Bourefis Asma, Berredjem Hajira, Djeffal Omar, Le Thi Khanh, Giusiano Sophie, Rocchi Palma
Laboratory of Applied Biochemistry and Microbiology, Department of Biochemistry, Faculty of Sciences, Badji Mokhtar-Annaba University, Annaba 23000, Algeria.
Private Medical Uro-Chirurgical Cabinet, Annaba 23000, Algeria.
Cancers (Basel). 2022 Sep 29;14(19):4773. doi: 10.3390/cancers14194773.
The screening of PCa is based on two tests, the total PSA test and the rectal examination. However, PSA is not specific for PCa stage confirmation, leading in false positive result and involving PCa over-diagnosis and over-treatment. HSP27 and Menin have been found to be overexpressed in a wide range of human cancers. Recent studies showed how HSP27 interacts with and stabilizes Menin to lead PCa progression and treatment resistance. The purpose of our study was to evaluate the correlation of HSP27 and Menin molecular expression, and their prognosis value in PCa with respect to clinicopathological features. Elisa was employed to measure serum HSP27 and Menin concentrations in 73 PCa patients and 80 healthy individuals. Immunohistochemistry (IHC) was used to determine HSP27 and Menin tissue expression in 57 tumors and 4 Benign Prostatic Hyperplasia (BPH) tissues. Serum HSP27 expression correlated with its tissue expression in all PCa patients, whereas serum Menin expression correlated only with tissue expression in aggressive PCa patients. Moreover, the results showed a positive correlation between HSP27 and Menin either in serum (r = 0.269; p = 0.021) or in tissue (r = 0.561; p < 0.0001). In aggressive PCa, serum expression of HSP27 and Menin was positively correlated (r = 0.664; R = 0.441; p = 0.001). The correlation between HSP27 and Menin expression in tissue was found only in patients with aggressive PCa (r = 0.606; R = 0.367; p = 0.004). Statistical analysis showed that the expression of both biomarkers was positively correlated with the hormone resistance or sensitivity, tumor aggressiveness, metastasis, Gleason Score, death and did not significantly correlate with age and PSA. Survival was illustrated by Kaplan−Meier curves; increased HSP27 and Menin expression correlated with shorter survival of PCa patients (p = 0.001 and p < 0.0001, respectively). Accuracy in predicting aggressiveness was quantified by the Area Under the Curve (AUC) of Receiver Operating Characteristic (ROC). We demonstrated that the combination of HSP27/Menin was statistically greater than PSA; it achieved an AUC of 0.824 (95% CI, 0.730−0.918; p < 0.0001). However, HSP27/Menin/PSA combination decreased the diagnostic value with an AUC of 0.569 (95% CI, 0.428−0.710; p = 0.645). Our work suggests the potential role of HSP27/Menin as diagnostic and prognostic biomarkers.
前列腺癌（PCa）的筛查基于两项检查，即总前列腺特异性抗原（PSA）检测和直肠指检。然而，PSA并非用于确诊PCa分期的特异性指标，会导致假阳性结果，进而引发PCa的过度诊断和过度治疗。热休克蛋白27（HSP27）和Menin已被发现在多种人类癌症中过度表达。最近的研究表明HSP27如何与Menin相互作用并使其稳定，从而导致PCa进展和治疗抵抗。我们研究的目的是评估HSP27和Menin分子表达的相关性，以及它们在PCa中相对于临床病理特征的预后价值。采用酶联免疫吸附测定（ELISA）法测定73例PCa患者和80名健康个体血清中HSP27和Menin的浓度。采用免疫组织化学（IHC）法测定57例肿瘤组织和4例良性前列腺增生（BPH）组织中HSP27和Menin的组织表达。在所有PCa患者中，血清HSP27表达与其组织表达相关，而血清Menin表达仅与侵袭性PCa患者的组织表达相关。此外，结果显示HSP27和Menin在血清中（r = 0.269；p = 0.021）和组织中（r = 0.561；p < 0.0001）均呈正相关。在侵袭性PCa中，HSP27和Menin的血清表达呈正相关（r = 0.664；R = 0.441；p = 0.001）。仅在侵袭性PCa患者中发现HSP27和Menin在组织中的表达存在相关性（r = 0.606；R = 0.367；p = 0.004）。统计分析表明，这两种生物标志物的表达均与激素抵抗或敏感性、肿瘤侵袭性、转移、 Gleason评分、死亡呈正相关，且与年龄和PSA无显著相关性。采用Kaplan−Meier曲线说明生存率；HSP27和Menin表达增加与PCa患者较短的生存期相关（分别为p = 0.001和p < 0.0001）。通过受试者操作特征曲线（ROC）的曲线下面积（AUC）对预测侵袭性的准确性进行量化。我们证明HSP27/Menin组合在统计学上优于PSA；其AUC为0.824（95%可信区间，0.730−0.918；p < 0.0001）。然而，HSP27/Menin/PSA组合降低了诊断价值，AUC为0.569（95%可信区间，0.428−0.710；p = 0.645）。我们的研究表明HSP27/Menin作为诊断和预后生物标志物的潜在作用。
