Tumor-free Survival Rate Of Patients Research Articles

Study on the mechanism of liver cancer immune escape mediated by MINDY1 through regulation of PD-L1 ubiquitination level.

The novel deubiquitinase enzyme, motif interacting with ubiquitin-containing novel DUB family-1 (MINDY1), is highly expressed in liver cancer tissues and plays a crucial role in maintaining the stemness of liver cancer cells. Programmed death ligand-1 (PD-L1) is an immunosuppressive molecule overexpressed by tumour cells. The potential role of MINDY1 in inhibiting the stemness of liver cancer cells by deubiquitinating PD-L1 has not yet been reported. To investigate the mechanism by which MINDY1 mediates immune escape in liver cancer through the regulation of PD-L1 ubiquitination, we examined the expression levels of MINDY1 and PD-L1 in liver cancer and adjacent tissues from 50 hepatocellular carcinoma (HCC) patients using protein imprinting and immunohistochemistry. We analyzed the relationship between the expression levels of MINDY1 and PD-L1 in liver cancer tissues and their correlation with the 5-year tumor-free survival rates of patients. Subsequently, MINDY1 expression was knocked down in Huh7 cells using small interfering RNA (siRNA) interference or upregulated through transfection with a MINDY1 overexpression plasmid. The effects of MINDY1 knockdown or overexpression on the proliferation, apoptosis, migration, and invasion of HCC cells, as well as the regulation of PD-L1 binding and ubiquitination, were assessed. The 5-year tumor-free survival rates were significantly lower in both the high MINDY1 expression group and the high PD-L1 expression group (χ2 = 4.919 and 13.158, respectively).A significant difference in survival was observed between the high and low MINDY1 expression groups (χ2= 27.415). MINDY1 was found to directly interact with PD-L1, with MINDY1 gene knockdown promoting PD-L1 ubiquitination and MINDY1 overexpression inhibiting PD-L1 ubiquitination. All comparisons yielded statistically significant results (P < 0.05). In conclusion, MINDY1 inhibits the malignant progression of liver cancer by inhibiting PD-L1 ubiquitination and mediating immune escape.

Feasibility of novel intraoperative navigation for anatomical liver resection using real-time virtual sonography combined with indocyanine green fluorescent imaging technology.

To analyze the feasibility and clinical effect of novel intraoperative navigation of real-time virtual sonography (RVS) combined with indocyanine green (ICG) fluorescent imaging technology in anatomical liver resection (ALR) for hepatocellular carcinoma. The clinical data of 41 patients who underwent ALR using RVS intraoperative navigation combined with ICG fluorescent imaging technology in the Department of Hepatobiliary Surgery of Peking University International Hospital from January 2020 to May 2022 were retrospectively analyzed. RVS was applied to guide the surgical plane through fusing real-time intraoperative ultrasound images with corresponding preoperative CT or MRI images. Operation methods, operation time, intraoperative blood loss, operative margin, hospital stay and postoperative complications were analyzed. The 1-year overall survival rate and tumor-free survival rate of patients were followed up by outpatient review or telephone calls. ALR surgery was performed on each of 41 patients. There were no deaths during perioperative period and postoperative complications occurred in 7 cases (17.1%). The postoperative pathological examinations demonstrated all cases of hepatocellular carcinoma and negative operative margins. The 41 patients were followed up for 12 to 20 months, with a median follow-up time of 14 months. The overall survival rate 1 year after surgery was 100.0% (41/41), 3 patients (7.3%) experienced tumor recurrence, and the tumor-free survival rate of 1 year after surgery was 92.7% (38/41). In conclusion, novel intraoperative navigation of RVS combined with ICG fluorescent imaging technology is safe and feasible in anatomical segmental hepatectomy of hepatocellular carcinoma.

Risk factors and prediction model of level II lymph node metastasis in papillary thyroid carcinoma.

