Objective:This study investigated the expression level of phosphatidylserine-specific phospholipase A1(PLA1A)in colorectal can-cer(CRC)and analyzed its correlations with clinicopathological features,prognosis,and immune infiltration.Methods:The expression level of PLA1A in CRC was screened,and the influence of this expression level on patient prognosis was analyzed using bioinformatics methods.A cohort of 192 patients diagnosed with CRC at Shanxi Province Cancer Hospital from January to December 2020 were selected.The PLA1A ex-pression level in those with CRC was determined using immunohistochemistry(IHC)and real-time quantitative reverse transcription PCR(RT-qPCR).The relationship between PLA1A level and the clinicopathological features of the patients with CRC was analyzed using the chi-square test.The expression levels of immune cell markers CD4 and CD8 as well as immunosuppressive checkpoints PD-1,TIM-3,and CTLA-4 in CRC were detected via IHC,and their correlations with PLA1A level were analyzed using the chi-square test.Results:The results of bioinformatics analysis showed that the expression level of PLA1A in CRC tissue was higher than paracancerous tissue,which correlated with overall surviv-al(OS)(P<0.05).The IHC and RT-qPCR results showed that PLA1A expression level was significantly upregulated in CRC tissiue(P<0.05).High PLA1A level was closely associated with the TNM stage,degree of differentiation,and lymph node metastasis(P<0.05).The IHC results demonstrated that PLA1A positively correlated with the infiltrating CD8+T cell level(P<0.05).In addition,the elevated PLA1A levels upregu-lated the expressions of immunosuppressive checkpoints PD-1,TIM-3,and CTLA-4(P<0.05).Conclusions:PLA1A is highly expressed in CRC,which is closely related to immune infiltrating cells and immunosuppressive checkpoints,suggesting that PLA1A plays an important role in immune infiltration in CRC,a finding that provides guidance in the treatment of CRC.

Objective:To discuss the correlation of pathologic findings after radical prostatectomy and preoperative 18F-PSMA-1007 PET/CT parameters with the prognosis of patients with prostate cancer. Methods:A retrospective case series study was conducted. The clinicopathological data of 48 patients with prostate cancer who underwent radical prostatectomy in Shanxi Province Cancer Hospital between January 2019 and August 2023 were retrospectively analyzed. All patients underwent 18F-PSMA-1007 PET/CT imaging before surgery. The age, the preoperative serum total prostate-specific antigen (tPSA), prostate-specific antigen density (PSAD), prostate volume, tumor diameter, TNM staging, the pathologic data after radical prostatectomy [International Society of Urological Pathology (ISUP) grade, resection margin status, nerve invasion], and preoperative maximum standard uptake value (SUV max) were collected. The receiver operating characteristic (ROC) curves were used to evaluate the efficacy of PET/CT parameter SUV max in predicting tumor recurrence after prostate cancer surgery. The recurrence-free survival (RFS) was analyzed by using the Kaplan-Meier method and log-rank test was performed. Cox proportional risk model was used to analyze the factors influencing RFS after radical prostatectomy. Results:All 48 patients were acinar adenocarcinoma. The median level of the patients' serum tPSA was 19.16 (10.50, 30.99) ng/ml; the median prostate volume was 36.20 (31.83, 45.48) ml; the median tumor diameter was 2.80 (1.60, 4.00) cm; the median PSAD was 0.48 (0.31,1.02) ng·ml -1·cm -3. The primary SUV max of prostate cancer was 13.61 (8.10, 20.20) . Of the 48 patients, 1 case died of heart disease and 1 case died of COVID-19 within 3 to 6 months after surgery, and the rest 46 patients were analyzed for prognosis. Among 46 cases, 26 were in the ISUP low-grade group and 