Background. CD8(+) T lymphocytes are known to play a critical role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, systematic analyses of CD8(+) T cell (Cytotoxic T cells, Tc) subsets in COPD patients have yet to be well conducted. Methods. The whole Tc subsets, including Tc1/2/10/17, CD8(+) regulatory T cells (Tregs) and CD8(+) α7(+) T cells, were quantified by flow cytometry in peripheral blood from 24 stable COPD subjects (SCOPD), 14 patients during acute exacerbations (AECOPD), and 14 healthy nonsmokers (HN). Results. Acute exacerbations of COPD were accompanied by elevated levels of circulating CD8(+) T cells. Tc1 cells were increased in both SCOPD and AECOPD patients, whereas the percentage of Tc2 cells was decreased in SCOPD patients but remained normal in AECOPD patients. Tc17 cells were increased only in AECOPD patients, and the percentage of Tc10 cells was reduced in both SCOPD and AECOPD patients. The imbalances of pro/anti-inflammatory Tc subsets observed in COPD may be caused by the lack of Tc10 cells and the impaired anti-inflammatory capacity of CD8(+) Tregs. Conclusions. The imbalances between subsets of CD8(+) peripheral blood T cells contribute to the immune response dysfunction in COPD pathogenesis.
The mu-opioid receptor (MOR), a membrane-bound G protein-coupled receptor, is the main target for opioids in the nervous system. MOR1 has been found in several types of cancer cells and reported to be involved in tumor progression and metastasis. However, the expression and clinical significance of MOR1 in esophageal squamous cell carcinoma (ESCC) remain unclear. In our study, the expression of MOR1 was confirmed in ESCC cell lines (KYSE180, KYSE150, and EC109) by Western blot. MOR1 was also detected on tissue microarrays of ESCC samples in 239 cases using immunohistochemical staining. We found that MOR1 was mainly located in the cytoplasm and occasionally occurred in the membrane or nucleus of ESCC cells. Moreover, results indicated that MOR1 expression in the cytoplasm was associated with lymph node metastasis (R = 0.164, P = 0.008, Kendall's tau-b-test). No more associations were found between MOR1 expression status and other clinical parameters. However, no statistical significant differences were found between MOR1 expression in the cytoplasm, nucleus/membrane, and the overall survival of ESCC patients (P = 0.848; P = 0.167; P = 0.428, respectively, log-rank test). Our results suggest that the cytoplasmic MOR1 may be a high-risk factor for lymph node metastasis of ESCC patients. We also hypothesize that MOR1 agonists used in ESCC patients should be prudent, and opioid receptor antagonists may be novel therapeutic drugs for ESCC patients.
Background: Cytokines modulate the glioma tumor microenvironment, influencing occurrence, progression, and treatment response. Strategic cytokine application may improve glioma immunotherapy outcomes. Gliomas remain refractory to standard therapeutic modalities, but immunotherapy shows promise given the integral immunomodulatory roles of cytokines. However, systematic evaluation of cytokine glioma immunotherapy research is absent. Bibliometric mapping of the research landscape, recognition of impactful contributions, and elucidation of evolutive trajectories and hot topics has yet to occur, potentially guiding future efforts. Here, we analyzed the structure, evolution, trends, and hotspots of the cytokine glioma immunotherapy research field, subsequently focusing on avenues for future investigation. Methods: This investigation conducted comprehensive bibliometric analyses on a corpus of 1529 English-language publications, from 1 January 2000, to 4 October 2023, extracted from the Web of Science database. The study employed tools including Microsoft Excel, Origin, VOSviewer, CiteSpace, and the Bibliometrix R package, to systematically assess trends in publication, contributions from various countries, institutions, authors, and journals, as well as to examine literature co-citation and keyword distributions within the domain of cytokines for glioma immunotherapy. The application of these methodologies facilitated a detailed exploration of the hotspots, the underlying knowledge structure, and the developments in the field of cytokines for glioma immunotherapy. Results: This bibliometric analysis revealed an exponential growth in annual publications, with the United States, China, and Germany as top contributors. Reviews constituted 17% and research articles 83% of total publications. Analysis of keywords like “interleukin-13,” “TGF-beta,” and “dendritic cells” indicated progression from foundational cytokine therapies to sophisticated understanding of the tumor microenvironment and immune dynamics. Key research avenues encompassed the tumor microenvironment, epidermal growth factor receptor, clinical trials, and interleukin pathways. This comprehensive quantitative mapping of the glioma immunotherapy cytokine literature provides valuable insights to advance future research and therapeutic development. Conclusion: This study has identified remaining knowledge gaps regarding the role of cytokines in glioma immunotherapy. Future research will likely focus on the tumor microenvironment, cancer vaccines, epidermal growth factor receptor, and interleukin-13 receptor alpha 2. Glioma immunotherapy development will continue through investigations into resistance mechanisms, microglia and macrophage biology, and interactions within the complex tumor microenvironment.
