ALDH2 as an immunological and prognostic biomarker: Insights from pan-cancer analysis.

Aldehyde dehydrogenase 2 (ALDH2) plays a critical role in safeguarding cells against acetaldehyde toxicity and is closely linked to human metabolism. Nevertheless, the involvement of ALDH2 in cancer remains enigmatic. This investigation seeks to comprehensively assess ALDH2's significance in pan-cancer. We conducted an all-encompassing analysis of pan-cancer utilizing multiple databases, including TCGA, linkedomicshs, UALCAN, and Kaplan-Meier plotter. We employed diverse algorithms such as EPIC, MCPCOUNTER, TIDTIMER, xCell, MCP-counter, CIBERSORT, quanTIseq, and EPIC to examine the connection between ALDH2 expression and immune cell infiltration. Single-cell sequencing analysis furnished insights into ALDH2's functional status in pan-cancer. Immunohistochemical staining was performed to validate ALDH2 expression in cancer tissues. In a comprehensive assessment, we observed that tumor tissues demonstrated diminished ALDH2 expression levels compared to normal tissues across 16 different cancer types. ALDH2 expression exhibited a significant positive correlation with the infiltration of immune cells, including CD4 + T cells, CD8 + T cells, neutrophils, B cells, and macrophages, in various tumor types. Moreover, this study explored the association between ALDH2 and patient survival, examined the methylation patterns of ALDH2 in normal and primary tumor tissues, and delved into genetic variations and mutations of ALDH2 in tumors. The findings suggest that ALDH2 could serve as a valuable prognostic biomarker in pan-cancer, closely linked to the tumor's immune microenvironment.

Expression and significance of effector proteins NLRP3 and gasdermin D N-terminal protein in the pyrolysis pathway in breast cancer.

OBJECTIVES: To detect the expression and significance of GSDMD-N (gasdermin D N-terminal) in breast cancer, along with pyroptosis effector protein NLRP3 (nucleotide-binding oligomerization domain-like receptor protein 3), and determine their relationship with the clinicopathological characteristics of breast cancer. METHODS: From January 2014 to December 2014, NLRP3 and GSDMD-N expression in 90 breast carcinoma organism samples and 30 paracancer tissues in the Department of Pathology. The First Affiliated Hospital of Bengbu Medical College was assessed using immunohistochemistry. The method of Kaplan-Meier was employed for the sake of comparing the survival between NLRP3 and GSDMD-N protein low and high expression groups. Among the breast cancerous organisms, the relationship between the expression of NLRP3 and GSDMD-N, corresponding adjacent tissues, and various clinicopathological features was analyzed using the χ2 and Spearman rank correlation tests. RESULTS: In the 90 breast cancer tissue samples, the pyrolysis pathway effector proteins GSDMD-N and NLRP3 were actively associated; and, expression intensities of NLRP3 and GSDMD-N were shown to be correlated with breast cancer. In addition, the clinicopathological features of patients were shown to be correlated with breast cancer. Notably, the higher the expressions of NLRP3 and GSDMD-N, the lower the risk of death of patients with breast cancer and the better the prognosis. CONCLUSION: The expression of the pyrolysis effector proteins NLRP3 and GSDMD-N in breast cancer tissues may take the lead in tumor prognosis in patients with breast cancer.

Expression levels of caspase-3 and gasdermin E and their involvement in the occurrence and prognosis of lung cancer.

BACKGROUND: Pyroptosis plays a dual role in the development of cancer and malignancy; as such, it may potentially be a new target for cancer treatment. However, the inflammatory response to pyroptosis may have adverse effects on the body. The roles of gasdermin E (GSDME), caspases, and related proteins associated with pyroptosis in cancer remain controversial. AIM: The goal of this study was to determine whether the expression levels of caspase-3 and GSDME affect the clinical stage, pathological grade, or survival prognosis of patients with lung cancer. METHODS: We examined the protein levels of GSDME, caspase-3, caspase-8, and caspase-9 in lung tissue samples from 100 patients with lung cancer by using immunohistochemistry. RESULTS: We found that GSDME, caspase-3, and caspase-8 were more highly expressed in tumor tissues than in adjacent normal tissues. Moreover, we found that GSDME could serve as a prognostic factor as there was a positive correlation between its expression level and the postoperative survival rate of patients with lung cancer. CONCLUSIONS: GSDME may be an independent factor affecting the prognosis of patients with lung cancer. However, the role of GSDME and its related proteins in cancer requires further research.

