OBJECTIVE: To explore the expression of perforin and granzyme-B in peripheral blood lymphocyte (PBL) in patients with prostate cancer (PCa) and the clinical significance. METHODS: The expressions of perforin and granzyme-B in PBL were detected by fluorescence quantitative reverse transcription polymerase chain reaction. The results of perforin and granzyme-B expression were compared among patients with PCa (n=60), patients with BPH (benign prostatic hyperplasia, n=40) and healthy controls (n=20). RESULTS: Th e expressions of perforin and granzyme-B in patients with PCa were significantly lower than that in patients with BPH or that in the healthy controls (P<0.05), respectively. Furthermore, in PCa patients with low pathological grade, the expressions of perforin and granzyme-B in PBL was statistically higher than that in patients with high pathological grade (P<0.05). The expressions of perforin and granzyme-B in PCa patients at high clinical stage was statistically lower than that in PCa patients at low clinical stage (P<0.05). CONCLUSION The results of this study suggest that development and progression of PCa might be associated with poor immune status of patients.
Case-Control Studies ; Granzymes ; metabolism ; Humans ; Lymphocytes ; enzymology ; Male ; Perforin ; metabolism ; Prostatic Hyperplasia ; Prostatic Neoplasms ; immunology

Objective:To evaluate the efficacy of first-line tyrosine kinase inhibitors (TKI) plus immune checkpoint inhibitors (ICI) in metastatic fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC).Methods:The data of 87 metastatic FH-deficient RCC patients from West China Hospital ( n=44), Renji Hospital ( n=27) and Sun Yat-sen University Cancer Center (n=16) from Mar 2019 to Aug 2022 were retrospectively analyzed. The median age was 37(30, 47) years, the male to female ratio was 1.9∶1. The median size of tumor was 7.5(5.0, 10.0) cm. Sixty-one patients (70.1%) had germline FH mutations, and 26 patients (29.9%) had somatic FH mutations. Forty-nine patients (56.3%) metastasis disease at initial diagnosis, and 38 patients (43.7%) had metachronous metastasis. The most common site of metastasis was lymph node (41/87, 47.1%), followed by bone (33/87, 37.9%), liver (22/87, 25.3%), and lung (14/87, 16.1%). Fifteen patients (17.2%) had weak expression of FH protein and 59 patients (67.8%) had positive PD-L1 expression. The most common treatments were sintilimab plus axitinib (52/87, 59.8%), followed by pembrolizumab plus cabozantinib (7/87, 8.0%), tirelizumab plus axitinib (6/87, 6.9%), pembrolizumab plus axitinib (5/87, 5.7%), and toripalimab plus axitinib (4/87, 4.6%). Thirteen patients (13/87, 14.9%) received other ICI plus TKI combination treatments. Statistical analysis was conducted using R 4.2.3 software. Kaplan Meier survival curve was used to evaluate survival data, and log-rank test was used to compare differences between treatment groups. Results:The overall objective response rate (ORR) and disease control rate (DCR) of first-line TKI + ICI were 39.1% and 89.7%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 16.5 months and 71.0 months, respectively. For first-line sintilimab plus axitinib, the ORR and DCR were 44.2% and 92.3%, respectively. The median PFS was 17.3 months and the median OS was not reached for this combination treatment. The efficacy of first-line tirelizumab plus axitinib was inferior to other treatment strategies (median PFS: 4.0 vs. 16.6 months, P<0.001; median OS: 22.0 vs. 71.0 months, P=0.043). Subgroup analyses further showed that the efficacy of ICI+ TKI combination therapy was consistent in patients with different clinicopathologic and genomic features. However, patients with liver metastasis had shorter OS than those without liver metastasis (median OS: 26.3 vs. 71.0 months, P=0.021). Conclusion:First-line TKI + ICI is effective for metastatic FH-deficient RCC and can significantly prolong the survival of the patients.

