Clinical significance of peripheral blood and tumor tissue lymphocyte subsets in cervical cancer patients.

BACKGROUND: Alterations in peripheral blood lymphocytes in cervical cancer have been reported, although conflicting views exist. The present study investigated the distributions of lymphocyte subsets in tumor tissue and peripheral blood samples from cervical cancer patients and precancerous lesion patients, and evaluated the correlations of lymphocyte subsets with clinicopathological and prognostic variables. METHODS: A total of 44 patients with stage IB1-IIA2 cervical cancer and 13 precancerous lesion patients were included. Lymphocytes were collected from the tumor tissue and the peripheral blood, and isolated by Lymphoprep density gradient centrifugation. The percentages of lymphocyte subsets were quantified by flow cytometry analysis, and the differences between lymphocyte subsets in the tumor tissue and peripheral blood were compared by SPSS. In addition, the relationships between lymphocyte subsets and clinicopathological and prognostic variables were analyzed. RESULTS: Our results revealed that the amount of total T lymphocytes, CD8+ T cells, granulocytes, pDCs, CD16+ monocytes and CD56high NK cells were significantly higher in the tumor tissue than in the peripheral blood in the cervical cancer patients, while those of CD4+ T cells, CD4+/CD8+ cell ratio, rdT cells, BDCA1+ mDCs, total monocytes, CD14+ monocytes, NK cells and CD56low NK cells exhibited the opposite trend (p < 0.05). The levels of total pDCs and BDCA1+ mDCs in the peripheral blood were significantly lower in the cervical cancer patients than in the precancerous lesion patients, while the proportion of CD16+ monocytes was elevated (p < 0.05). In addition, some lymphocyte subsets, especially CD4+ cells and CD8+ cells, and the CD4+/CD8+ cell ratio were closely associated with clinicopathological and prognostic parameters. CONCLUSIONS: These results suggested that distinct alterations in infiltrating lymphocyte subsets occurred in the tumor and were associated with clinicopathological and prognostic parameters. Systemic impairment of the immune system may occur in the antitumor response of cervical cancer patients.

Individualized proximal margin correlates with outcomes in gastric cancers with radical gastrectomy.

The length of proximal margin for gastrectomy remains controversial. The proximal margin and its relationships with clinicopathological variables and overall survival of 922 gastric cancers were retrospectively analyzed. Proximal margin was divided into four groups (0-2.0, 2.1-4.0, 4.1-6.0, and >6.0 cm). It indicated that the overall survival was improved with the increase of proximal margin. The proximal margin of 2.1-4.0 cm was associated with a better overall survival for gastric cancers with solitary-type (T1 and T2 stages, N0 stage, tumor-node-metastasis stages I and II, tumor size <5 cm, histological G1 and G2, and Bormann type I and II). Futhermore, proximal margin of 4.1-6.0 cm was associated with a better overall survival for gastric cancers with infiltrative-type (T3 and T4 stages, N1 stage, tumor-node-metastasis stage III, tumor size ⩾5 cm, histological G3 and G4, and Bormann type III and IV). Univariate analysis revealed that T stage, N stage, tumor-node-metastasis stage, histological grade, Bormann type, carcinoembryonic antigen, carbohydrate antigen 199, extent of gastrectomy, tumor location, and proximal margin were significantly associated with overall survival. Multivariate analysis revealed that tumor-node-metastasis stage, histological grade, Bormann type, carcinoembryonic antigen, carbohydrate antigen 199, extent of gastrectomy, and proximal margin were independent prognostic factors for gastric cancers with radical gastrectomy. In conclusion, the proximal margin was an independent prognostic factor for gastric cancer and should be decided individually. Proximal margin of 2.1-4.0 cm and 4.1-6.0 cm were needed for patients with solitary-type and infiltrative-type, respectively.

Clinicopathological and prognostic significance of survivin expression in renal cancer patients: a meta-analysis.