Expression of KAI1 and AGR2 in lung adenocarcinoma and their clinicopathological significance.

OBJECTIVE: Anticancer 1 (KAI1, tumor metastasis suppressor gene) and Anterior gradient-2 (AGR2, considered a valuable prognostic factor for some cancers) are associated with metastasis and prognosis of various types of human cancers. Nevertheless, the relationship between KAI1 and AGR2 in lung adenocarcinoma (LUAD) remains unclear. In this research, we analyzed the correlations between KAI1 and AGR2 in LUAD, and explored their correlations with clinicopathological parameters and overall survival time (OS) in patients with LUAD. METHODS: Immunohistochemical staining was used to detect KAI1 and AGR2 expression in 132 cases of LUAD samples. At the same time, all clinicopathological parameters and postoperative survival information were collected. RESULTS: AGR2 positive rate was significantly increased and KAI1 positive rate was significantly decreased in LUAD and control tissues. KAI1 positive rates were negatively correlated with tumor stage, LNM stage and TNM stage, and KAI1 subgroup positive expression of OS was significantly higher than negative KAI1 subgroup. The positive rate of AGR2 was positively correlated with tumor grade, LNM stage and TNM stage, and negatively correlated with patients OS. Active expression of AGR2 and KAI1, tumor stage, and LNM stage in multivariate analyses may be independent prognostic factors for OS in LUAD patients. CONCLUSION: KAI1 and AGR2 may be potential biomarkers for prognosis and metastasis, and they are also promising therapeutic targets for LUAD patients.

Role of Cytokines Released During Pyroptosis in Non-Small Cell Lung Cancer.

PURPOSE: Pyroptosis is a recently discovered highly inflammatory form of programmed cell death, during which the N-terminus of the cleaved Gasdermin protein family forms pores in the cell membrane, leading to cell disintegration and the release of certain intracellular factors, including caspase3, gasdermin E (GSDME), and high mobility group proteins (HMGB1), which trigger a series of secondary inflammatory reactions. Specifically, caspase3 can lyse GSDME and induce pyrolysis, while HMGB1 is released passively after cell membrane destruction. In this study, the roles of these proteins in lung cancer tissues as well as their clinical significance were investigated. PATIENTS AND METHODS: The expression levels of GSDME, caspase3, and HMGB1 proteins in lung cancer and paracancerous tissues were determined via immunohistochemical staining, and their relationship with the clinical stage, pathological grade, and survival prognosis of the patients was analyzed. Further, CD8+ T cell accumulation in the above-mentioned tissues was also determined, and differences between them with respect to CD8+T cell distribution were also investigated. Furthermore, the relationships between CD8+ T cell abundance and the expression levels of the above-mentioned proteins were determined via statistical analyses. RESULTS: Lung cancer and paracancerous tissues showed significantly different GSDME, caspase3, and HMGB1 protein expression levels. GSDME expression level and the presence or absence of lymph node invasion were identified as prognostic indicators of survival in patients with lung cancer. Surprisingly, however, HMGB1, which showed a certain level of correlation with the presence or absence of lymph node metastasis, could not be used as a prognostic indicator of survival. CONCLUSION: GSDME may be an important prognostic indicator of survival in patients with lung cancer. However, the effects of HMGB1 expression level and CD8+ T cell abundance on the prognosis of patients with lung cancer still need further investigation.

Fibroblast Activation Protein-α Expressing Fibroblasts Promote Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma.

