Dual-specificity phosphatase 6(DUSP6): a review of its molecular characteristics and clinical relevance in cancer

Mitogen-activated protein kinases(MAPKs) are the main regulators of cellular proliferation, growth, and survival in physiological or pathological conditions. Aberrant MAPK signaling plays a pivotal role in carcinogenesis, which leads to development and progression of human cancer. Dual-specificity phosphatase 6(DUSP6), a member of the MAPK phosphatase family, interacts with specifically targeted extracellular signal-regulated kinase 1/2 via negative feedback regulation in the MAPK pathway of mammalian cells. This phosphatase functions in a dual manner, pro-oncogenic or tumor-suppressive, depending on the type of cancer. To date, the tumor-suppressive role of DUSP6 has been demonstrated in pancreatic cancer, non-small cell lung cancer, esophageal squamous cell and nasopharyngeal carcinoma, and ovarian cancer. Its pro-oncogenic role has been observed in human glioblastoma, thyroid carcinoma, breast cancer, and acute myeloid carcinoma. Both roles of DUSP6 have been documented in malignant melanoma depending on the histological subtype of the cancer. Loss-or gain-of-function effects of DUSP6 in these cancers highlights the significance of this phosphatase in carcinogenesis. Development of methods that use the DUSP6 gene as a therapeutic target for cancer treatment or as a prognostic factor for diagnosis and evaluation of cancer treatment outcome has great potential. This review focuses on molecular characteristics of the DUSP6 gene and its role in cancers in the purview of development, progression, and cancer treatment outcome.

Dual-specificity Phosphatase 1 Deficiency Induces Endometrioid Adenocarcinoma Progression via Activation of Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase Pathway

Background： Previously, we reported that dual-specificity adenocarcinoma （EEA）. However, the role of DUSP1 medroxyprogesterone （MPA） are still unclear. phosphatase I （DUSPI） was differentially expressed in endometrioid in EEA progression and the relationship between DUSPI and Methods： The expression of DUSPI in EEA specimens was detected by immunohistochemical analysis. The effect of DUSPI on cell proliferation was analyzed by Cell Counting Kit 8 and colony formation assay, and cell migration was analyzed by transwell assay. MPA-induced DUSPI expression in EEA cells was measured by Western blot. Results： DUSPI expression was deficient in advanced International Federation of Gynecology and Obstetrics stage, high-grade and myometrial invasive EEA. In EEA cell lines （HeclA, Hecl B, RL952, and Ishikawa）, the DUSP1 expression was substantially higher in lshikawa cells than in other cell lines （P 〈 0.05）. Knockdown ofDUSP I promoted lshikawa cells proliferation, migration, and activation of mitogen-activated protein kinases/extracellular signal-regulated kinase （MAPK/Erk） pathway. MPA-induced DUSP1 expression and inhibited MAPK/Erk pathway in Ishikawa cells. Conclusions： Our data suggest that DUSP1 deficiency promotes EEA progression via MAPK/Erk pathway, which may be reversed by MPA, suggesting that DUSP I may serve as a potential therapeutic target for the treatment of EEA.

Protein tyrosine phosphatase non-receptor Ⅱ:A possible biomarker of poor prognosis and mediator of immune evasion in hepatocellular carcinoma

BACKGROUND The incidence of primary liver cancer is increasing year by year.In 2022 alone,more than 900000 people were diagnosed with liver cancer worldwide,with hepatocellular carcinoma(HCC)accounting for 75%-85%of cases.HCC is the most common primary liver cancer.China has the highest incidence and mortality rate of HCC in the world,and it is one of the malignant tumors that seriously threaten the health of Chinese people.The onset of liver cancer is occult,the early cases lack typical clinical symptoms,and most of the patients are already in the middle and late stage when diagnosed.Therefore,it is very important to find new markers for the early detection and diagnosis of liver cancer,improve the therapeutic effect,and improve the prognosis of patients.Protein tyrosine phosphatase non-receptor 2(PTPN2)has been shown to be associated with colorectal cancer,triple-negative breast cancer,non-small cell lung cancer,and prostate cancer,but its biological role and function in tumors remain to be further studied.AIM To combine the results of relevant data obtained from The Cancer Genome Atlas(TCGA)to provide the first in-depth analysis of the biological role of PTPN2 in HCC.METHODS The expression of PTPN2 in HCC was first analyzed based on the TCGA database,and the findings were then verified by immunohistochemical staining,quantitative real-time polymerase chain reaction(qRT-PCR),and immunoblotting.The value of PTPN2 in predicting the survival of patients with HCC was assessed by analyzing the relationship between PTPN2 expression in HCC tissues and clinicopathological features.Finally,the potential of PTPN2 affecting immune escape of liver cancer was evaluated by tumor immune dysfunction and exclusion and immunohistochemical staining.RESULTS The results of immunohistochemical staining,qRT-PCR,and immunoblotting in combination with TCGA database analysis showed that PTPN2 was highly expressed and associated with a poor prognosis in HCC patients.Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that PTPN2 was associated with various pathways,including cancer-related pathways,the Notch signaling pathway,and the MAPK signaling pathway.Gene Set Enrichment Analysis showed that PTPN2 was highly expressed in various immune-related pathways,such as the epithelial mesenchymal transition process.A risk model score based on PTPN2 showed that immune escape was significantly enhanced in the high-risk group compared with the low-risk group.CONCLUSION This study investigated PTPN2 from multiple biological perspectives,revealing that PTPN2 can function as a biomarker of poor prognosis and mediate immune evasion in HCC.

