UVM).
Fig. 2
Fig. 2
Bioinformatics analysis of HSP60 and survivin in OSCC mRNA expression of HSP60 (A) and survivin (B) was significantly higher in OSCC tissues than that in NC (normal control) tissues (Both P < 0.0001). HSP60 was positively correlated with survivin in mRNA level (C) (r = 0.488, P < 0.001)
Fig. 3
Fig. 3
Expression of HSP60 and survivin in OSCC and Non-CCSE were detected by IHC Expression of HSP60 and survivin in OSCC and Non-CCSE tissues by IHC. Strong positive cytoplasm staining and weak staining of HSP60 in OSCC patients (A and D). Strong positive nuclear staining and weak staining of survivin in OSCC patients (B and E). Negative staining of HSP60 (C) and survivin (F) proteins was found in Non-CCSE.
Fig. 4
Fig. 4
The comparison of expression of HSP60 and survivin in OSCC compared to the Non-CCSE The expression of HSP60 and survivin in OSCC was significantly higher than those in Non-CCSE (P < 0.002, P = 0.028, respectively)
Fig. 5
Fig. 5
Kaplan-Meier cures for overall survival of OSCC patients with expression of HSP60 and survivin (A) OSCC patients with high expression of HSP60 showed worse overall survival rates compared to patients with low HSP60 expression (P = 0.004, two sided). (B) There was no statistical significance of overall survival rate between OSCC patients with different phenotype of survivin protein (P = 0.599, two sided). (C) Overall survival rate of OSCC patients with clinical stage I-II is higher than that of patients with clinical stage III-IV (P = 0.009, two sided). (D) Overall survival rate of OSCC patients with lymph node metastasis was significantly lower than that of patients without lymph node metastasis. (P = 0.025, two sided)
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