BACKGROUND AND OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) remains one of the most common malignancies in China and has a high metastasis rate and poor prognosis. Fibroblast activation protein-α (FAP-α) is a serine peptidase the expression of which in cancer-associated fibroblasts has been associated with a higher risk of metastases and poor survival. This study aimed to analyze the correlation of FAP-α expression with the lymph node metastasis and prognostic significance in ESCC. METHODS: FAP-α expression was examined in 121 resected ESCC specimens and 10 adjacent normal tissue using immunohistochemistry. FAP-α expression was scored in the stromal fibroblasts adjacent to neoplastic nests. A chi-square test was used to analyze the correlation between FAP-α expression in tumors stromal and lymph node metastasis of ESCC. The association between FAP-α expression and prognosis was evaluated using univariable and multivariable statistical modeling. RESULTS: FAP-α expression was absent in the benign controls. FAP-α expression was evident in the stromal 37% (45/121) of ESCC. Expression of FAP-α level is significantly associated with lymph node metastasis (p=0.023), but it is not correlated to age, gender, and tumor location in ESCC patients. Stromal FAP-α expression was significantly associated with poor survival in univariable (HR 2.009; 95% CI 1.259-3.205; p=0.003) and multivariable analysis (HR 1.833; 95% CI 1.144-2.937; p=0.012). CONCLUSION: FAP-α may be an important regulator in lymph node metastasis of ESCC and may provide a novel therapeutic target in ESCC.

Upregulation of FHIT gene expression in endometrial carcinoma by RNA activation.

Endometrial carcinoma is the most common malignant tumors of the reproductive system, and fragile histidine triad (FHIT) plays an important role in multiple tumors. The purpose of this study was to investigate the expression of FHIT gene in endometrial carcinoma, and its effect on proliferation, invasion, and metastasis after upregulation. In vitro, the endometrial carcinoma cell lines were cultured. The FHIT-saRNA expression vector was constructed. The endometrial carcinoma cell line that upregulated the expression of FHIT was established, and whether the saRNA had a direct targeting regulation on the FHIT was verified. A difference of expression of FHIT in normal endometrial and endometrial carcinoma was detected. We detected the proliferation of endometrial carcinoma cell lines before and after activating FHIT. The endometrial carcinoma cell lines were compared with the corresponding transiently transfected cell lines in their capabilities of cell migration and invasion. The results showed that the expression of FHIT in endometrial carcinoma was significantly decreased or even deficient compared with normal endometrium. Upregulating the expression of FHIT is related to inhibiting the proliferation, invasion and metastasis of endometrial carcinoma. The possible mechanism is related to the regulation of cell cycle regulation, and plays a role in inhibiting tumor proliferation. The research on molecular mechanism in the development and progression of endometrial carcinoma has important theoretical significance for improving the diagnosis, treatment and prognosis of clinical tumors.

Clinicopathologic features of succinate dehydrogenase deficiencient renal cell carcinoma.

According to the WHO new renal tumor classification (2016), the clinical and pathologic characteristics, immunophenotype and molecular genetic characteristics of 2 cases of succinate dehydrogenase (SDH)-deficient renal cell carcinoma were retrospectively analyzed, and the relevant literature was reviewed. In 2 cases, there was 1 male and 1 female, the average age was 52.5 years old. The renal tumor average length was 4.2 cm. Tumor cut surface was solid, grayish yellow and soft. The tumor boundary was clear, and the cells were arranged in solid, nested, or small tubular growth. The cytoplasm was vacuolated or contained eosinophilic or light-stained flocculent substance, with a regular nucleus and no obvious nucleoli, showing low-grade nuclei. No atypical mitotic figures or necrosis were found. SDH-deficient renal cell carcinoma has a characteristic morphologic manifestation, and lack of SDHB expression in the immunophenotype. During the clinical diagnosis and treatment, the patient's condition and family genetic history should be asked for in detail, and genetic detection should be performed to confirm the diagnosis if necessary.

Detection of proteins associated with the pyroptosis signaling pathway in breast cancer tissues and their significance.

OBJECTIVE: To study the expression of pyroptosis signaling pathway related proteins in breast cancer tissues and paracancer tissues, analyze their relationship with breast cancer clinicopathologic features, and explore their relationship to prognosis. METHODS: Immunohistochemistry ElivisionTM plus was used to detect the expression of caspase-1, IL-1ß and Gasdermin-D (GSDMD) in 108 cases of breast cancer and 23 cases of benign lesions adjacent to breast cancer. RESULTS: Using 108 cases of breast cancer and 23 cases of para-cancerous benign tissues, the pyroptosis signaling pathway effector proteins caspase-1, IL-1ß, and GSDMD were positively correlated with each other. The higher the expression level, the lower the histophologic grade of breast cancer, the smaller the tumor size, the lower the clinical stage, the lower the possibility of lymph node metastasis, the lower the risk of death, and the better the prognosis. CONCLUSIONS: Pyroptosis signaling pathway effectors caspase-1, IL-1ß and GSDMD expression may play an important role in the invasion, metastasis, and prognosis of breast cancer.