Soybean(Glycine max)rhizosphere organic phosphorus recycling relies on acid phosphatase activity and specific phosphorusmineralizing-related bacteria in phosphate deficient acidic soils

Bacteria play critical roles in regulating soil phosphorus(P) cycling. The effects of interactions between crops and soil P-availability on bacterial communities and the feedback regulation of soil P cycling by the bacterial community modifications are poorly understood. Here, six soybean(Glycine max) genotypes with differences in P efficiency were cultivated in acidic soils with long-term sufficient or deficient P-fertilizer treatments. The acid phosphatase(AcP) activities, organic-P concentrations and associated bacterial community compositions were determined in bulk and rhizosphere soils. The results showed that both soybean plant P content and the soil AcP activity were negatively correlated with soil organic-P concentration in P-deficient acidic soils. Soil P-availability affected the ɑ-diversity of bacteria in both bulk and rhizosphere soils. However, soybean had a stronger effect on the bacterial community composition, as reflected by the similar biomarker bacteria in the rhizosphere soils in both P-treatments. The relative abundance of biomarker bacteria Proteobacteria was strongly correlated with soil organic-P concentration and AcP activity in low-P treatments. Further high-throughput sequencing of the phoC gene revealed an obvious shift in Proteobacteria groups between bulk soils and rhizosphere soils, which was emphasized by the higher relative abundances of Cupriavidus and Klebsiella, and lower relative abundance of Xanthomonas in rhizosphere soils. Among them, Cupriavidus was the dominant phoC bacterial genus, and it was negatively correlated with the soil organic-P concentration. These findings suggest that soybean growth relies on organic-P mineralization in P-deficient acidic soils, which might be partially achieved by recruiting specific phoCharboring bacteria, such as Cupriavidus.

Analysis of alkaline phosphatase and γ-glutamyltransferase after radiofrequency ablation of primary liver cancer: A retrospective study