20 were in the high-grade group; 17 were positive and 29 were negative for nerve invasion; 7 were positive and 39 were negative for margin status. The median follow-up time was 18.5 (8-64) months. There were 30 recurrence-free patients and 16 recurrent patients by the follow-up in April 2024. The median RFS time was 15 months; and there were statistically significant differences in RSF among the ISUP high-grade and low-grade groups, preoperative SUV max ≥ 16.77 and < 16.77 groups, positive and negative resection margin groups (all P < 0.01). SUV max was positively correlated with ISUP pathological grade and tPSA level ( r value was 0.634, 0.584, respectively; both P < 0.01). The differences in preoperative serum tPSA level, PSAD, tumor diameter, and SUV max were statistically significant between the ISUP low-grade group and the high-grade group (all P < 0.01); the differences in preoperative serum tPSA, PSAD, and tumor diameter were statistically significant between the nerve invasion positive group and nerve invasion negative group (all P < 0.01); the differences in preoperative serum tPSA, PSAD, tumor diameter, and SUV max between patients with positive resection margins or not were not statistically significant (all P > 0.05). Multivariate Cox regression analysis showed that the tumor resection margin status (negativity vs. positivity: HR = 7.82,95% CI: 1.97-31.07, P < 0.01), ISUP pathological grade (low grade vs. high grade: HR = 4.34,95% CI:1.21-15.62, P < 0.05), and the preoperative SUV max (<16.77 vs. ≥ 16.77: HR = 4.18, 95% CI:1.36-12.85 , P < 0.05) were independent influencing factors for RFS in patients with prostate cancer after radical prostatectomy. Conclusions:Pathological grading after radical prostatectomy and the preoperative 18F-PSMA-1007 PET/CT parameters are associated with the prognosis of patients with prostate cancer.

Objective:This study investigated the expression level of phosphatidylserine-specific phospholipase A1(PLA1A)in colorectal can-cer(CRC)and analyzed its correlations with clinicopathological features,prognosis,and immune infiltration.Methods:The expression level of PLA1A in CRC was screened,and the influence of this expression level on patient prognosis was analyzed using bioinformatics methods.A cohort of 192 patients diagnosed with CRC at Shanxi Province Cancer Hospital from January to December 2020 were selected.The PLA1A ex-pression level in those with CRC was determined using immunohistochemistry(IHC)and real-time quantitative reverse transcription PCR(RT-qPCR).The relationship between PLA1A level and the clinicopathological features of the patients with CRC was analyzed using the chi-square test.The expression levels of immune cell markers CD4 and CD8 as well as immunosuppressive checkpoints PD-1,TIM-3,and CTLA-4 in CRC were detected via IHC,and their correlations with PLA1A level were analyzed using the chi-square test.Results:The results of bioinformatics analysis showed that the expression level of PLA1A in CRC tissue was higher than paracancerous tissue,which correlated with overall surviv-al(OS)(P<0.05).The IHC and RT-qPCR results showed that PLA1A expression level was significantly upregulated in CRC tissiue(P<0.05).High PLA1A level was closely associated with the TNM stage,degree of differentiation,and lymph node metastasis(P<0.05).The IHC results demonstrated that PLA1A positively correlated with the infiltrating CD8+T cell level(P<0.05).In addition,the elevated PLA1A levels upregu-lated the expressions of immunosuppressive checkpoints PD-1,TIM-3,and CTLA-4(P<0.05).Conclusions:PLA1A is highly expressed in CRC,which is closely related to immune infiltrating cells and immunosuppressive checkpoints,suggesting that PLA1A plays an important role in immune infiltration in CRC,a finding that provides guidance in the treatment of CRC.