Observation of tumor-associated macrophages expression in gastric cancer and its clinical pathological relationship.

The present study was designed to investigate the expression of tumor-associated macrophages (TAMs) in gastric cancer and its clinicopathological relationship. In addition, we also aimed to analyze the relationship between helicobacter pylori (HP) infection and TAMs in gastric cancer.The protein expression of CD16 and CD163 in 90 gastric cancer tissues and 30 margin tissues was detected by immunohistochemistry. HP infection was detected in 90 gastric cancer tissues and 30 margin tissues by gram staining and immunohistochemistry.There was no clear correlation between CD16 macrophages and gastric cancer. The density of CD163 macrophages was not correlated with the general condition of tumor patients, but with tumor size, tumor differentiation, lymphatic metastasis, depth of invasion and TNM stage. Additionally, the infection rate of HP in gastric cancer tissues was significantly higher.In summary, TAMs are associated with tumor size, degree of differentiation, depth of invasion, lymph node metastasis and TNM stage, suggesting their critical role in the invasion and metastasis of gastric cancer.

Prenatal exposure of staphylococcal enterotoxin B attenuates the development and function of blood regulatory T cells to repeated staphylococcal enterotoxin B exposure in adult offspring rats.

Introduction. Staphylococcal enterotoxin B (SEB) is an extensively studied super-antigen. A previous study by us suggested that SEB exposure during pregnancy could alter the percentage of CD4+ and CD8+ T cells in the peripheral blood of neonatal offspring rats.Aim. It is unknown whether SEB exposure during pregnancy can influence the development of regulatory T cells (Tregs) in the peripheral blood of neonatal offspring rats.Methodology. Pregnant rats at gestational day 16 were intravenously injected with 15 µg SEB. Peripheral blood was acquired from neonatal offspring rats on days 1, 3 and 5 after delivery and from adult offspring rats for determination of Treg number by cytometry, cytokines by ELISA, and FoxP3 expression by real-time PCR and western blot.Results. SEB given to pregnant rats significantly increased the absolute number of Tregs and the expression levels of FoxP3, IL-10 and TGF-ß (P<0.05, P<0.01) in the peripheral blood of not only neonatal but also adult offspring rats. Furthermore, repeated SEB exposure in adult offspring rats significantly decreased the absolute number of Tregs (P<0.01), and the expression levels of FoxP3, IL-10 and TGF-ß (P<0.05, P<0.01) in their peripheral blood.Conclusion. Prenatal SEB exposure attenuates the development and function of Tregs to repeated SEB exposure in the peripheral blood of adult offspring rats.

Expression of combined interference of slug and FoxC2 in endometrial carcinoma and its clinicopathological relationship.

BACKGROUND: Endometrial carcinoma is one of the three major malignant tumors in female reproductive system. The current research aimed to investigate the relationship between the Slug and FoxC2 expression and the proliferation, invasion and metastasis of endometrial carcinoma. METHODS: The expression of Slug and FoxC2 genes between 124 endometrial carcinoma tissues and 35 normal endometrial tissues was analyzed through immunohistochemistry. The endometrial carcinoma cell lines Ishikawa and RL-952 were cultured, the Slug-shRNA and FoxC2-shRNA expression vectors were constructed, and the endometrial carcinoma cells interfering with the expression of Slug and FoxC2 genes were also established. Western blotting and RT-PCR were employed to verify whether shRNA could down regulate the expression of Slug and FoxC2 genes. Additionally, the proliferation, migration and invasion capacities in both cell lines after interfering with Slug and FoxC2 was detected through CCK-8 and Transwell assay respectively. Furthermore, MMP2 and MMP9 were detected by ELISA and epithelial-mesenchymal transition (EMT) related proteins including E-cadherin, N-cadherin and Vimentin were assessed by Western blotting analysis. RESULTS: Compared with normal endometrial tissues, the Slug and FoxC2 expression levels in endometrial carcinoma tissues were remarkably increased. shRNAs transfection significantly down-regulated expressions in both endometrial carcinoma cell lines. The proliferation, invasion and migration ability were significantly inhibited by Slug-shRNA and FoxC2-shRNA compared with the control group. The expression of E-cadherin was increased while the expression of N-cadherin, Vimentin, MMP-2 and MMP-9 was suppressed by the Slug-shRNA and FoxC2-shRNA. CONCLUSIONS: Slug and FoxC2 could be used as a prognostic factor of endometrial carcinoma. Interfering with the expression of Slug and FoxC2 in endometrial carcinoma cell lines could effectively inhibit the proliferation, invasion and migration, and its mechanism is related to the inhibition of EMT. Slug and FoxC2 are potential targets for the treatment of endometrial carcinoma.