Abstract Background T cell receptor (TCR)-T cells possess similar effector function, but milder and more durable signal activation compared with chimeric antigen receptor-T cells. TCR-T cell therapy is another active field of cellular immunotherapy for cancer. Methods We previously developed a human anti-CD19 antibody (ET190L1) and generated novel CD19-specific γ/δ TCR-T cells, ET019003, by fusing the Fab fragment of ET190L1 with γ/δ TCR constant chain plus adding an ET190L1-scFv/CD28 co-stimulatory molecule. ET019003 cells were tested in preclinical studies followed by a phase 1 clinical trial. Results ET019003 cells produced less cytokines but retained comparable antitumor potency than ET190L1-CAR-T cells in vivo and in vitro. In the first-in-human trial, eight patients with relapsed or refractory DLBCL were treated. CRS of grade 1 was observed in three (37.5%) patients; ICANS of grade 3 was noted in one (12.5%) patient. Elevation of serum cytokines after ET019003 infusion was almost modest. With a median follow-up of 34 (range 6–38) months, seven (87.5%) patients attained clinical responses and six (75%) achieved complete responses (CR). OS, PFS and DOR at 3 years were 75.0%, 62.5%, and 71.4%, respectively. Notably, patient 1 with primary CNS lymphoma did not experience CRS or ICANS and got an ongoing CR for over 3 years after infusion, with detectable ET019003 cells in CSF. ET019003 showed striking in vivo expansion and persisted in 50% of patients at 12 months. Three patients received a second infusion, one for consolidation therapy after CR and two for salvage therapy after disease progression, but no response was observed. ET019003 expansion was striking in the first infusion, but poor in the second infusion. Conclusions CD19-specific γ/δ TCR-T cells, ET019003, had a good safety profile and could induce rapid responses and durable CR in patients with relapsed or refractory DLBCL, even primary CNS lymphoma, presenting a novel and potent therapeutic option for these patients. Trial registration : NCT04014894.
The incidence of papillary thyroid microcarcinoma (PTMC) has been increasing globally in the past few decades. PTMC does not have a distinctive morphology that results in differences in biological behavior. The aim of this study was to classify PTMCs according to the morphological features and explore the relationship with clinicopathological characteristics. Additionally, we sought to evaluate whether different variants of PTMC can be an independent predictor for lymph mode metastasis when considering other risk factors. Between December 2014 and December 2015, 1041 PTMC cases undergoing surgical resection at Tianjin Medical University Cancer Institute and Hospital were reviewed retrospectively. Statistical analysis was performed to investigate the independent factors for lymph node metastasis in PTMC. Conventional variant PTMC (CPTMC), follicular variant PTMC (FPTMC), and encapsulated variant PTMC (EnPTMC) were major variants in PTMC, collectively accounting for 96.7% of the entire PTMC cohort.There were significant differences in clinicopathological characteristics among the three major variants. The frequency of aggressive parameters was significantly different among the three variants, including tumor size, minimal extrathyroidal extension (minimal ETE), and lymph node metastasis (all P < 0.05), being highest in CPTMC, lowest in EnPTMC, and intermediate in FPTMC. FPTMC (OR = 0.642, P = 0.003) and EnPTMC (OR = 0.540, P = 0.041) were independent protective factors for lymph node metastasis (LNM). In contrast, male gender (OR = 1.836, P = 0.000), age less than 45 years (OR = 1.457, P = 0.009), tumor size greater than 0.5 cm (OR = 1.453, P = 0.007), calcification (OR = 1.465, P = 0.016), minimal ETE (OR = 1.801, P = 0.001), and multifocality (OR = 1.721, P = 0.000) were independent risk factors for LNM. The present study demonstrates the distinct biological behaviors of the three major PTMC variants and establishes an aggressive order of CPTMC ≫ FPTMC > EnPTMC. It is necessary to take into consideration variant-related risks and other independent predictors for the determination of lymphadenectomy in patients with PTMC.