Objective:To discuss the correlation of pathologic findings after radical prostatectomy and preoperative 18F-PSMA-1007 PET/CT parameters with the prognosis of patients with prostate cancer. Methods:A retrospective case series study was conducted. The clinicopathological data of 48 patients with prostate cancer who underwent radical prostatectomy in Shanxi Province Cancer Hospital between January 2019 and August 2023 were retrospectively analyzed. All patients underwent 18F-PSMA-1007 PET/CT imaging before surgery. The age, the preoperative serum total prostate-specific antigen (tPSA), prostate-specific antigen density (PSAD), prostate volume, tumor diameter, TNM staging, the pathologic data after radical prostatectomy [International Society of Urological Pathology (ISUP) grade, resection margin status, nerve invasion], and preoperative maximum standard uptake value (SUV max) were collected. The receiver operating characteristic (ROC) curves were used to evaluate the efficacy of PET/CT parameter SUV max in predicting tumor recurrence after prostate cancer surgery. The recurrence-free survival (RFS) was analyzed by using the Kaplan-Meier method and log-rank test was performed. Cox proportional risk model was used to analyze the factors influencing RFS after radical prostatectomy. Results:All 48 patients were acinar adenocarcinoma. The median level of the patients' serum tPSA was 19.16 (10.50, 30.99) ng/ml; the median prostate volume was 36.20 (31.83, 45.48) ml; the median tumor diameter was 2.80 (1.60, 4.00) cm; the median PSAD was 0.48 (0.31,1.02) ng·ml -1·cm -3. The primary SUV max of prostate cancer was 13.61 (8.10, 20.20) . Of the 48 patients, 1 case died of heart disease and 1 case died of COVID-19 within 3 to 6 months after surgery, and the rest 46 patients were analyzed for prognosis. Among 46 cases, 26 were in the ISUP low-grade group and 20 were in the high-grade group; 17 were positive and 29 were negative for nerve invasion; 7 were positive and 39 were negative for margin status. The median follow-up time was 18.5 (8-64) months. There were 30 recurrence-free patients and 16 recurrent patients by the follow-up in April 2024. The median RFS time was 15 months; and there were statistically significant differences in RSF among the ISUP high-grade and low-grade groups, preoperative SUV max ≥ 16.77 and < 16.77 groups, positive and negative resection margin groups (all P < 0.01). SUV max was positively correlated with ISUP pathological grade and tPSA level ( r value was 0.634, 0.584, respectively; both P < 0.01). The differences in preoperative serum tPSA level, PSAD, tumor diameter, and SUV max were statistically significant between the ISUP low-grade group and the high-grade group (all P < 0.01); the differences in preoperative serum tPSA, PSAD, and tumor diameter were statistically significant between the nerve invasion positive group and nerve invasion negative group (all P < 0.01); the differences in preoperative serum tPSA, PSAD, tumor diameter, and SUV max between patients with positive resection margins or not were not statistically significant (all P > 0.05). Multivariate Cox regression analysis showed that the tumor resection margin status (negativity vs. positivity: HR = 7.82,95% CI: 1.97-31.07, P < 0.01), ISUP pathological grade (low grade vs. high grade: HR = 4.34,95% CI:1.21-15.62, P < 0.05), and the preoperative SUV max (<16.77 vs. ≥ 16.77: HR = 4.18, 95% CI:1.36-12.85 , P < 0.05) were independent influencing factors for RFS in patients with prostate cancer after radical prostatectomy. Conclusions:Pathological grading after radical prostatectomy and the preoperative 18F-PSMA-1007 PET/CT parameters are associated with the prognosis of patients with prostate cancer.