Prognostic implications of autophagy-associated gene signatures in non-small cell lung cancer.

Autophagy, a highly conserved cellular proteolysis process, has been involved in non-small cell lung cancer (NSCLC). We tried to develop a prognostic prediction model for NSCLC patients based on the expression profiles of autophagy-associated genes. Univariate Cox regression analysis was used to determine autophagy-associated genes significantly correlated with overall survival (OS) of the TCGA lung cancer cohort. LASSO regression was performed to build multiple-gene prognostic signatures. We found that the 22-gene and 11-gene signatures could dichotomize patients with significantly different OS and independently predict the OS in TCGA lung adenocarcinoma (HR=2.801, 95% CI=2.252-3.486, P<0.001) and squamous cell carcinoma (HR=1.105, 95% CI=1.067-1.145, P<0.001), respectively. The prognostic performance of the 22-gene signature was validated in four GEO lung cancer cohorts. Moreover, GO, KEGG, and GSEA analyses unveiled several fundamental signaling pathways and cellular processes associated with the 22-gene signature in lung adenocarcinoma. We also constructed a clinical nomogram with a concordance index of 0.71 to predict the survival possibility of NSCLC patients by integrating clinical characteristics and the autophagy gene signature. The calibration curves substantiated fine concordance between nomogram prediction and actual observation. Overall, we constructed and verified a novel autophagy-associated gene signature that could improve the individualized outcome prediction in NSCLC.

Ectopic thymoma: report of 2 cases and review of the literature.

In this report, we present two cases of ectopic thymoma, aiming to explore the clinicopathologic features, diagnosis, and differential diagnosis of ectopic thymoma. Case 1 was a female 56-years-old. For 6 months' time, there was no obvious cause of cough, expectoration, chest tightness, or asthma with chest pain. PET-CT showed a right middle lung and lower lung mass with increased FDG metabolism. Postoperative pathology was diagnosed as right middle and lower lung ectopic thymoma, type B2, invading the chest wall. Case 2 was a male of 54-years-old. By physical examination the right chest cavity had a mass present for 1 week and he was admitted to hospital. Postoperative pathology was diagnosed as right thoracic ectopic thymoma, type AB. No recurrence has been found to in the follow-up of these two patients. In conclusion, ectopic thymoma occurs outside the anterior mediastinum. It is rare, the clinical symptoms are not typical, and pre-operative diagnosis is difficult. It is easily misdiagnosed as other diseases. Surgical treatment is the best method. According to the pathologic type and invasion of the tumor, radiotherapy may be considered.

The intervention research on treatment by Xianchen to rabbits model of chemotherapeutic phlebitis.