Surgical management of lateral lymph nodes in papillary thyroid carcinoma, especially at level II, remains controversial. This study aimed to investigate the risk factors for level II lymph node metastasis in patients with papillary thyroid carcinoma and establish a prediction model to estimate the metastatic risk. A total of 768 patients with papillary thyroid carcinoma underwent thyroidectomy and central plus lateral lymph node dissection, including levels VI, II, III, and IV, at the First Affiliated Hospital of Chongqing Medical University from January 2016 to December 2018. Data on the clinicopathological characteristics were collected and analyzed. Univariate and multivariate analyses were performed to identify risk factors for level II lymph node metastasis. Subsequently, a predictive model was established based on the results of the multivariate analyses. The level II lymph node metastatic rate was 34.11% with the following features: largest tumor diameter >20 mm (Odds ratio=1.629, P=0.026), located in the upper pole (Odds ratio=4.970, P<0.001), clinical lymph node-positive (clinical central lymph node-positive: Odds ratio=1.797; clinical lateral lymph node-positive: Odds ratio=1.805, P=0.008), vascular invasion (Odds ratio=6.759, P=0.012), and rate of central lymph node metastasis (Odds ratio=2.498, P<0.001). Level III lymph node metastasis (Odds ratio=2.749, P<0.001) and level IV lymph node metastasis (Odds ratio=1.732, P=0.007) were independent of level II lymph node metastasis predictors. The prediction model's areas under the receiver operating characteristic curve were 0.815 and 0.804, based on bootstrapping validation. Level II lymph node metastasis was associated with the tumor-free survival rate of patients with papillary thyroid carcinoma (P<0.001). Largest tumor diameter >20 mm, located in the upper pole, clinical lymph node-positive, vascular invasion, rate of central lymph node metastasis, and levels III and IV lymph node metastases were independent level II lymph node metastasis predictors. We developed a prediction model for level II lymph node metastasis. Overall, level II lymph node metastasis dissection should be individualized according to clinicopathological data both preoperatively and intraoperatively.

Sphingomyelin Phodiesterase Acid-Like 3A Promotes Hepatocellular Carcinoma Growth Through the Enhancer of Rudimentary Homolog.

BackgroundHepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with unclear pathogenesis. Sphingomyelin phodiesterase acid-like 3A (SMPDL3A) affects cell differentiation and participates in immune regulation. However, its molecular biological function in HCC has not yet been elucidated.MethodsData from 180 HCC patients were analyzed the relationship between the expression of SMPDL3A in liver cancer tissues and the prognosis of liver cancer patients. Crispr-Cas9 dual vector lentivirus was used to knock out SMPDL3A in HCC cell lines. The effects of SMPDL3A on cell viability were determined by CCK8 assay, clone formation experiment, cell cycle assay, cell scratch, TUNEL experiment and flow cytometry. Xenograft tumor assays in BALB/c nude mice confirmed that SMPDL3A promoted tumor growth and in vivo. Preliminary exploration of SMPDL3A interacting protein by mass spectrometry analysis and co-immunoprecipitation.ResultsThis study showed that the expression of SMPDL3A in HCC tissue differed from that in tumor-adjacent tissues. Moreover, the overall survival rate and tumor-free survival rate of patients with high-SMPDL3A expression were significantly lower than those with low-SMPDL3A expression. SMPDL3A expression was closely related to the level of protein induced by PIVKA-II, liver cirrhosis, tumor diameter, microvascular invasion, and Barcelona clinic liver cancer staging. Thus, SMPDL3A is an independent risk factor that affects the tumor-free survival rate and overall survival rate of HCC patients. In vitro study using Crispr-Cas9 genome editing technology revealed the knockout effect of SMPDL3A on cell proliferation, apoptosis, and migration. Cell counting kit-8 assay and clone formation experiment showed that sgSMPDL3A inhibited tumor cell proliferation and migration. Flow cytometry and TUNEL assay showed that sgSMPDL3A promoted apoptosis in tumors. Moreover, sgSMPDL3A inhibited tumor growth during subcutaneous tumor formation in nude mice. Immunohistochemistry of Ki67 and PNCA also indicated that sgSMPDL3A inhibited subcutaneous tumor proliferation in tumor-bearing nude mice. Further experiments showed that SMPDL3A interacts with the enhancer of rudimentary homolog (ERH).ConclusionsHigh-SMPDL3A expression was related to poor prognosis of patients with HCC. Knockout of SMPDL3A inhibited the proliferation and migration and accelerated the migration of HCC cells. SMPDL3A interacted with ERH to affect the tumorigenesis and progression of HCC.

High expression of the transcriptional coactivator TAZ is associated with a worse prognosis and affects cell proliferation in patients with medulloblastoma.