BACKGROUND: Survivin has been reported to play a role in the diagnosis and prognosis of renal cell carcinoma (RCC); however, published data on this subject are conflicting. AIM: To conduct a meta-analysis to evaluate the impact of survivin as a prognostic marker and its association with clinicopathological variables in patients with RCC. METHOD: Comprehensive searches of electronic databases (PubMed, ISI Web of Knowledge Embase, Google Scholar Web and the Cochrane Library) were updated to June 2016 to retrieve eligible studies. The association strength was measured with relative risks (RRs) and pooled HRs with 95% CIs, which were extracted and pooled to determine the association between survivin expression and patient survival and clinicopathological features. RESULTS: Ten studies with 1063 cases of RCC were included. Positive survivin expression in RCC was associated with the TNM stage (pooled RR 1.49; 95% CI 1.07 to 2.07) or Fuhrman grade (pooled RR 1.63; 95% CI 1.15 to 2.32) in patients. The correlation between survivin expression and gender was not significant (pooled RR 0.97; 95% CI 0.83 to 1.15). In addition, a considerable association was found between survivin expression and overall survival for patients with RCC (pooled HR 1.94; 95% CI 1.24 to 3.05 (multivariate model) and 5.41; 95% CI 4.08 to 7.17 (univariate model)). CONCLUSIONS: Our results indicate that survivin is of prognostic significance in patients with RCC.

Loss of FBXW7 expression is associated with poor prognosis in intrahepatic cholangiocarcinoma.

AIM: FBXW7 acts as a tumor suppressor gene by targeting several oncogenic regulators of proliferation, growth and apoptosis for proteasomal degradation. However, the significance of this protein is not yet well understood in intrahepatic cholangiocarcinoma (IHCC). In this study, we aimed to investigate the correlation between FBXW7 expression and clinicopathological variables in IHCC patients. METHODS: Thirty-one patients with IHCC who underwent hepatic resection were enrolled. FBXW7 expression in tumor tissue was determined by immunohistochemistry and patients were divided into two groups, the FBXW7 high expression group (n = 11) and the FBXW7 low expression group (n = 20). We then compared clinicopathological variables including prognosis between the high and low expression groups in tumor tissue. RESULTS: FBXW7 expression was significantly correlated with staging (P = 0.006), and tended to correlate with lymph node metastasis. The FBXW7 low expression group had significantly poorer prognosis compared with the FBXW7 high expression group (P = 0.020); 3-year survival rates were 29.4% and 72.7%, respectively. Furthermore, the disease-free survival rate in the FBXW7 low expression group was significantly worse than in the FBXW7 high expression group (P = 0.022). On multivariate analysis, intrahepatic metastasis (P = 0.006) was a significant independent prognostic factor for disease-free survival, and FBXW7 low expression tended to be an independent prognostic factor for both overall (P = 0.067) and disease-free survival (P = 0.083). CONCLUSION: Our results confirmed that low expression of FBXW7 in IHCC correlates with tumor progression and poor prognosis in IHCC.

Colorectal Cancer in Correlation With Clinicopathological Variables: The Effects of Hypoxia-Inducible Factor-1 Alfa or the InterLeukin-33 and Vascular Endothelial Growth Factor?

Background The hypoxia-inducible factor-1 alpha (HIF-1α) is believed to control angiogenesis and metabolism by upregulating hypoxia-induced genes, such as the interLeukin-33 (IL-33) gene and vascular endothelial growth factor (VEGF) gene. The study aimed to study the HIF-1α and its two hypoxia pathway genes; IL-33 and VEGF, together with the angiogenesis and correlate them with some prognostic clinicopathological features, separately and in combination to assess their dependency. Methodology This study included 87 colorectal cancer (CRC) cases, diagnosed between January 2019 and December 2022. Different prognostic clinicopathological features were examined and tissue microarray (TMA) slides were designed to carry out IHC for IL-33 and VEGF scoring in tumor cells, in addition to qualitative interpretation of VEGF expression in tumor vessels. Molecular analysis was performed for HIF-1α and all data were correlated to the clinicopathological features, separately and collectively, to assess the dependency of these factors. Results No statistical correlation could be seen among the IL-33, VEGF, and prognostic clinicopathological features. Whereas analysis of the HIF-1α alone showed significantly high mean expression in patients with distance metastasis and was increased with the increased involvement of the lymph nodes (LNs). However, when the HIF 1-α expression was correlated with the clinicopathological characteristics on the bases of VEGF and IL-33 expressions the significant association with metastasis disappeared in tumor cells and appeared only with the endothelium of the tumor angiogenesis. Moreover, the results conflicted with the LNs involvement. Conclusions These findings may suggest a role of HIF 1-α in the downstream regulation of biomarkers other than the VEGF and IL-33, which needs to uncover pathways and novel factors regulated by the HIF 1-α for the proinflammation and angiogenesis in malignancy.

MAPK9 is Correlated with a Poor Prognosis and Tumor Progression in Glioma.