Objective:To investigate the biological characteristics of triple negative breast cancer (TNBC) with low expression of HER2 (HER2-low).Methods:A total of 93 TNBC cases in Shanxi Cancer Hospital from 2017 to 2019 were collected and divided into HER2-negative and HER2-low groups according to HER2 expression status. The clinicopathological features and prognostic differences between the two groups were retrospectively analyzed and compared, and genetic detection of tumor tissues was performed to clarify somatic mutation status and differences between the two groups.Results:Ninety-three patients aged 26 to 86 years were enrolled, including 60 patients in the HER2-negative group and 33 patients in the HER2-low group. The distribution of HER2-low in luminal androgen receptor (LAR) subtype (14/23, 60.87%) and non-LAR subtype (19/70, 27.14%) was significantly different ( P=0.005). There were no significant differences in age, pT stage, histological grade, infiltration mode, lymph node metastasis and survival analysis. The expression of HER2-low in the tumor was heterogeneous, including different proportions of weak, weak to moderate intensity, and incomplete to intact membrane staining. With the change of the proportion of HER2-positive cells, the different distribution of those cells in the total tumor cells was noted, including cluster, mosaic and scattered patterns. The concentration and quality of DNA extracted from 71 of the 93 samples met the requirements for making libraries, including 43 in the HER2-negative group and 28 in the HER2-low group. Genetic mutations were mainly missense mutations, single nucleotide mutations, and point mutations in which base C was replaced by base T. There was no significant difference in genes with mutation frequency>3 times between the two groups. CTNNB1 and FGFR3 genes were only mutated in HER2-low group; while ALK, CYP2D6 and FAT1 genes were only mutated in HER2-negative group. HER2-low group included 18 HER2 1+ cases and 10 HER2 2+ cases. Genes with mutation frequency>3 times between the two groups included PIK3CA, TP53, SLX4, ATM and BRCA1. The mutation frequency of PIK3CA in HER2 2+ was significantly higher than that in HER2 1+ group ( P<0.05), and SLX4 gene was only mutated in HER2 1+ group. Conclusions:There are some differences of histological morphology and genetic variation between HER2-negative group and HER2-low group, and also differences in genetic variation between HER2 1+ and HER2 2+ in HER2-low group, which are helpful for more accurate stratification of TNBC and useful for finding the therapeutic target and precise treatment of HER2-low TNBC.

Purpose To evaluate the classification criteria of triple negative breast cancer(TNBC)based on histomorphol-ogy and immunohistochemistry(IHC),and to provide theoreti-cal basis for the classification and treatment of TNBCs.Methods TNBC subtyping was performed according to the histomorphologi-cal characteristics and the expression of immune markers AR,CD8 and FOXC1,and the clinicopathological features and prog-nostic differences were compared.Results Among 93 cases of TNBC,there were 23 cases(24.7％)of luminal androgen re-ceptor subtypes,24 cases(25.8％)of immunomodulatory type,39 cases(42.0％)of basal immunosuppressive type,and 7 ca-ses(7.5％)of mesenchymal type.There were significant differ-ences in the clinicopathological features of subtypes,including pT stage(P=0.030),histological grade(P＜0.001),intersti-tial lymphocyte infiltration pattern(P＜0.001),expression of PD-L1(P＜0.001),and HER2-low(P=0.024).There was no significant difference in disease-free survival among the sub-types(P＞0.05).Univariate survival analysis showed there was significant difference in disease-free survival among the subtypes at pT1 stage(P=0.011),and other clinicopathological features were not independent prognostic factors.Conclusion The clini-copathological characteristics of TNBC subtypes are different,which are expected to be an alternative choice for complex gene expression profile analysis and to provide theoretical basis for subtypic therapy and targeted therapy.