The transcriptional coactivator tafazzin (TAZ) serves pivotal roles in organ development, tumor initiation and tumor progression. However, to the best of our knowledge, the expression of TAZ and its clinical significance in human medulloblastoma have not been defined. The present study aimed to clarify the clinical and biological significance of TAZ expression in human medulloblastoma. Immunohistochemical staining for TAZ was performed with 72 medulloblastoma and three normal brain tissue samples. A high expression level of TAZ was detected in 65.28% of medulloblastoma tissues, whereas low expression was identified in the normal brain tissues. TAZ expression was significantly associated with medulloblastoma recurrence. However, the expression of TAZ was not associated with sex, age, tumor location, tumor maximal diameter and tumor histology. Furthermore, both the overall survival and tumor-free survival rate of patients with high levels of expression of TAZ were shorter compared with those of patients with tumors expressing low levels of TAZ. In univariate and multivariate Cox regression analyses, TAZ expression was identified as a significant prognostic factor for patients with medulloblastoma. Functionally, downregulation of TAZ inhibited the proliferation and tumor formation of medulloblastoma cells and the expression of cell-cycle associated proteins in Daoy cells. In conclusion, high expression of TAZ may serve as a prognostic marker for patients with medulloblastoma and TAZ may be a potential target for medulloblastoma therapy.

Association between expression of Cullin 4B and prognosis of patients after liver transplantation

Objective To investigate the effect of expression of Cullin 4B (CUL4B) on the prognosis of patients after liver transplantation for hepatocellular carcinoma (HCC). Methods The retrospective case-control study was conducted. The clinicopathological data of 79 patients who underwent liver transplantation for HCC in the First Affiliated Hospital of Sun Yat-sen University between January 1, 2014 and June 30, 2015 were collected. The specimens of HCC tissues were collected and embedded in paraffin, and then were detected by immunohistochemistry staining. Observation indicators: (1) expression of CUL4B in HCC tissues; (2) follow-up and survival; (3) prognostic factors analysis after liver transplantation; (4) association between expression of CUL4B and recurrence and metastasis of tumor after liver transplantation. Follow-up using outpatient examination and telephone interview was performed to detect tumor recurrence or metastasis and survival up to June 2018. Measurement data with normal distribution were represented as ±s. The comparison between groups of count data was done using the chi-square test. The survival curve drawn using the Kaplan-Meier method, and the survival analysis was done by Log-rank test. The univariate and multivariate analysis were respectively done using the COX regression model. The association analysis was done using the Pearson test. Results (1) Expression of CUL4B in HCC tissues: immunohistochemistry staining showed that CUL4B was mainly expressed in the cytoplasm, with a powerful brownish-yellow staining. The high expression and low expression of CUL4B in HCC tissues were detected in 64 and 15 patients, respectively. (2) Follow-up and survival: 79 patients were followed up for 38-56 months, with an average time of 46 months. During the follow-up, 37 patients had no tumor recurrence and 42 had tumor recurrence (32 with tumor extrahepatic metastasis and 10 with intrahepatic metastasis); 36 had survival and 43 died; the 1- and 3-year overall survival rates were respectively 86.84% and 63.25%, and 1- and 3-year tumor-free survival rates were respectively 62.31% and 51.27%. (3) Prognostic factors analysis after liver transplantation: ① Results of univariate analysis showed that preoperative alpha-fetoprotein (AFP), Child-Pugh score, maximum tumour dimension, capsular invasion, intravascular tumor thrombus, Edmonson pathological grading and expression of CUL4B were related factors affecting the 3-year overall survival rate of patients after liver transplantation for HCC [Hazard Ratio (HR)=2.17, 3.36, 3.66, 2.43, 2.19, 3.36, 2.84, 95% confidence interval (CI): 1.17-4.04, 1.53-7.42, 2.10-6.42, 1.33-4.17, 1.08-9.04, 1.58-7.59, 1.17-6.32, P<0.05]. The preoperative alpha-fetoprotein (AFP), Child-Pugh score, maximum tumour dimension, capsular invasion, intravascular tumor thrombus, Edmonson pathological grading and expression of CUL4B were related factors affecting the 3-year tumor-free survival rate of patients after liver transplantation for HCC (HR=2.06, 3.72, 3.16, 2.36, 2.83, 3.21, 1.69, 95%CI: 1.34-4.85, 1.72-8.63, 1.79-7.31, 1.46-4.86, 1.19-8.63, 1.19-7.92, 1.06-4.87, P<0.05). ② Results of multivariate analysis showed that maximum tumour dimension, intravascular tumor thrombus and expression of CUL4B were independent factors affecting the 3-year overall survival rate of patients after liver transplantation for HCC [Odds ratio(OR)=3.43, 3.69, 2.81, 95%CI: 1.16-6.02, 1.96-9.38, 1.04-9.63, P<0.05]. The maximum tumour dimension, intravascular tumor thrombus and expression of CUL4B were independent factors affecting the 3-year tumor-free survival rate of patients after liver transplantation for HCC (OR=2.25, 4.72, 2.74, 95%CI: 1.16-4.02, 1.98-9.47, 1.03-7.10, P<0.05). The 3-year overall survival rate in patients with high- and low-expressions of CUL4B was respectively 66.7% and 32.8%, with a statistically significant difference (χ2=5.69, P<0.05). The 3-year tumor-free survival rate in patients with high- and low-expressions of CUL4B was respectively 73.3% and 18.6%, with a statistically significant difference (χ2=4.63, P<0.05). (4) Association between expression of CUL4B and recurrence and metastasis of tumor after liver transplantation: results of Pearson test showed that expression of CUL4B was significantly associated with HCC recurrence and metastasis after liver transplantation (r=0.62, P<0.05). The further analysis showed that expression of CUL4B was significantly associated with extrahepatic metastasis after liver transplantation (r=0.84, P<0.05). Conclusion The expression of CUL4B is associated with HCC recurrence after liver transplantation, and it can be as a predictor for HCC recurrence and distant metastasis after liver transplantation. Key words: Hepatic neoplasms; Liver transplantation; Cullin 4B; Recurrence; Metastasis; Prognosis