BACKGROUND Changes in alkaline phosphatase(ALP)andγ-glutamyltransferase(GGT)levels in patients with primary liver cancer(PLC)after radiofrequency ablation(RFA).Hepatocellular carcinoma is a malignant tumor with high incidence worldwide.As a common local treatment,RFA has attracted much attention for its efficacy and influence on liver function.AIM To investigate the effect of serum ALP and GGT levels on the prognosis of patients with PLC treated by RFA.METHODS The preoperative clinical data of 165 patients who were pathologically or clinically diagnosed with PLC and who received RFA in our hospital between October 2018 and June 2023 were collected.The chi-square test was used to compare the data between groups.The Kaplan-Meier method and Cox regression were used to analyze the associ-ations between serum ALP and GGT levels and overall survival,progression-free survival(PFS)and clinical characteristics of patients before treatment.RESULTS The 1-year survival rates of patients with normal(≤135 U/L)and abnormal(>135 U/L)serum ALP before treatment were 91%and 79%,respectively;the 2-year survival rates were 90%and 68%,respectively;and the 5-year survival rates were 35%and 18%,respectively.The difference between the two groups was statistically significant(P=0.01).Before treatment,the 1-year survival rates of patients with normal serum GGT levels(≤45 U/L)and abnormal serum GGT levels(>45 U/L)were 95%and 87%,the 2-year survival rates were 85%and 71%,and the 5-year survival rates were 37%and 21%,respectively.The difference between the two groups was statist-ically significant(P<0.001).Serum ALP[hazard ratio(HR)=1.766,95%confidence interval(95%CI):1.068-2.921,P=0.027]and GGT(HR=2.312,95%CI:1.367-3.912,P=0.002)is closely related to the overall survival of PLC patients after RF ablation and is an independent prognostic factor.The 1-year PFS rates were 72%and 50%,the 2-year PFS rates were 52%and 21%,and the 5-year PFS rates were 14%and 3%,respectively.The difference between the two groups was statistically significant(P<0001).The 1-year PFS rates were 81%and 56%in patients with normal and abnormal serum GGT levels before treatment,respectively;the 2-year PFS rates were 62%and 35%,respectively;and the 5-year PFS rates were 18%and 7%,respectively,with statistical significance between the two groups(P<0.001).The serum ALP concentration(HR=1.653,95%CI:1.001-2.729,P=0.049)and GGT(HR=1.949,95%CI:1.296-2.930,P=0.001)was closely associated with PFS after RFA in patients with PLC.The proportion of male patients with abnormal ALP levels is high,the Child-Pugh grade of liver function is poor,and the incidence of ascites is high.Among GGT-abnormal patients,the Child-Pugh grade of liver function was poor,the tumor stage was late,the proportion of patients with tumors≥5 cm was high,and the incidence of hepatic encephalopathy was high.CONCLUSION Serum ALP and GGT levels before treatment can be used to predict the prognosis of patients with PLC after RFA,and they have certain guiding significance for the long-term survival of patients with PLC after radiofrequency therapy.

MicroRNA-298 determines the radio-resistance of colorectal cancer cells by directly targeting human dual-specificity tyrosine(Y)-regulated kinase 1A

BACKGROUND Radiotherapy stands as a promising therapeutic modality for colorectal cancer(CRC);yet,the formidable challenge posed by radio-resistance significantly undermines its efficacy in achieving CRC remission.AIM To elucidate the role played by microRNA-298(miR-298)in CRC radio-resistance.METHODS To establish a radio-resistant CRC cell line,HT-29 cells underwent exposure to 5 gray ionizing radiation that was followed by a 7-d recovery period.The quantification of miR-298 levels within CRC cells was conducted through quantitative RT-PCR,and protein expression determination was realized through Western blotting.Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and proliferation by clonogenic assay.Radio-induced apoptosis was discerned through flow cytometry analysis.RESULTS We observed a marked upregulation of miR-298 in radio-resistant CRC cells.MiR-298 emerged as a key determinant of cell survival following radiation exposure,as its overexpression led to a notable reduction in radiation-induced apoptosis.Intriguingly,miR-298 expression exhibited a strong correlation with CRC cell viability.Further investigation unveiled human dual-specificity tyrosine(Y)-regulated kinase 1A(DYRK1A)as miR-298’s direct target.CONCLUSION Taken together,our findings underline the role played by miR-298 in bolstering radio-resistance in CRC cells by means of DYRK1A downregulation,thereby positioning miR-298 as a promising candidate for mitigating radioresistance in CRC.

Phosphorus Starvation-induced Expression of Leaf Acid Phosphatase Isoforms in Soybean

Leaf acid phosphatase (APase) activities of 274 soybean genotypes were surveyed under field conditions with two levels of P supplies, and a nutrient solution culture experiment with eight selected genotypes was subsequently conducted under greenhouse conditions to further characterize APase activity and its isoform expression induced by P starvation. Results from the field experiment showed that there was a great genotypic variation for leaf APase activity among the tested soybean genotypes from different origins, and APase activity in many of the tested genotypes (about 60%) was generally increased in the treatment without P fertilizer addition. Results from the nutrient solution culture experiment showed that APase activity in all the eight tested genotypes was generally enhanced by P starvation. Six isoforms of APases were detected in isoelectric focusing gels with samples from both young and old leaves. The activity of all the six isoforms was increased by P starvation, but no new APase isoform was induced. Our results suggest that leaf APase activity could serve as an enzymatic indicator of P starvation for soybean; the increase in leaf APase activity under low P stress was mainly caused by the increase in the activity of existing isoforms but not by the induction of new isoforms.