The expression of programmed cell death ligand 1 (PD-L1) as a biomarker for immunotherapy in non-small cell lung cancer (NSCLC) is routinely detected in clinical pathology department. However, the spatial heterogeneity of PD-L1 expression in intrapulmonary tumors and extrapulmonary metastases is still a challenge for the clinical testing. This study aims to explore the differences of PD-L1 expression in test samples obtaining from different sites of NSCLC. This study may contribute to the detection strategy of PD-L1 in patients with advanced lung cancer.One hundred and thirty-one cases of consecutively detected PD-L1 (22c3 assay, Dako) staining in metastatic NSCLC and 972 cases of non-paired intrapulmonary NSCLC were collected. The discrepancies of tumor proportion score (TPS) of PD-L1 expression in intrapulmonary samples and extrapulmonary metastatic samples of different sites were compared.The positive expression rate of PD-L1 in extrapulmonary metastatic NSCLC (TPS ≥ 1%) was 61.83%, and the TPS was significantly higher than that in intrapulmonary tumors (P=0.03). The PD-L1 scores of the specimens obtained from different sites were significantly different (P=0.007). The positive rates of PD-L1 in liver and adrenal metastases were 85.71% and 77.78% respectively, and their TPS were significantly higher than that of the intrapulmonary samples (P<0.05). The positive rates of PD-L1 in lymph node, bone, brain, soft tissue, and pleural metastases was 40.00%-66.67%, with no significant differences compared to intrapulmonary tumors. The analysis of histological subtype and sample type showed that the PD-L1 score of extrapulmonary samples of adenocarcinoma subtype or surgical specimen was significantly higher than that of intrapulmonary tumors. The analysis of clinicopathological parameters showed that the PD-L1 positive expression or high expression were significantly correlated with male patients, smoking history, and epidermal growth factor receptor (EGFR) wild type.The expression of PD-L1 in metastatic NSCLC is generally higher than that in intrapulmonary tumor, and the positive rate of PD-L1 expression was discrepant in different sites of specimen. The differences of PD-L1 score between extrapulmonary metastatic samples and intrapulmonary samples may be associated with different metastatic sites, histological subtype, and specimen type.【中文题目：非小细胞肺癌不同部位组织样本PD-L1 表达水平比较研究】 【中文摘要：背景与目的 程序性死亡配体1（programmed cell death ligand 1, PD-L1）作为非小细胞肺癌（non-small cell lung cancer, NSCLC）免疫治疗患者分层标志物已进入临床病理常规检测。然而PD-L1表达在肺内和肺外不同转移部位的空间异质性是困扰临床检测的难题。本研究旨在探讨NSCLC不同部位组织样本的PD-L1表达评分的差异，从而有助于晚期肺癌患者的PD-L1检测策略的制定。方法 回顾性收集PD-L1（22c3抗体，Dako）临床病理连续检测的131例肺外转移性NSCLC以及同期非配对肺内肿瘤972例进行对照分析，对比肺外与肺内肿瘤组织样本检测的PD-L1肿瘤阳性比例评分（tumor proportion score, TPS）差异。结果 肺外转移性NSCLC的PD-L1阳性表达率（TPS≥1%）为61.83%，TPS评分显著高于同期肺内肿瘤（P=0.03）。不同部位组织样本的PD-L1表达评分具有显著差异（P=0.007）。肝脏和肾上腺转移瘤的PD-L1阳性率高，分别为85.71%和77.78%，其TPS评分均显著高于肺内肿瘤（P<0.05）。淋巴结、骨、脑、软组织和胸膜转移瘤的PD-L1表达率为40.00%-66.67%，TPS评分与肺内肿瘤无显著差异。组织学和样本类型分析显示，腺癌类型和手术切除的肺外样本PD-L1表达评分显著高于同类型肺内肿瘤。临床病理参数分析显示，PD-L1阳性表达和高表达均与患者男性、吸烟史以及表皮生长因子受体（epidermal growth factor receptor, EGFR）野生型显著相关。结论 肺外转移性NSCLC样本的PD-L1表达评分高于肺内肿瘤，且不同部位组织样本的PD-L1表达阳性率存在差异。肺外转移性肿瘤与肺内肿瘤的PD-L1检测差异可能与不同转移部位、组织学和样本类型相关。 】 【中文关键词：肺肿瘤；程序性死亡配体1；异质性；肿瘤阳性比例评分】.
