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血清山梨糖醇脫氫酶作為肝細(xì)胞癌手術(shù)切除后新的預(yù)后因素

發(fā)表日期：2022-03-09

Serum Sorbitol Dehydrogenase as a Novel Prognostic Factor for Hepatocellular Carcinoma after Surgical Resection

血清山梨糖醇脫氫酶作為肝細(xì)胞癌手術(shù)切除后新的預(yù)后因素

A large percentage of patients with hepatocellular carcinoma (HCC) who undergo surgical resection experience a recurrence of their disease. Therefore, predicting recurrence after resection for HCC is crucial to select appropriate surgical candidates. The aim of this study was to determine if serum sorbitol dehydrogenase (SORD) levels, an enzyme that reflects liver damage, was associated with the length of recurrence-free survival. This study’s findings that serum SORD levels ≥15 ng/mL were associated with a shorter recurrence-free survival might help to determine which patients are better candidates for surgery in HCC. Moreover, baseline serum SORD and alpha-fetoprotein (AFP) levels could better predict the outcome when used in combination, with patients having both elevated SORD (≥15 ng/mL) and AFP (≥400 ng/mL) levels having a particularly poor prognosis. Therefore, incorporating serum SORD along with AFP levels in clinical practice may raise predictability of prognosis in HCC patients.

大部分接受手術(shù)切除的肝細(xì)胞癌 (HCC) 患者會出現(xiàn)疾病復(fù)發(fā)。因此，預(yù)測 HCC 切除后的復(fù)發(fā)對于選擇合適的手術(shù)候選者至關(guān)重要。本研究的目的是確定血清山梨醇脫氫酶 (SORD) 水平（一種反映肝損傷的酶）是否與無復(fù)發(fā)生存期的長度相關(guān)。本研究發(fā)現(xiàn)血清 SORD 水平≥15 ng/mL 與較短的無復(fù)發(fā)生存期相關(guān)，這可能有助于確定哪些患者更適合 HCC 手術(shù)。此外，當(dāng)聯(lián)合使用時，基線血清 SORD 和甲胎蛋白 (AFP) 水平可以更好地預(yù)測結(jié)果，SORD（≥15 ng/mL）和 AFP（≥400 ng/mL）水平升高的患者預(yù)后特別差。因此，在臨床實踐中結(jié)合血清 SORD 和 AFP 水平可能會提高 HCC 患者預(yù)后的可預(yù)測性。

高效搖瓶

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer with a high prevalence and incidence in Asia [1]. Liver resection is the treatment of choice for patients with early-stage or resectable HCC [2], but the results are unsatisfactory. The survival rate remains low for these patients due to the high recurrence rate. The 5-year recurrence rate was 68% in patients with a single HCC (≤2 cm) after hepatectomy [3], and HCC recurrence adversely affects the long-term survival of patients [4,5]. Therefore, predicting recurrence after resection for HCC is crucial in order to select appropriate surgical candidates. Previous studies have noted that preoperative serum alpha-fetoprotein (AFP) levels and various histological features of tumors such as tumor size and microvascular invasion are independent predictors of recurrence after resection [6,7,8,9,10,11,12]. However, histological features are limited since they cannot be evaluated preoperatively. Moreover, AFP has a relatively low sensitivity and specificity for accurately predicting HCC [13], and the association of AFP with surgical outcome has been contradictory [14,15]. As a result, there is still a need for a novel prognostic marker to predict outcomes in patients with HCC after resection.

Inflammation, necrosis, and liver regeneration induced by various liver diseases play an important role in promoting HCC development [16]. More than 90% of HCCs develop in the context of hepatic damage and inflammation, making it a clear example of inflammation-related cancer. Sorbitol dehydrogenase (SORD), an enzyme in the polyol pathway converting sorbitol into fructose, reflects liver damage [17,18,19,20,21]. SORD is concentrated primarily in the liver similar to alanine aminotransferase (ALT) [22]. In patients with liver diseases including hepatitis, cirrhosis, and HCC, serum levels of SORD are elevated along with elevated levels of serum aspartate aminotransferase (AST) and ALT [23,24].

細(xì)胞工廠

The polyol pathway, which produces sugar alcohols by aldo-keto reductase and SORD contributes to cancer development and aggressiveness [25,26]. In the previous study, blood sugar alcohol levels such as sorbitol increased steadily from healthy controls to patients with chronic liver disease and finally, HCC patients [27]. Moreover, increased expression of aldo-reductase and SORD was observed in various cancers such as liver, breast, and colorectal cancers [25,28]. A recent proteomics study found that the levels of SORD expression in tumor tissue were significantly associated with prognosis in patients with HCC [29,30], implying that serum SORD levels may be used as a prognostic marker in these patients. However, there has been no study evaluating the association between preoperative serum SORD levels and surgical outcomes of patients with HCC. This study aimed to evaluate the association between preoperative serum levels of SORD and HCC recurrence in patients with early-stage HCC after curative resection.