Objective:To investigate the morphological and biological characteristics of polyploid tumor giant cells (PGCC) produced by ovarian cancer cell line SKOV3 induced by CoCl 2. Methods:Human ovarian cancer cell line SKOV3 was induced-cultured with 300 μmol/L CoCl 2 in the simulated hypoxic environment for 36 h, the live cells continued to be conventionally cultured and passaged, and the cells collected 20 days later were PGCC group; SKOV3 cell line cultured conventionally was the control group. The formation process and morphological characteristics of PGCC were observed by inverted microscope. The expression of tumor stem cell markers OCT4 and CD117 were detected by immunocytochemistry. The adipogenic differentiation and osteogenic differentiation potential of PGCC were detected by using human bone marrow mesenchymal stem cell adipogenic differentiation assay kit and human bone marrow mesenchymal stem cell osteogenic differentiation assay kit.The cell migration ability of PGCC was detected by scratch assay. PGCC group and control group SKOV3 cells were treated with 1 μmol/L paclitaxel, and the cell morphology of the two groups was observed by microscope at 0, 24 and 48 h to detect the resistance of PGCC to chemotherapy drugs. Results:A small amount of PGCC was observed in SKOV3 cell line cultured in conventional medium under the microscope. CoCl 2 can induce SKOV3 cells to form PGCC, which was nearly round in shape and lacked branching. Its volume was 3 times or more than that of SKOV3 cells, and the nuclei were usually megakaryons or multinucleates, PGCC can produce daughter cells by budding. Immunocytochemical staining showed that OCT4 was positive in some PGCC, but no CD117 was positive. Neither OCT4 nor CD117 was expressed in SKOV3 cells. When cultured with lipid-induced differentiation medium of human bone marrow mesenchymal stem cells, the formation of large vacuoles in the cytoplasm of PGCC was observed at the 3rd cycle, and orange-red, round-like lipid droplets were shown by oil red O staining. Human bone marrow mesenchymal stem cells were cultured in osteogenic induction culture medium for 20 days, and alizarin red staining showed that calcium nodules formed significantly in cells of PGCC group compared with the control group. The cell scratch assay results showed that the migration rates of PGCC cultured in serum-free medium [(59±1)%, (66±3)%] were higher than those of the control group [(11±3)%, (14±5)%] at 24 and 48 h after scratch ( t values were 32.20 and 19.55, both P < 0.001). The migration rates of PGCC cultured in 10% serum medium [(92±3)%, (100±0)%] were higher than those of the control group [(20±6)%, (59±9)%] ( t values were 16.19 and 8.00, both P < 0.001). After 1 μmol/L paclitaxel treatment for 48 h, most of the cells in the PGCC group still survived, while most of the SKOV3 cells in the control group died. Conclusions:PGCC produces daughter cells by budding. PGCC has the characteristics of tumor stem cells: it expresses tumor stem cell markers and has the potential for multidirectional differentiation and strong resistance to chemotherapy drugs.

Objective:To explore the relationship between integrin ɑ3(ITGA3)expression and immune cell infiltration in colorectal cancer(CRC).Methods:Bioinformatic methods were used to analyze ITGA3 mRNA expression in pan-cancer and CRC tissues,as well as its associ-ation with CRC prognosis.The correlation between ITGA3 and tumor-infiltrating immune cells was also investigated.In total,233 cases of CRC diagnosed at Shanxi Provincial Cancer Hospital between January and December 2021 were included,and ITGA3,CD8,CD163,FOXP3,PD-L1,CTLA-4,and PD-1 expression in CRC tissues were determined by immunohistochemistry(IHC)to analyze the relationship between ITGA3 and infiltrating immune cells and immune checkpoints.Results:Bioinformatics analysis showed elevated ITGA3 mRNA levels in CRC.High ITGA3 expression was associated with PFS(P＜0.05).Univariate and multifactorial analyses showed that age and stage were significantly cor-related with prognosis(P＜0.05).In addition,ITGA3 upregulation was closely correlated with multiple immune cell infiltration levels in CRC.Furthermore,IHC results showed that ITGA3 expression in CRC tissues was significantly higher than that in adjacent normal tissues(P＜0.05).ITGA3 expression was associated with lymph node metastasis(P＜0.05)and correlated with the expression of immune markers,such as CD8+T-cells,PD-L1,and CTLA-4(P＜0.05).Conclusions:ITGA3 is highly expressed in CRC,which is closely related to immune cell infiltration and may regulate the tumor immune microenvironment,which provides a new idea for clinical treatment and a potential new independent predictive marker.