Endometrial clear cell carcinoma (ECCC) and clear cell adenocarcinoma of the cervix (CCAC) are uncommon gynecologic cancers that have morphologic and phenotypic features similar to ovarian clear cell carcinoma (OCCC), but the 3 entities may not be completely identical. This study identified the morphologic and phenotypic characteristics and the differences between ECCC and CCAC in comparison to OCCC. The morphologic features of 16 ECCCs, 7 CCACs, and 22 OCCCs are described. The immunoprofiles of hepatocyte nuclear factor (HNF) 1β, napsin A, estrogen, progesterone, p53, and Ki-67 were assessed. The results confirm that clear cell carcinomas of the gynecologic tract have a similar spectrum of histopathologic features with the exception that ECCCs have focal solid components more often than CCACs and OCCCs and ECCCs have a slightly higher average mitotic index. Similar to OCCCs, both ECCCs and CCACs were positive for HNF1β and napsin A, and rarely expressed estrogen and progesterone. HNF1β was a sensitive marker for clear cell carcinoma at all 3 sites. Napsin A was less sensitive in ECCCs than in OCCCs (56.3% vs. 90.9%, P =0.021). The average Ki-67 index was higher in ECCCs than in OCCCs (52.6% vs. 39.1%) in hotspot scoring, and more ECCC cases had a higher expression (56.3% vs. 22.7%). Diffuse p53 expression, which is associated with TP53 mutation, was observed slightly more often in ECCCs than in OCCCs (25% vs. 9.1%). Our findings revealed morphologic and immunophenotypic similarities and differences among different gynecologic clear cell carcinomas, which may help in improving diagnosis and knowledge of CCC in the female genital tract.
The role of inducible costimulator (ICOS) signaling in chronic obstructive pulmonary disease (COPD) has not been fully elucidated.We compared the percentages of ICOS+ T cells and ICOS+ regulatory T (Treg) cells in CD4+ T cells and CD4+CD25+FOXP3+ Tregs, respectively, in the peripheral blood of smokers with or without COPD to those in healthy controls. We further characterized their phenotypes using flow cytometry. To investigate the influence of ICOS signaling on C-X-C motif chemokine receptor 3 (CXCR3) expression in COPD, we evaluated the expression levels of ICOS and CXCR3 in vivo and in vitro.ICOS expression was elevated on peripheral CD4+ T cells and CD4+ Tregs of COPD patients, which positively correlated with the severity of lung function impairment in patients with stable COPD (SCOPD), but not in patients with acute exacerbation of COPD (AECOPD). ICOS+CD4+ Tregs in patients with SCOPD expressed higher levels of coinhibitors, programmed cell death protein 1 (PD-1) and T-cell immunoreceptor with Ig and ITIM domains (TIGIT), than ICOS-CD4+ Tregs, whereas ICOS+CD4+ T cells mostly exhibited a central memory (CD45RA-CCR7+) or effector memory (CD45RA-CCR7-) phenotype, ensuring their superior potential to respond potently and quickly to pathogen invasion. Furthermore, increased percentages of CXCR3+CD4+ T cells and CXCR3+CD4+ Tregs were observed in the peripheral blood of patients with SCOPD, and the expression level of CXCR3 was higher in ICOS+CD4+ T cells than in ICOS-CD4+ T cells. The percentage of CXCR3+CD4+ T cells was even higher in the bronchoalveolar lavage fluid than in matched peripheral blood in SCOPD group. Lastly, in vitro experiments showed that ICOS induced CXCR3 expression on CD4+ T cells.ICOS signaling is upregulated in COPD, which induces CXCR3 expression. This may contribute to increased numbers of CXCR3+ Th1 cells in the lungs of patients with COPD, causing inflammation and tissue damage.
Sal-like 4(SALL4) is significant for maintaining self-renewal and pluripotency in embryonic stem cells, cancer cells and perhaps even cancer stem cells. The expression of SALL4 has been recorded in various kinds of cancers and is deemed to have a clinical value for diagnosis. However, little information on SALL4 expression has been illustrated in breast cancer. In this study, the expression of SALL4 was scrutinized by immunohistochemical analysis in breast invasive ductal carcinoma in a large cohort of 160 patients. High cytoplasmic expression of SALL4 was detected in breast cancer tissues compared with normal adjacent tissues. High SALL4 expression was associated with advanced tumor invasion (p = 0.019), lymph node stage (p = 0.027), ER (p = 0.030), PR (p = 0.037), HER2 (p = 0.019) and TNBC (p = 0.007) in overall patients. Interestingly, in Kaplan-Meier analysis, breast cancer patients with high expression of SALL4 demonstrated a worse OS. Both univariate and multivariate analysis illustrated that examination of SALL4 was of great prognostic value in OS. Thus, our data showed that high cytoplasmic expression of SALL4 was considered to be an independent prognostic indicator for breast invasive ductal carcinoma.