Ultracytochemical Localization of Acid Phosphatase in Nucellar Cells of Wheat During Degeneration

The distribution of acid phosphatase activity in nucellar cells of wheat ( Triticum aestivum L.) during degeneration has been studied using the lead precipitation method at the electron microscopic level. Acid phosphatase was localized in the slightly condensed nuclear chromatin in nucellar cells without any sign of ultrastructural degeneration. As the nucellar cells started degenerating, the enzyme activity in the cell was observed, in the order from small vacuoles to cell walls, mitochondria, plastids and endoplasmic reticulum. Enzyme activity was the highest in most components of the nucellar cells adjacent to the embryo sac where the degeneration of nucellar cells was the strongest, but it was not observed in the nuclei of the degenerated nucellar cells. The results indicated that the degeneration of nucellar cells was a progressive and orderly process and supported that the degeneration of nucellar cells was a programmed cell death.

Effects of Metal Ions and Organic Solvents on Alkaline Phosphatase from Rice-field Eel

[Objective]The mechanism of alkaline phosphatase（ALP） was studied to promote rice-field eel aquaculture industry. [ Method] The effects of effectors such as multiple metal ions and organic solvents on ALP in viscera of rice-field eel. [ Result] Na^＋ and K ^＋ didn＇t generate big influences on enzyme activity;Mg^2＋ and Ca^2＋ could promote ALP while Li^＋,Cu^2＋ and Zn^2＋ could restrain ALP enzyme activity. Both HPO4^2- and WO4^2- generated by en- zyme catalyzing disodium phenyl phosphate possessed strong inhibitory effects on emzymc, and 9.5 mmol/L HPO4^2 - would make enzyme activity decline by 13% while 9.5 mmol/L WO4^3- would make enzyme decline by 34%. The inhibition types of them were both competitive inhibition on enzyme activity. The organic solvents such as methanol, ethanol,ethylene glycol,isopropannl all generated influences on ALP and the order according to their inhibitory effects was isopropanol 〉 ethanol 〉 methanol 〉 ethylene glycol. [ Conclusion] The inflncnces of various effeetors on ALP aetivity of rice-field eel were studied from dynamics perspective to provide theoretical basis for further clarifying ALP mechanism.

Activities of Urease and Phosphatase in Integrated Vertical Flow Constructed Wetland and Purification Effect of Black and Malodorous River

[Objective]The activities of urease and phosphatase in integrated vertical flow constructed wetland and purification effect of black and malodorous river were studied.[Method]Honeycomb stone and soft filler were used as matrix,the biological grid integrated vertical flow constructed wetland system was built to strengthen treatment for black and malodorous river,and the activities of urease and phosphatase of two fillers in different functional areas of constructed wetland were tested to study the film formation property of two fillers in different functional areas.[Result]Both urease and phosphatase activities on biofilm of soft filler were significantly higher than on biofilm of honeycomb stone filler;indicating that choosing soft filler was more advantageous to the growth of biofilm;and urease activity had significant correlation with total nitrogen removal rate,while phosphatase activity had no significant correlation with total phosphorus removal rate.[Conclusion]This study provided evidences for utilizing the activities of urease and phosphatase to evaluate the purification effect of black and malodorous river and choose appropriate filler.

Dynamic Effects of PAEs on Soil Urease and Phosphatase

[Object] The study aimed to supply a reference for evaluating ecotoxicology of soil contaminated with phthalate acid esters(PAEs).[Method] The dynamic effects of DBP and DEHP on activities and kinetics parameters of urease and phosphatase in agro-soil contaminated artificially with DBP and DEHP were studied.[Result] The activities of urease and phosphatase were both inhibited significantly by higher contents of DBP and DEHP in soils compared with CK.The inhabitations increased with increasing DBP and DEHP c...

The Study on the Localization of Acid Phosphatase Activity During Spermiogenesis in Chinese Mitten-Handed Crab,Eriocheir sinensis

Ultrastructural cytochemical techniques and electron microscopy were used for localization of acid phosphatase activity during spermiogenesis in Eriocheir sinemsis. The results showed that： Acid phosphatase was synthesized in the endoplasmic reticulum in the early spermatids. The acid phosphatase was found gradually in nucleus, the membrane of acrosomal vesicle, the cytoplasmic region and the acrosomal tubule. And then the reaction product particles became thicker during the spermiogenesis. In the mature sperm, acid phosphatase was localized in the percutor organ slightly, but it was massive and compact in the acrosomal tubule.

Cantharidin and Its Analogues:Anticancer and Ser/Thr Protein Phosphatase Inhibitory Activities

This paper mainly describes the anticancer activities and Ser/Thr protein phosphatase inhibitory activities of cantharidin and its analogues.