肝細(xì)胞癌 (HCC) 是最常見的原發(fā)性肝癌類型，在亞洲具有較高的患病率和發(fā)病率 [ 1 ]。肝切除是早期或可切除 HCC 患者的首選治療方法 [ 2 ]，但效果并不理想。由于高復(fù)發(fā)率，這些患者的存活率仍然很低。肝切除術(shù)后單發(fā) HCC（≤2 cm）患者的 5 年復(fù)發(fā)率為 68% [ 3 ]，HCC 復(fù)發(fā)對患者的長期生存產(chǎn)生不利影響 [ 4 , 5]。因此，預(yù)測 HCC 切除后的復(fù)發(fā)對于選擇合適的手術(shù)候選者至關(guān)重要。先前的研究指出，術(shù)前血清甲胎蛋白 (AFP) 水平和腫瘤的各種組織學(xué)特征，如腫瘤大小和微血管侵犯是切除術(shù)后復(fù)發(fā)的獨立預(yù)測因素 [ 6 , 7 , 8 , 9 , 10 , 11 , 12 ]。然而，組織學(xué)特征是有限的，因為它們無法在術(shù)前進(jìn)行評估。此外，AFP 對準(zhǔn)確預(yù)測 HCC 的敏感性和特異性相對較低 [ 13 ]，而 AFP 與手術(shù)結(jié)果的關(guān)聯(lián)一直是矛盾的[13]。14、15 ]。_ 因此，仍然需要一種新的預(yù)后標(biāo)志物來預(yù)測 HCC 患者切除后的預(yù)后。

各種肝病引起的炎癥、壞死和肝再生在促進(jìn)HCC發(fā)展中發(fā)揮著重要作用[ 16 ]。超過 90% 的 HCC 在肝損傷和炎癥的背景下發(fā)展，使其成為炎癥相關(guān)癌癥的明顯例子。山梨醇脫氫酶 (SORD) 是多元醇途徑中將山梨醇轉(zhuǎn)化為果糖的一種酶，它反映了肝損傷 [ 17 , 18 , 19 , 20 , 21 ]。劍主要集中在肝臟中，類似于丙氨酸氨基轉(zhuǎn)移酶（ALT）[ 22]。在肝炎、肝硬化和 HCC 等肝病患者中，SORD 的血清水平隨著血清天冬氨酸氨基轉(zhuǎn)移酶 (AST) 和 ALT 水平的升高而升高 [ 23 , 24 ]。

通過Aldo-Keto還原酶和SORD產(chǎn)生糖醇的多元醇途徑有助于癌癥發(fā)育和侵襲性[ 25,26 ]。在以前的研究中，山梨醇等血糖酒精水平穩(wěn)定地從健康對照增加對慢性肝病的患者，最后，HCC患者[ 27 ]。此外，在各種癌癥（如肝臟，乳腺和結(jié)腸直腸癌）中觀察到aldo-yductase和Sord的表達(dá)增加[ 25,28 ]。最近的蛋白質(zhì)組學(xué)研究發(fā)現(xiàn)，腫瘤組織中的SORD表達(dá)水平與HCC患者的預(yù)后顯著相關(guān)[ 29,30]，這意味著血清 SORD 水平可用作這些患者的預(yù)后標(biāo)志物。然而，尚無研究評估術(shù)前血清 SORD 水平與 HCC 患者手術(shù)結(jié)果之間的關(guān)系。本研究旨在評估治療切除術(shù)后早期HCC患者術(shù)前血清和HCC復(fù)發(fā)性術(shù)前血清水平的關(guān)聯(lián)。

PETG血清培養(yǎng)基瓶

In conclusion, a baseline, elevated preoperative serum SORD level (≥15 ng/mL) was significantly associated with poor prognosis in patients with HCC after curative-intend resection. Moreover, baseline serum SORD and AFP levels could better predict the outcome, with patients having both elevated SORD (≥15 ng/mL) and AFP (≥400 ng/mL) levels having a particularly poor prognosis. Based on these findings, incorporating serum SORD along with AFP levels in clinical practice may assist with decision-making regarding appropriate surgical candidates and avoiding unnecessary surgery in patients with an expected poor survival.

總之，基線、術(shù)前血清 SORD 水平升高（≥15 ng/mL）與 HCC 患者根治性切除術(shù)后預(yù)后不良顯著相關(guān)。此外，基線血清 SORD 和 AFP 水平可以更好地預(yù)測結(jié)果，SORD（≥15 ng/mL）和 AFP（≥400 ng/mL）水平升高的患者預(yù)后特別差?；谶@些發(fā)現(xiàn)，在臨床實踐中結(jié)合血清 SORD 和 AFP 水平可能有助于就合適的手術(shù)候選者做出決策，并避免對預(yù)期生存率較差的患者進(jìn)行不必要的手術(shù)。