Objective: To explore the origin of ovarian high grade serous carcinoma (HGSC) through analysing the expression and significance of PAX8, PAX2, p53 and RAS in the ovary and fallopian tube of different types and grades of serous carcinoma. Methods: A total of 44 cases tissue samples of ovarian tumor including 34 malignant ovarian tumor and 10 normal normal tissue (as control group) were collected from the admitted patients in Affiliated Tumor Hospital of Guangxi Medical University from January 2015 to January 2016. Fallopian tube tissues were segmented in accordance with the fimbria, ampulla, isthmus and the corresponding ovarian tissues were by the side. There were 34 cases of patients with ovarian cancer including 29 cases of epithelial ovarian cancer (27 serous carcinoma, 1 mucinous carcinoma,1 endometrioid adenocarcinoma) and 5 non-epithelial ovarian cancer (sex cord-interstitial tumor). Among 27 cases of patients with ovarian serous cancer, there were 23 HGSC and 4 low-grade ovarian serous cancer (LGSC). One hundred fifty-three cases of samples were diagnosed as ovarian serous cancer by Shandong University Affiliated Qilu Hospital from 2005 to 2013 and these samples were made tissue microarray. (1) To analyze the expression and differences of PAX8, PAX2, p53 and RAS in the above tissues and tissue microarray from ovarian and tubal of HGSC and control women by immunohistochemistry methods. (2) To compare the expression levels of PAX8, PAX2, p53 and RAS in ovarian and fallopian tubes of ovarian cancer patients with different pathological types. (3) To analyze the correlations of tubal and ovarian tissue in PAX8, PAX2, p53 and RAS expression of HGSC. (4) To analyze the factors of the prognosis of ovarian serous cancer in tissue microarray by single factor analysis method. Results: (1) PAX8, PAX2, p53 and RAS expression was negative in normal ovarian epithelium of control group, but the expression of PAX8, PAX2, p53 and RAS were strongly positive brown in secrete cells of normal fallopian tube epithelium. (2) p53 and RAS expression of fallopian tube epithelium in the epithelial ovarian cancer group were significantly higher than those in the non-epithelial ovarian cancer groups (P<0.05), but the expression of PAX8 and PAX2 in fallopian tube and the expression of PAX8, PAX2, p53 and RAS in ovarian tissue was not statistically significant in the groups (P>0.05). PAX8, PAX2 and p53 expression of the ovarian in HGSC group were significantly higher than those in LGSC group (P<0.05), while the expression of RAS was lower in the ovarian of the high-grade group (P<0.05), while the expression of PAX8, PAX2, p53 and RAS in fallopian tube was not statistically significant in the groups (P>0.05). (3) There was a significantly positive correlation between fallopian tube and the corresponding ovary of HGSC