Digestive enzyme and alkaline phosphatase activities during the early stages of Silurus soldatovi development

To provide a theoretical basis to improve the survival and growth rate and optimize diet of sheatfish （Silurus soldatovi）, the activities of certain digestive enzymes and alkaline phosphatases were investigated during larval development of one-ten day old individuals. Results indicated that sheatfish larva （～ three days after hatching） had high levels of alkaline protease activity, which peaked at five days old and dipped by eight days old, although the trend was generally upward. Acid protease activity at one-eight days old was low, after which it increased rapidly. Amylase activity reached the highest value at five days old, after which it began to decline. Lipase activity fluctuated markedly and showed two peaks at three-four days old and six-eight days old. Larval digestive enzyme activity and alkaline phosphatase activity were higher when fed live food than when fed an artificial diet. Throughout the early development process, alkaline protease activity was higher than acid protease, alkaline protease and amylase specific activity decreased significantly for eight-day-old transition larvae, while acid protease activity increased rapidly. These results indicate that the changes in digestive enzyme activity were relevant to digestive function conversion during fish larvae development. Alkaline phosphatase activity showed an upward trend over the first ten days of life, which indicated that the gastrointestinal function of sheatfish improved gradually.

Effects of heat shock on change of HSC70/HSP68,acid and alkaline phosphatases before and after rat partial hepatectomy

INTRODUCTIONOnly the liver has the great capability ofregeneration in mammal.Few hepatocytes are inthe phase of division in the normal liver of an adultmammal (including human beings),but theremaining hepatocytes can be induced to proliferatequickly by partial hepatectomy (PH),and,to somedegree,they stop dividing and re-differentiate intocells functioning as hepatocytes.This shows

Model based on γ-glutamyltransferase and alkaline phosphatase for hepatocellular carcinoma prognosis

AIM: To determine the prognostic value of alkaline phosphatase (ALP) and &#x003b3;-glutamyltransferase (GGT) for hepatocellular carcinoma (HCC) .

Soluble protein and acid phosphatase exuded by ectomycorrhizal fungi and seedlings in response to excessive Cu and Cd

Fungi and their symbionts can alleviate heavy metal stress by exuding soluble proteins and enzymes. This study examined the role of soluble protein and acid phosphatase （APase） exuded by Xerocomus chrysenteron, an ectomycorrhizal fungus, and the seedlings of its symbiont, Chinese pine （Pinus tabulaeformis）, under conditions of excessive Cu and Cd. The growth type showed that this poorly studied ectomycorrhizal fungus was capable of tolerating high concentrations of Cu, and may be useful in phytoremediation. X. chrysenteron grew well at 80 mg/L Cu, and the EC50 for Cd was 17.82 mg/L. X. chrysenteron also showed enhanced exudation of soluble protein in both isolated and inoculated cultivations under the influence of Cu and Cd. Soluble protein exudation, however, differed under Cu and Cd stress in isolates. In mediums containing Cu, soluble protein exudation increased with concentration, but in mediums containing Cd the content of soluble protein increased to a comparable level at all concentrations. This study demonstrated that soluble protein was related to heavy metal tolerance, although the different ions played different roles. While APase activity in exudates of fungi and seedlings decreased under Cu and Cd stress in comparison to the control, the APase activity in seedlings was maintained by inoculation. Thus, X. chrysenteron facilitated the ability of plant to maintain a normal nutrient uptake, and therefore to protect it from heavy metal toxicity.

Combination of serum gamma-glutamyltransferase and alkaline phosphatase in predicting the diagnosis of asymptomatic choledocholithiasis secondary to cholecystolithiasis