Objective:To evaluate the efficacy and safety of Tyrosine Kinase Inhibitors (TKIs) combined with stereotactic body radiation therapy(SBRT) in the treatment of renal cell carcinoma (RCC) patients with bone metastasis.Methods:The clinical data of 80 RCC patients with bone metastasis in Sun Yat-sen University Cancer Center from April 2010 to April 2020 were analyzed retrospectively. Among them, 64 patients were medium or high risk according to the International Metastatic Renal Cell Carcinoma Database Consortium(IMDC) score. Twenty-four patients received TKI therapy alone(Group A), and the other 56 cases received TKIs combined with SBRT to bone metastastic lesions (Group B).Results:The median follow-up period was 20.7 months (4.8-115.6 months), 70 patients received second or third-line targeted drug therapy, and 4 patients in group A and 15 patients in group B received TKI plus immunotherapy. Fifty-four patients had symptoms of bone pain before radiotherapy, 46 patients were satisfied with the analgesic effect after SBRT treatment. Twelve patients got complete response (CR) after bone lesions, and 32 patients achieved partial response (PR). Forty patients died of disease progression during follow-up. The median OS was: 20.7 months vs not reached(Group A vs. Group B), and the 2-y OS and 5-y OS were 50% vs. 62%, and 19% vs. 56%, respectively ( P=0.006). There were only 2 patients (3.6%) had grade 3 SBRT related adverse events. Conclusions:SBRT combined with TKIs improved the quality of life and prolonged the overall survival of RCC patients with bone metastasis.

Objective:To compare the pathological results and complications of limited and extended pelvic lymph node dissection among high-risk prostate cancer patients, and to explore the risk factors that affect the rate of lymph node metastasis in high-risk prostate cancer patients.Methods:The data of 800 high-risk prostate cancer patients who underwent radical prostatectomy and pelvic lymph node dissection from January 2016 to December 2020 in three affiliated hospital of Sun Yat-sen University were analyzed retrospectively. According to the scope of pelvic lymph node dissection, they were divided into limited pelvic lymph node dissection (LPLND) group and extended pelvic lymph node dissection (EPLND) group. There were 172 patients underwent LPLND, and 628 patients underwent EPLND.The age of the patients in the LPLND group was 67 (62, 72) years old, diagnosed PSA 20.7 (10.9, 54.8) ng/ml. The biopsy Gleason score 6 in 22 cases, 7 in 59 cases, 8 in 56 cases and 9-10 in 35 cases.The clinical T stage: T 1 in 29 cases, T 2 in 102 cases, T 3 in 37 cases, T 4 in 4 cases; N 0 in 160 cases and N 1 in 12 cases. 50 patients received neoadjuvant hormonal therapy. The age of patients in the EPLND group was 67 (63, 72) years old, diagnosed PSA was 23.9 (14.0, 46.8) ng/ml. Biopsy Gleason Score 6 in 51 cases, 7 in 194 cases, 8 in 218 cases and 9-10 in 165 cases. Clinical T stage: T 1 in 114 cases, T 2 in 341 cases, T 3 in 144 cases, T 4 in 29 cases; N 0 in 526 cases and N 1 in 102 cases.158 patients received neoadjuvant hormonal therapy. There were no significant differences in the age, PSA, puncture Gleason score, clinical T stage, and whether or not to receive neoadjuvant hormonal therapy between the two groups of patients ( P>0.05). The difference in clinical N staging was statistically significant ( P=0.002). The number of postoperative lymph nodes, positive pelvic lymph nodes and postoperative complications and other related clinical and pathological data of the two groups were analyzed. Multivariate logistic regression was used to analyze the risk factors of patients with positive lymph nodes. Results:The median number of lymph nodes harvested [13(8, 19)vs. 6(4, 13), P<0.001] and the rate of positive lymph node cases[31.2%(196/628) vs. 10.5%(18/172), P<0.001] in the EPLND group was significantly higher than those in the LPLND group. Preoperative PSA, clinical N staging, Gleason score, and way of lymph node dissection were independent risk factors for postoperative positive pelvic lymph node in high-risk prostate cancer patients. Compared with the LPLND group, the ELPND group had a higher postoperative complication rate [19.9%(125/628) vs. 11.0%(11/172), P=0.007]. Conclusions:Compared with the LPLND, EPLND in high-risk prostate cancer patients can harvest more lymph nodes and increase the detection rate of positive lymph nodes. The complications of EPLND were higher than those of LPLND. Preoperative PSA, clinical N stage, Gleason score, and the way of lymph node dissection are independent risk factors for positive pelvic lymph node dissection.