Objective:To investigate the correlation between KRAS, NRAS and BRAF V600E gene mutations and the clinicopathological characteristics of patients with colorectal cancer.Methods:Specimens from 217 patients with colorectal cancer who underwent surgical resection and were pathologically confirmed in Shanxi Province Cancer Hospital from January 2020 to December 2021 were selected, and the clinical data of the patients were retrospectively analyzed. The mutation status of KRAS, NRAS and BRAF V600E genes were detected in the paraffin specimens of surgically-resected tissues by direct sequencing. The mutation rates of KRAS, NRAS and BRAF V600E were compared among patients with different clinicopathological characteristics.Results:The mutation rates of KRAS, NRAS and BRAF V600E in 217 patients with colorectal cancer were 48.4% (105/217), 4.1% (9/217) and 3.7% (8/217), of which 1 patient (0.5%) had both KRAS and NRAS mutations. NRAS gene mutation was not correlated with gender, age, tumor size, tumor location, pathological type, degree of differentiation, depth of invasion, lymph node metastasis, distant metastasis, TNM stage, hemangioma thrombus/nerve invasion (all P>0.05); KRAS mutation rate in patients ≥ 60 year old was higher than that in patients < 60 year old [55.3% (63/114) vs. 40.8% (42/103), χ2 = 4.55, P = 0.033),and there was no correlation between KRAS gene mutation and other clinicopathological features (all P > 0.05); the mutation rate of BRAF V600E gene in colorectal cancerpatients with distant metastasis was higher than that in patients without distant metastasis [16.7% (4/24) vs. 2.1% (4/193), P = 0.006], and there was no correlation between BRAF V600E gene mutation and other clinicopathological features (all P > 0.05). Conclusions:Older colorectal cancer patients may be prone to KRAS gene mutation, and the BRAF V600E gene mutation rate is higher in patients with distant metastasis, and there is no correlation between NRAS gene mutation and clinicopathological characteristics.

Objective:To analyze the correlation between 21-gene recurrence score (RS) and clinicopathological characteristics of patients with Lumina type breast cancer, and to explore its significance in individualized treatment.Methods:The clinicopathological data of 59 patients with surgical resection and pathological diagnosis of Lumina type breast cancer in Shanxi Provincial Cancer Hospital from May 2018 to May 2019 were retrospectively analyzed. Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression of 21 gene and RS was calculated. According to the 21-gene RS, the patients were divided into low recurrence risk group (RS < 18 points), intermediate recurrence risk group (RS 18-31 points) and high recurrence risk group (RS > 31 points). Univariate and multivariate logistic regression analyses were made to evaluate the correlations between different recurrence risk and clinicopathological characteristics of patients and their influence on the choice of adjuvant chemotherapy.Results:Based on the 21-gene RS, 29 patients were in low recurrence risk group, 22 cases were in intermediate recurrence risk group, and 8 cases were in high recurrence risk group. Single-factor analysis showed that age ( P = 0.012), maximum mass diameter ( P = 0.031), histological grade ( P = 0.036), progesterone receptor (PR) level ( P = 0.015), Ki-67 positive index ( P = 0.049) and molecular typing ( P = 0.010) were influencing factors of 21-gene RS recurrence risk. Multivariate logistic regression analysis showed that the age and Ki-67 positive index were negatively correlated with 21-gene RS recurrence risk (both P < 0.05). After grouping according to the 21-gene RS, 17 patients in the intermediate recurrence risk group (according to the traditional postoperative recurrence risk grouping method for breast cancer) were classified as low recurrence risk group, and 4 patients in the low recurrence risk group were classified as intermediate recurrence risk group ( χ2 = 4.535, P = 0.033). After grouping based on 21-gene RS, the number of patients who needed chemotherapy in individualized treatment decreased. Of the 17 cases, 11 cases did not undergo postoperative chemotherapy, and the remaining patients received chemotherapy. The postoperative follow-up period was 11-22 months. As of March 2020, there was no recurrence or disease progress. Conclusion:The 21-gene RS can provide objective basis for the individualized precise treatment and prognosis prediction for patients with early-stage Lumina type breast cancer.