BACKGROUND Gamma-glutamyltransferase(GGT) is one of the most important laboratory tests for the evaluation of liver damage. Through a long-term clinical observation of patients with secondary asymptomatic choledocholithiasis, we found that most patients had abnormal GGT serum levels.AIM To investigate the combination of serum GGT and alkaline phosphatase(ALP) in predicting the diagnosis of asymptomatic choledocholithiasis secondary to cholecystolithiasis.METHODS In this retrospective cohort study, the clinical data of 829 patients with cholecystolithiasis admitted to the Third Affiliated Hospital of Zunyi Medical College from August 2014 to August 2017 were collected. Among these patients,151 patients had secondary asymptomatic choledocholithiasis and served as the observation group, and the remaining 678 cholecystolithiasis patients served as the control group. Serum liver function indexes were detected in both groups,and the receiver operating characteristic(commonly known as ROC) curves were constructed for markers showing statistical significances. The cutoff value,sensitivity, and specificity of each marker were calculated according to the ROC curves.RESULTS The overall incidence of asymptomatic choledocholithiasis secondary to cholecystolithiasis was 18.2%. The results of liver function indexes including serum aspartate aminotransferase, alanine aminotransferase, direct bilirubin and total bilirubin levels showed no significant differences between the two groups(P> 0.05). However, the serum GGT and ALP levels were significantly higher in the observation group than in the control group(P < 0.05). The ROC curve analysis showed that the area under the curve was 0.881(95%CI: 0.830-0.932), 0.647(95%CI: 0.583-0.711) and 0.923(0.892-0.953) for GGT, ALP, and GGT + ALP,respectively. The corresponding cut-off values of GGT and ALP were 95.5 U/L and 151.5 U/L, sensitivity were 90.8% and 65.1%, and specificity were 83.6% and59.8%, respectively. The sensitivity and specificity of GGT + ALP were 93.5% and85.1%, respectively.CONCLUSION An abnormally elevated serum GGT level has an important value in the diagnosis of asymptomatic choledocholithiasis secondary to cholecystolithiasis.The combination of serum GGT and ALP has better diagnostic performance. As a convenient, rapid and inexpensive test, it should be applied in secondary asymptomatic choledocholithiasis routine screening.

3D-QSAR and Surflex Docking Studies of a Series of Alkaline Phosphatase Inhibitors

Alkaline phosphatases(APs) include the placental AP(PLAP), germ cell AP(GCAP), intestinal AP(IAP) and tissue nonspecific AP(TNAP). Over expression of TNAP in smooth muscle cells of kidney and vessels provokes the progress of such serious diseases as end-stage renal disease, idiopathic infantile arterial calcification, ankylosis, osteoarthritis and diabetes. In order to design and optimize the potent TNAP inhibitors, comparative molecular field analysis(CoMFA) and comparative molecular similarity indices analysis(CoMSIA) were used to analyze 3D structure-activity relationships(3D-QSAR) of TNAP inhibitors. The 3D-QSAR model(CoMFA with q^2 = 0.521, r^2 = 0.930; CoMSIA with q^2 = 0.529, r^2 = 0.933) had a good predictability. Surflex-dock was used to reveal the binding mode between the inhibitors and TNAP protein. CoMFA, CoMSIA and docking results provide guidance for the discovery of TNAP inhibitors. Finally, eight new compounds as potential TNAP inhibitors were designed.

Albumin-to-alkaline phosphatase ratio: A novel prognostic index of overall survival in cholangiocarcinoma patients after surgery

AIM To clarify the prognostic significance of preoperative albumin-to-alkaline phosphatase ratio(AAPR) in cholangiocarcinoma(CCA) subjects receiving surgery.METHODS In this retrospective study, we included 303 CCA patients receiving surgery without preoperative therapy between 2002 and 2014. Clinicopathological characteristics(including AAPR) were analyzed to determine predictors of postoperative overall survival and recurrence-free survival(RFS). In addition,univariate and multivariate Cox proportional hazards models were conducted,followed by application of time-dependent receiver operating curves to identify the optimal cut-off.RESULTS Univariate and multivariate analyses revealed both decreased overall survival[hazard ratio(HR): 2.88, 95%CI: 1.19-5.78] and recurrence-free survival(HR: 2.31,95%CI: 1.40–3.29) in patients with AAPR < 0.41 compared to those with AAPR ≥0.41. The optimal cut-off of AAPR was 0.41. Of the 303 subjects, 253(83.5%) had an AAPR over 0.41. The overall 1-, 3- and 5-year survival rates were 70.2%, 38.0% and 16.5%, respectively in the low(< 0.41) AAPR group, which were significantly lower than those in the high(≥ 0.41) AAPR group(81.7%, 53.9%, and 33.4%,respectively)(P < 0.0001). Large tumor size, multiple tumors, and advanced clinical stage were also identified as significant predictors of poor prognosis.CONCLUSION Our outcomes showed that AAPR was a potential valuable prognostic indicator in CCA patients undergoing surgery, which should be further confirmed by prospective studies. Moreover, it is necessary to investigate the mechanisms concerning the correlation of low AAPR with poor post-operative survival in CCA patients.