PURPOSE: To develop a chemotherapeutics induced phlebitis and explore the effects of Xianchen on the phlebitis treatment. METHODS: Forty-eight rabbits were divided into two series. Phlebitis model induced by vincristine was established at each series. The first series had 24 rabbits, which were divided into four groups (6 hours, 12 hours, 18 hours, 24 hours) after vincristine infusion. The grades of phlebitis through visual observation and histopathological examination were observed. The second series had also 24 rabbits. Interventions were performed 12 hours after vincristine infusion. These rabbits were randomly divided into four groups, according to treatment: Hirudoid (bid), Xianchen (daily), Xianchen (tid), Xianchen (five times a day). Four days after intervention, the venous injury through visual observation and histopathological examination were evaluated. RESULTS: Series 1: Phlebitis appeared 12 hours after infusion of vincristine through visual observation. There was a significant difference (p<0.05) between 6 hours and 24 hours, 6 hours and 18 hours through visual observation. However, the inflammation happened 6 hours after infusion, the loss of venous endothelial cells demonstrated differences among four groups through histopathological evaluation (p<0.05). There were significant differences (p<0.05) after 4 days among the intervention groups through visual observation, the effects of Xianchen group (five times a day) were better than Xianchen group (tid) (p<0.01). The treatment of edema demonstrated differences among groups through histopathological evaluation (p<0.05), Xianchen (five times a day) better relieved the degree of edema (p<0.05). CONCLUSIONS: The study showed that inflammatory reaction of phlebitis appeared early. Xianchen can treat vincristine induced phlebitis, as well as Hirudoid. It is particularly effective in the treatment of edema, and there is a remarkable dose-response relationship.

The intervention research on treatment by Xianchen to rabbits model of chemotherapeutic phlebitis

ABSTRACT PURPOSE: To develop a chemotherapeutics induced phlebitis and explore the effects of Xianchen on the phlebitis treatment. METHODS: Forty-eight rabbits were divided into two series. Phlebitis model induced by vincristine was established at each series. The first series had 24 rabbits, which were divided into four groups (6 hours, 12 hours, 18 hours, 24 hours) after vincristine infusion. The grades of phlebitis through visual observation and histopathological examination were observed. The second series had also 24 rabbits. Interventions were performed 12 hours after vincristine infusion. These rabbits were randomly divided into four groups, according to treatment: Hirudoid (bid), Xianchen (daily), Xianchen (tid), Xianchen (five times a day). Four days after intervention, the venous injury through visual observation and histopathological examination were evaluated. RESULTS: Series 1: Phlebitis appeared 12 hours after infusion of vincristine through visual observation. There was a significant difference (p<0.05) between 6 hours and 24 hours, 6 hours and 18 hours through visual observation. However, the inflammation happened 6 hours after infusion, the loss of venous endothelial cells demonstrated differences among four groups through histopathological evaluation (p<0.05). There were significant differences (p<0.05) after 4 days among the intervention groups through visual observation, the effects of Xianchen group (five times a day) were better than Xianchen group (tid) (p<0.01). The treatment of edema demonstrated differences among groups through histopathological evaluation (p<0.05), Xianchen (five times a day) better relieved the degree of edema (p<0.05). CONCLUSIONS: The study showed that inflammatory reaction of phlebitis appeared early. Xianchen can treat vincristine induced phlebitis, as well as Hirudoid. It is particularly effective in the treatment of edema, and there is a remarkable dose-response relationship.

Extrapancreatic solid pseudopapillary tumors: A clinicopathological analysis of two cases.

Solid pseudopapillary tumors (SPTs) are unusual neoplasms that mostly occur in the pancreas, and predominantly affect young women. As a low-grade malignant neoplasm of the exocrine pancreas, they occasionally metastasize, usually to the liver or peritoneum. It has been reported that <1% of SPTs are primary extrapancreatic SPTs. In the present study, we present two rare, but conspicuous extrapancreatic SPTs. Both occurred in young women, and showed good prognoses following surgery. One was a recurrent SPT of the pancreas that metastasized to the ovary, and the other was a distinct primary neoplasm that arose in the retroperitoneal area. The pathological features of the two tumors, including solid and pseudopapillary growth patterns with pale or eosinophilic cytoplasm, were characteristic of SPTs of the pancreas. However, in the case of the metastatic ovarian tumor, focal necrosis and an increased nuclear-to-cytoplasmic ratio were observed. The presence of positive nuclear-cytoplasmic ß-catenin, the loss of membranous E-cadherin expression, and a perinuclear punctate CD99 staining pattern on immunohistochemistical analysis, were essential features for diagnosis. The aim of the present study was to compare the morphological and immunohistochemical features of these tumors with those typical of pancreatic SPTs, and to raise awareness that SPTs are able to metastasize to unusual sites, and may also arise as primary tumors outside the pancreas, which may lead to diagnostic dilemmas.