BACKGROUND: Glioma has a high incidence in young and middle-aged adults and a poor prognosis. Because of late diagnosis and uncontrollable recurrence of the primary tumor after failure of existing treatments, glioma patients tend to have a poor prognosis. Recent advances in research have revealed that gliomas exhibit unique genetic features. Mitogen-activated protein kinase 9 (MAPK9) is significantly upregulated in mesenchymal glioma spheres and may be a new target for glioma diagnosis. This study aimed to investigate the potential diagnostic significance and predictive value of MAPK9 in glioma. METHODS: Paraffin-embedded tumor tissues and paracancerous tissues were collected from 150 glioma patients seen at the General Hospital of Northern Theater Command. Immunohistochemistry and western blot assays were used to detect the expression levels of MAPK9. Prognosis and survival analyses were performed using SPSS 26 software for univariate/multivariate analysis and log-rank analysis. Cellular models were used to assess the effect of MAPK9 overexpression and knockdown in vitro. RESULTS: MAPK9 expression was higher in glioma tissues than in paraneoplastic tissues. Prognostic and survival analyses revealed that the MAPK9 expression level is an independent prognostic factor in glioma patients. In addition, overexpression of MAPK9 significantly promoted the proliferation and migration of primary glioma cells, possibly via the Wnt/ß-catenin-regulated EMT pathway. CONCLUSIONS: MAPK9 is an independent prognostic factor in glioma and is involved in tumor progression.

Overexpression of PRKCH promotes tumorigenesis in patients with glioma and influences glioma stem cell properties.

BACKGROUND: PRKCH is a member of the PKC family with the potential to regulate cell proliferation and differentiation. Glioma is the most common primary tumor of the central nervous system, with a high recurrence rate and poor prognosis. Recent studies have demonstrated that PRKCH can promote the proliferation of glioma cells. The purpose of this study was to investigate the promoting effect and possible mechanism of PRKCH on glioma development. METHODS: Tumor tissue and paracancerous tissue were collected from 160 glioma patients treated at the General Hospital of Northern Theater Command. The expression level of PRKCH was detected by immunohistochemistry and immunoblotting. Univariate/multivariate analysis and log-rank analysis, as well as prognosis and survival analysis, were performed using SPSS26 software. The PRKCH overexpression model was constructed in vitro to study the effect of PRKCH expression on the characteristics of glioma stem cells. RESULTS: The expression of PRKCH in glioma tissues was higher than that in adjacent tissues. PRKCH expression level is an independent prognostic factor in glioma patients, promoting poor prognosis and shorter survival in glioma patients. Furthermore, overexpression of PRKCH in glioma stem cells significantly increased stem cell properties and enhanced cell viability. Downregulation of PRKCH significantly inhibited the progression of glioma stem cells. CONCLUSION: PRKCH promotes the development of gliomas and may be a therapeutic target for gliomas.

Altered expression of 17­ß­hydroxysteroid dehydrogenase type 2 and its prognostic significance in non­small cell lung cancer.

Numerous studies have reported that oestrogens may contribute to the development of non­small cell lung cancer (NSCLC). Although different steroidogenic enzymes have been detected in the lung, the precise mechanism leading to an exaggerated accumulation of active oestrogens in NSCLC remains unexplained. 17­ß­Hydroxysteroid dehydrogenase type 2 (HSD17B2) is an enzyme involved in oestrogen and androgen inactivation by converting 17­ß­oestradiol into oestrone, and testosterone into 4­androstenedione. Therefore, the enzyme serves an important role in regulation of the intracellular availability of active sex steroids. This study aimed to determine the expression levels of HSD17B2 in lung cancer (LC) and adjacent histopathologically unchanged tissues obtained from 161 patients with NSCLC, and to analyse the association of HSD17B2 with clinicopathological features. For that purpose, reverse transcription­quantitative PCR, western blotting and immunohistochemistry were conducted. The results revealed that the mRNA and protein expression levels of HSD17B2 were significantly decreased in LC tissues compared with matched controls (P<10­6). Conversely, strong cytoplasmic staining of HSD17B2 was detected in the unchanged respiratory epithelium and in glandular cells. Notably, a strong association was detected between reduced HSD17B2 expression and advanced tumour stage, grade and size. Furthermore, it was revealed that HSD17B2 may have potential prognostic significance in NSCLC. A log­rank test revealed the benefit of high HSD17B2 protein expression for the overall survival (OS) of patients (P=0.0017), and multivariate analysis confirmed this finding (hazard ratio=0.21; 95% confidence interval=0.07­0.63; P=0.0043). Stratified analysis in the Kaplan­Meier Plotter database indicated that patients with higher HSD17B2 expression presented better OS and post­progression survival. This beneficial effect was particularly evident in patients with adenocarcinoma and during the early stages of NSCLC. Decreased expression of HSD17B2 appears to be a frequent feature in NSCLC. Retrospective analysis suggests that the HSD17B2 mRNA and protein status might be independent prognostic factors in NSCLC and should be further investigated.