in PAX8 and PAX2 expression (r=0.422, P=0.045; r=0.693, P=0.000), but not correlation in p53 and RAS expression (r=0.058, P=0.793; r= -0.190, P=0.384). (4) Univariate survival analysis showed that the progression free survival time in patients with ovarian serous cancer group was significantly correlated with the protein expression of PAX8, PAX2 and RAS (P<0.05), but there were not correlated with age, surgical staging, cell differentiation, lymph node metastasis and preoperative chemotherapy and p53 protein expression (P>0.05). The total survival time in patients with ovarian serous cancer group was significantly correlated with the protein expression of PAX8 (P<0.05), but there were not correlated with age,surgical staging, cell differentiation, lymph node metastasis and preoperative chemotherapy and the protein expression of PAX2, RAS and p53 (P>0.05). Conclusions: PAX8, PAX2, p53, RAS are of great significance for the study of origin of HGSC. HGSC may be derived from fallopian tube, but further investigation would be necessary to confirm this. PAX8, PAX2, p53, RAS could be expected to be used as predictors of survival prognosis in patients with ovarian serous cancer.目的： 探讨配对盒基因8抗体（PAX8）、配对盒基因2抗体（PAX2）、p53和ras癌基因（RAS）蛋白在高级别卵巢浆液性癌（HGSC）患者的卵巢及输卵管组织中的表达，并分析其对于HGSC起源的意义。 方法： （1）组织标本：收集2015年1月—2016年1月广西医科大学附属肿瘤医院收治的34例卵巢恶性肿瘤患者的组织标本，以同期因卵巢良性疾病等行手术治疗患者的卵巢和输卵管无病变区域的组织标本10份作为对照。其中，卵巢组织标本的取材按左、右侧区分，输卵管组织标本的取材按左、右侧区分并按伞部、壶腹部、峡部解剖分段取材。34例卵巢恶性肿瘤患者中，上皮性恶性肿瘤29例（包括浆液性癌27例、黏液性癌1例、子宫内膜样腺癌1例）、非上皮性恶性肿瘤5例（均为性索-间质肿瘤）；27例卵巢浆液性癌患者中，HGSC 23例、低级别卵巢浆液性癌（LGSC）4例。（2）组织芯片：采用由山东大学齐鲁医院制作并赠送的组织芯片，该芯片收集了2005—2013年手术切除并经病理诊断明确为卵巢浆液性癌的组织标本153份。采用免疫组化SP法检测上述组织标本和组织芯片中PAX8、PAX2、p53和RAS蛋白的表达，（1）分析HGSC患者和对照妇女的卵巢和输卵管组织中PAX8、PAX2、p53及RAS蛋白的定位表达差异；（2）比较不同病理类型卵巢恶性肿瘤患者的卵巢和输卵管组织中PAX8、PAX2、p53及RAS蛋白表达水平的差异；（3）分析PAX8、PAX2、p53、RAS蛋白在HGSC患者输卵管组织中的表达水平与其对应卵巢组织中表达水平的相关性；（4）采用单因素生存分析法对组织芯片中卵巢浆液性癌患者的预后影响因素进行分析。 结果： （1）对照妇女的正常卵巢上皮细胞中PAX8、PAX2、p53、RAS蛋白均呈阴性表达，而正常输卵管上皮分泌型细胞中PAX8、PAX2、p53、RAS蛋白均呈棕褐色强阳性表达。HGSC患者的输卵管上皮分泌型细胞中及卵巢和输卵管的癌细胞中PAX8、PAX2、p53、RAS蛋白均呈棕褐色强阳性表达。（2）上皮性卵巢恶性肿瘤患者的输卵管组织中p53、RAS蛋白的表达水平均明显高于非上皮性卵巢恶性肿瘤患者（P<0.05）；但两者的输卵管组织中PAX8、PAX2蛋白以及卵巢组织中PAX8、PAX2、p53、RAS蛋白的表达水平比较均无明显差异（P>0.05）。HGSC患者的卵巢组织中PAX8、PAX2和p53蛋白的表达水平均明显高于LGSC患者（P<0.05），RAS蛋白的表达水平明显低于LGSC患者（P<0.05）；而两者的输卵管组织中PAX8、PAX2、p53、RAS蛋白的表达水平分别比较均无明显差异（P>0.05）。（3）PAX8、PAX2蛋白在HGSC患者输卵管组织中的表达水平与其对应卵巢组织中的表达水平均呈明显正相关（r=0.422，P=0.045；r=0.693，P=0.000）；但p53和RAS蛋白在输卵管组织中的表达水平与其对应卵巢组织中的表达水平均无相关性（r=0.058，P=0.793；r=-0.190，P=0.384）。（4）单因素生存分析显示，卵巢浆液性癌患者的无进展生存时间与PAX8、PAX2、RAS蛋白表达均明显相关（P<0.05）；而与年龄、手术病理分期、病理分化程度、淋巴结转移状态、术前化疗以及p53蛋白表达均无关（P>0.05）。卵巢浆液性癌患者的总生存时间与PAX8蛋白表达有关，而与年龄、手术病理分期、病理分化程度、淋巴结转移状态、术前化疗以及PAX2、p53、RAS蛋白表达均无关（P>0.05）。 结论： PAX8、PAX2、p53、RAS蛋白对于研究HGSC的起源定位于输卵管上皮分泌型细胞有着重要的意义，HGSC可能来源于输卵管，但需更深入的研究来证实；PAX8、PAX2、p53、RAS蛋白有望作为卵巢浆液性癌患者预后的预测指标。.
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