Prognostic significance of tumor-infiltrating mast cells in colorectal cancer patients

Objective To investigate the relationship between tumor-infiltrating mast cell (TIM) and the clinicopathological and prognostic factors of patients with colorectal cancer.Methods A total of 282 cases of paraffin-embedded colorectal cancer specimens were obtained from the First Affiliated Hospital of Sun Yat-sen University from January 2002 to December 2005.The density of TIM was determined by immunohistochemical staining.According to the mean TIM density detected [ ( 8.4 + 6.5 )/HPF ],all the patients were divided into low-TIM density group (mean TIM density ＜8.4/HPF) and high-TIM density group (mean TIM density ＞8.4/HPF).The clinicopathological factors and the prognosis of patients between high-TIM density group and low-TIM density group were compared.All data were analyzed using the t test or chi-square test.The survival curve was drawn using the Kaplan-Meier method,and the survival of the patients was analyzed by the Log-rank test.The clinicopathological factors were analyzed retrospectively with the univariate and multivariate COX regression model.Results TIM was detected in all the patients with colorectal cancer.Significant differences were observed in the number of patients in N stage and TNM stage between patients in the high-TIM density group and those in the lowTIM density group (x2 =6.025,7.410,P ＜ 0.05 ).All patients were followed up till September 2010,the 5-year overall and tumor-free survival rates of patients were 82.9％ and 63.1％ in the low-TIM density group,79.0％ and 59.3％ in the high-TIM density group,with significant difference between the 2 groups (P ＜ 0.05 ).COX proportional hazard regression model revealed that high density of TIM was associated with short overall survival time and tumor-free survival time of colorectal cancer patients ( RR =2.119,95 ％ CI 1.326- 3.386; RR =2.084,95 ％ CI 1.357-3.199,P ＜0.05).The resuhs of multivariate analysis showed that high density of TIM was the independent factor influencing the overall survival time and tumor-free survival time (RR =1.651,95％ CI 1.009-2.702; RR =1.680,95％ CI 1.074-2.629,P ＜ 0.05 ).Conclusion High density of TIM is correlated with the N stage and TNM stage of colorectal cancer,and it is an independent predictor of poor survival for patients with colorectal cancer. Key words: Colorectal neoplasms; Tumor-infiltrating mast cell; Prognosis

Clinicopathological factors on the prognosis of patients with stage lII colorectal cancer