TRIP13 upregulation is correlated with poor prognosis and tumor progression in esophageal squamous cell carcinoma.

Thyroid receptor-interacting protein 13 (TRIP13), a member of the AAA + ATPase super-family, has been proved to be upregulated and identified as a prognostic factor in multiple human cancers, However, the role of TRIP13 in esophageal squamous cell carcinoma (ESCC) and its clinic relevance remains unclear. In the present study, we performed database-mining and detected TRIP13 expression in 158 tissue samples (79 ESCC tissue and 79 matched adjunct non-cancerous tissues). We further investigated the correlation between TRIP13 expression and clinicopathological features and overall survival. Univariate and multivariate Cox regression analyses were applied to evaluate the potential prognostic value of TRIP13 in ESCC patients. In addition, the mechanisms involved in TRIP13 tumor-promoting effect was investigated. Data showed that TRIP13 expression was significantly increased in ESCC tissues, compared with the matched adjunct non-cancerous tissues. Expression of TRIP13 is significantly correlated with T status (P = 0.027), lymphatic metastasis (P = 0.017), and clinical stages of ESCC (P = 0.009). Kaplan-Meier analyses showed that patients with high TRIP13 expression had poor overall survival (P = 0.0022). Multivariate analysis indicated that TRIP13 expression might be an independent prognostic factor in ESCC patients (HR, 1.778, 95% confidence interval = 0.959-3.296, P = 0.028). Furthermore, downregulating TRIP13 in EC109 cell significantly attenuated the cell proliferation and progression, possibly by ß-catenin regulated EMT pathway. Conclusions: Our study demonstrated that TRIP13 might be a tumor promoting factor in ESCC and a promising prognostic indicator for ESCC patient.

Biobanking of Fresh-Frozen Gastric Cancer Tissues: Impact of Long-Term Storage and Clinicopathological Variables on RNA Quality.

BACKGROUND: Molecular research is increasingly dependent on high-quality biobanked biospecimens. Preanalytical variables in tissue processing and preservation may influence the RNA quality and research results. Hence, the effect of long-term storage and clinicopathological parameters on RNA quality needs to be elucidated. METHODS: Ninety gastric cancer tissue samples were collected and fresh-frozen in a -80°C freezer for 12 years (2006-2017). The histology was assessed and RNA integrity number (RIN) was detected by an Agilent 2100 Bioanalyzer. The impact of storage duration on RNA integrity and histomorphology was analyzed. The difference between RIN values and clinical variables was analyzed. Correlations between pathological parameters such as tumor cell percentage, stroma percentage, necrosis extent, cellularity, and RIN were assessed, respectively. RESULTS: Long-term storage at -80°C for 12 years did not adversely affect RNA integrity and histomorphology. RNA integrity was also not influenced by tumor location, estimated blood loss, cold/warm ischemia time, and surgical approach. However, RIN values were significantly correlated with the tumor cell percentage and stroma percentage. Gastric cancer tissues with higher tumor cell percentage or lower stroma percentage had higher RIN values. CONCLUSIONS: RNA quality of fresh-frozen gastric cancer tissues is influenced by clinical and histological parameters. Standard tissue collection procedure and histological quality control remain essential for tissue biobanking.

Association Between Genetic Polymorphisms of WNT1 Inducible Signaling Pathway Protein 1 and Uterine Cervical Cancer.

To date, no study has investigated the involvement of the single-nucleotide polymorphisms (SNPs) of WNT1 inducible signaling pathway protein 1 (WISP1) in uterine cervical cancer. Therefore, we conducted this study to explore the clinical implications of WISP1 SNPs in cervical cancer. One hundred and fifteen patients with invasive cervical cancer, 95 patients with preinvasive lesions, and 316 normal controls were enrolled. The WISP1 SNPs rs62514004, rs2929973, rs2977530, and rs2977537 were selected, and their genotypic distributions were determined through real-time polymerase chain reaction. Our findings showed that genotypes AG/GG in WISP1 SNP rs2977530 reduced the risk of invasive cervical cancer with AA as a reference; however, these genotypes did not reduce the risk of preinvasive lesions. By contrast, genotype AA in WISP1 SNP rs2977537 elevated the risk of invasive cervical cancer with GG/GA as a reference, but it did not elevate the risk of preinvasive lesions. Moreover, an additional integrated in silico analysis indicated that WISP1 rs2977537 altered the WISP1 expression recorded in the Genotype-Tissue Expression database. In conclusion, genotypes AG/GG in WISP1 SNP rs2977530 reduce the susceptibility of Taiwanese women to invasive cervical cancer, whereas genotype AA in rs2977537 increases the said risk.