Objective To analyze the clinicopathological factors on the prognosis and investigate the necessity of adjuvant chemotherapy for patients with stage Ⅱ colorectal cancer.Methods The clinical data of 255 patients with stage Ⅱ colorectal cancer who were admitted to the First Affiliated Hospital of Sun Yat-Sen University from January 2000 to December 2005 were collected.The survival curve was drawn by Kaplan-Meier method,and the survival rate of the patients were analyzed by Log-rank test.Factors influencing the survival were analyzed by Cox regression model.Results All patients were followed up till April 23,2010,and the mean time of follow-up was (63 ± 22)months.The median survival time was 63 months.The 5-year and tumor-free survival rates were 85.3％ and 83.7％,respectively.The 5-year overall and tumor-free survival rates of patients without preoperative bowel obstruction or perforation were 86.9％ and 85.6％,which were sigaificantly higher than 72.7％and 68.4％ of patients with preoperative bowel obstruction or perforation(x2 =4.546,4.573,P ＜ 0.05 ).The 5-year overall and tumor-free survival rates of patients with negative resection margin were 85.5％ and 83.9％,which were significantly higher than 75.0％ and 75.0％ of patients with positive resection margin(x2 =7.020,6.009,P ＜ 0.05 ).The result of multivariate analysis revealed that preoperative bowel obstruction or perforation were the independent risk factors for patients with stage Ⅱ colorectal cancer(Wald =4.477,relative risk =2.371,95 ％ confidence interval:1.066-5.275,P ＜ 0.05 ).The 5-year overall and tumor-free survival rates were 87.3％ and 86.0％ for patients who received adjuvant chemotherapy,and were 82.2％ and 80.3％ for patients who did not receive adjuvant chemotherapy (P ＞ 0.05 ).Conclusions Preoperative bowel obstruction or perforation are independent risk factors for the survival of patients with stage Ⅱ colorectal cancer.Adjuvant chemotherapy could not improve the prognosis of patients with stage Ⅱ colorectal cancer. Key words: Colorectal neoplasms; Stage Ⅱ ; Prognosis; Adjuvant chemotherapy; High-risk factor

Prognostic value of the content of lentil lectin-rcactive alpha-fetoprotein-L3 in early-stage hepatocellular carcinoma

Objective To explore the prognostic value of the content of lentil lectin-reactive alphafetoprotein-L3(AFP-L3)in early-stage hepatocellular carcinoma(HCC).Methods According to the content of alpha.fetoprotein(AFP)and AFP-L3 before the treatment,97 patients with early-stage HCC were divided into group A(AFP＞20 μg/L & AFP-L3＜15%,n=29),group B(15%≤AFP-13≤50% & 20 μg/L≤AFP≤200 μg/L,n=16),group C(AFP-13＞50%& AFP＞200 μg/L,n=13),group D(AFP-L3＞50% & 20 μg/L≤AFP≤200 μg/L,n=24)and group E(15%≤AFP-L3≤50%& AFP＞200 μg/L,n=15).The degree of tumor differentiation,the 1-,2-,3-year survival rates and tumor-free survival rates of the patients were analyzed.Results The degree of tumor differentiation.3-year survival rate and tumor-free survival rate of patients in group A were significantly higher than those in the other 4 groups(χ2=21.051,10.043,4.450,6.977,25.566,P＜0.05).The degree of tumor differentiation,1-,2-,3-year survival rates and tumor-free survival rates of the patients in group C and D were significantly lower than those in other 3 groups(χ2=7.938,3.488,9.085.P＜0.05).Conclusions The increase of AFP-L3 content is closely related to poorly differentiated HCC and bad prognosis.especially when the AFP Ievel is low.The detection of AFP-L3 content before and after operation is beneficial to the evaluation of the prognosis of HCC patients. Key words: Liver neoplasms; Lentil leetin-reactive alpha-fetoprotein-L3; Prognosis

Skull Base Surgery for Malignancy: Implications of Dural and Brain Invasion

In the not too distant past, patients with intracranial invasion of malignant tumors originating in the upper aerodigestive tract that invaded the dura and especially the brain were considered inoperable and incurable. Experience over time has shown the pathophysiology of the intracranial spread of these malignancies and has revealed that although the prognosis is worse with tumor spread to dura and/or brain, the 5-year tumor-free survival is reasonable. The current study covers a review of all the patients operated upon at a single institution (The University of California Davis-Center for Skull Base Surgery) over a period of 30 years comparing the 2- and 5-year tumor-free survival rate of patients with malignancies of the upper aerodigestive tract that had invaded dura or brain with those who had no such involvement. During this period, 181 patients had skull base surgery for head and neck tumors. There were 36 benign tumors and 145 malignancies. The 2-year tumor-free survival for the malignancies was 41.6% with dural invasion and 50% without. The 5-year survival rate was 35.4% with dural invasion and 54% without. There were 22 patients who had brain invasion who were operated on for cure and followed for 2 years. The tumor-free survival rate was 31.8% and the 5-year survival rate for the 20 cases operated on with curative intent was 30%.