The correlation of CD19 + CD24 + CD38 + B cells and other clinicopathological variables with the proportion of circulating Tregs in breast cancer patients.

BACKGROUND: T regulatory cells (Tregs) are known to negatively control immune response. The frequency of these cells was inversely correlated with clinical outcomes of breast cancer. CD19+CD24hiCD38hi cells also play a critical role in inflammation and autoimmune disease. However, their function in tumor immune response is less studied. In this study we aimed to determine the role of CD19+CD24hiCD38hi cells and some other clinicopathological variables in increasing the proportion of Tregs in breast cancer patients. METHODS: We selected 47 patients with invasive ductal breast carcinoma and 50 healthy controls and obtained their blood samples. RESULTS: The proportion of circulating CD4+CD25+Foxp3+ Tregs and CD19+CD24hiCD38hi cells was significantly increased in breast cancer patients. We also found that increased proportion of Tregs in breast cancer is correlated with HER2 amplification, advanced clinical stages, serum TGF-ß1 and increased CD19+CD24hiCD38hi cells in the peripheral blood. CONCLUSION: Altogether, our data suggest that as much as Tregs, CD19+CD24hiCD38hi B cells could also have a part in the suppression of immune response in breast cancer.

Correlation of Expression of CD44, p53 and bcl-2 Protein, DNA Ploidy Pattern, and Clinicopathologic Prognostic Factors in Invasive Ductal Carcinoma of the Breast

In this study of 64 cases of breast cancer with a clinical follow-up period of more than 5 years, several prognostic factors were evaluated. The purpose of this study was to determine whether any one parameter or group of parameters serves as adequate predictors of tumor behavior and patient's prognosis. Several prognostic factors included clinicopathological variables (patient's age, histologic grade, status of lymph node (LN) metastasis, and tumor size), expression of estrogen receptor (ER), progesterone receptor (PR), p53, bcl-2 and CD44 by immunohistochemistry, and DNA ploidy pattern. The results showed that the expression of ER and PR had a significant inverse correlation with the histologic grade (ER, p=0.05; PR, p<0.05). The expression of p53 protein showed a significant relationship with high histologic grade of tumor (p<0.05). The expression of bcl-2 protein was preferably seen in low histologic grade of tumor (p<0.05) and significantly associated with ER positive or PR positive tumors (ER, p<0.05; PR, p<0.05). This results suggest that bcl-2 protein might play significant roles in ER and PR. The CD44 expression showed a significant relationship with tumor size (p<0.05). The large size and aneuploidy pattern of tumor had a tendency to be associated with shorter patient survival. Cox's multivariate analysis showed that overall survival was affected by LN metastasis because of the shorter survival in patients with LN metastasis. In conclusion, tumor size, DNA ploidy pattern, and LN metastasis were themselves significant predictors of breast cancer survival rate.

Significance of Expression of p16, Cyclin D1, Rb, and p53 Protein and Correlation with Clinicopathologic Prognostic Factors in Invasive Ductal Carcinoma of the Breast

The retinoblastoma (Rb)/cyclin D1/p16 pathway is an important constituent of cell cycle regulation. Perturbations in this pathway due to a variety of genetic aberrations have been reported in many human cancers including breast cancer. We examined the significance of immunoexpression of p16 protein, cyclin D1 protein, Rb protein (pRb), and p53 protein in 128 cases of invasive breast carcinoma. The results were correlated with survival rate and clinicopathological variables, including age, histologic grade, lymph node status, tumor size, estrogen receptor (ER), and progesterone receptor (PR) content. Abnormal expressions of p16 and pRb which were defined as negative staining were seen in 21% and 43% of tumors, respectively. There was a significant inverse relationship between p16 and pRb expression. There was no correlation between p16 staining and any other parameters, including survival rate, cyclin D1, p53, and clinicopathologic variables. Surprisingly, there was a trend for tumors which were positive for pRb to be grade III ductal carcinomas. Cyclin D1 positivity was noted in 46% of cases. The expression of cyclin D1 protein was significantly higher in lower histologic grade, higher ER and PR expression. The expression of p53 protein showed a significant correlation with high tumor grade. In a Cox multivariate analysis, neither p16, pRb, cyclin D1 nor p53 was an independent predictor, but tumor size and lymph node status were independent predictors of patient outcome.