Survival and clinicopathological significance of blood vessel invasion in operable breast cancer: a systematic review and meta-analysis.

BACKGROUND: Lymphovascular invasion, including lymphatic-vessel invasion and blood-vessel invasion, plays an important role in distant metastases. The metastatic pattern of blood-vessel invasion may differ from that of lymphatic-vessel invasion. However, its prognostic significance in breast cancer remains controversial. We evaluated the role of blood-vessel invasion in the prognosis of operable breast-cancer patients and its association with clinicopathological characteristics. METHODS: We systematically searched EMBASE, PubMed, the Cochrane Library and Web of Science for studies in English through December 2020. Disease-free survival, overall survival and cancer-specific survival were the primary outcomes. Pooled hazard ratios and 95% confidence intervals were assessed using a random-effects model. RESULTS: Twenty-seven studies involving 7954 patients were included. Blood-vessel invasion occurred in 20.4% of tumor samples. Pooled results showed significant associations of blood-vessel invasion with worse disease-free survival (hazard ratio = 1.82; 95% confidence interval = 1.43-2.31) and overall survival (hazard ratio = 1.86; 95% confidence interval = 1.16-2.99) in multivariate analyses. The results of the univariate analyses were similar. Among the clinicopathological factors, blood-vessel invasion was associated with larger tumor size, lymph-node metastasis, nonspecific invasive type, higher histological grade, estrogen receptor-negative breast cancer, human epidermal growth factor receptor 2-positive breast cancer and lymphatic-vessel invasion. In the lymph-node-negative subgroup analyses, the presence of blood-vessel invasion led to poorer disease-free survival (hazard ratio = 2.46; 95%confidence interval = 1.64-3.70) and overall survival (hazard ratio = 2.94; 95%confidence interval = 1.80-4.80). CONCLUSIONS: We concluded that blood-vessel invasion is an independent predictor of poor prognosis in operable breast cancer and is associated with aggressive clinicopathological features. Breast-cancer patients with blood-vessel invasion require more aggressive treatments after surgery.

Clinicopathological significance of TUBB3 in upper tract urothelial carcinoma and possible application in urine cytology.

ßIII-Tubulin, encoded by the TUBB3 gene, is a microtubule protein. We previously reported that TUBB3 is overexpressed in renal cell carcinoma. We investigated the clinicopathological significance of TUBB3 in upper tract urothelial carcinoma (UTUC) by immunohistochemistry. In normal tissue, TUBB3 expression was weak or absent. In contrast, TUBB3 overexpression was observed in urothelial carcinoma (UC) tissues in 51 (49%) of 103 UTUC cases. TUBB3 overexpression was associated with nodular/flat morphology, high-grade disease, high T stage, and a poor prognosis. Similar results were obtained in The Cancer Genome Atlas bladder cancer cohort. TUBB3 expression was also associated with high Ki-67 labeling index, CD44v9, HER2, EGFR, and p53 expression in UTUC. Among representative cancer-related molecules, TUBB3 was an independent predictor of progression-free survival and high-grade UC. Finally, using urine cytology samples, we analyzed TUBB3 expression by immunocytochemistry. TUBB3 expression was more frequently found in UC cells than in nonneoplastic cells. The diagnostic accuracy of urine cytology was improved when combined with TUBB3 immunostaining. The findings suggest the importance of TUBB3 in tumor progression and its potential application as a biomarker for high-grade disease and the prognosis of UC. Moreover, combination with TUBB3 immunostaining might improve the diagnostic accuracy of urine cytology.

CRM1 expression: association with high prognostic value in laryngeal cancer.

BACKGROUND: Laryngeal cancer is a very common malignant tumor of the head and neck. While laryngeal cancer does not show any obvious early symptoms, it tends to have a poor prognosis in advanced clinical stages. Chromosome region maintenance 1 (CRM1) mediates the nuclear export of some RNAs, major and tumor suppressor proteins and has been associated with the pathogenesis of many tumors. However, the clinicopathological significance of CRM1 gene expression in laryngeal cancer has not been clarified yet. Therefore, this study aims to detect the expression of CRM1 in laryngeal cancer and to investigate its relationship with clinicopathological parameters and prognosis. METHODS: CRM1 expression in matched tumor and normal tissues obtained from 43 laryngeal cancer patients were evaluated intracellular for protein and mRNA levels by immunohistochemical staining (IHC), western-blot, and quantitative real-time RT-PCR (qRT-PCR), respectively. RESULTS: IHC, western-blot, and qRT-PCR analyses showed that CRM1 expression was significantly increased in laryngeal cancer tissue compared to normal tissue. Increased expression of CRM1 has been associated with poor prognostic clinicopathological features, including advanced tumor stage, increased tumor invasion, larger tumor size, positive lymph node metastasis, distant metastasis, and invasive histological type by IHC, western-blot, and qRT-PCR. Kaplan-Meier survival analysis showed that patients with high expression of CRM1 exhibited lower overall survival compared to those with low expression (Log-rank = 7.16, p = 0.007). According to the The Cancer Genome Atlas (TCGA) datasets, elevated CRM1 expression in head and neck cancer including cases of squamous cell laryngeal origin is associated with advanced tumor stage and histological grade (p > 0.05, for all). DISCUSSION: Consequently, CRM1 plays an important role in laryngeal cancer and may serve as an indicator and prognostic factor for poor overall survival in laryngeal cancer patients.

Prognostic and clinicopathological significance of transcription factor c-Jun in hypopharyngeal squamous cell carcinoma: a 3-year follow-up retrospective study.

PURPOSE: To investigate the expression and prognostic value of c-Jun in hypopharyngeal squamous cell carcinoma (HPSCC). METHODS: A retrospective study was performed on a cohort of 99 HPSCC patients. The expression of c-Jun and phosphorylated-c-Jun (p-c-Jun) was evaluated via immunohistochemistry (IHC) staining. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier method and multivariate Cox regression analysis. RESULTS: The high expression of c-Jun and p-c-Jun in HPSCC accounted for 60.61% and 16.16%, respectively. High expression of c-Jun was closely associated with cT stage (p = 0.0401), tumor size (p = 0.0276), number of lymph node metastases (p = 0.0205) and pathological differentiation (p = 0.0108). The expression of c-Junhigh (p = 0.0043), p-c-Junhigh (p = 0.0376) and c-Junhigh/p-c-Junhigh were closely associated with poor OS. The Cox proportional multivariate hazard model revealed that lymphovascular invasion and c-Jun expression were independent influencing factors of OS in HPSCC patients. CONCLUSION: Our findings suggest that c-Jun is a reliable prognostic factors in HPSCC patients.

Clinicopathological significance of the overexpression of MUC1 in upper tract urothelial carcinoma and possible application as a diagnostic marker.

Mucin 1 (MUC1) overexpression has been reported in many malignancies and is associated with a poor prognosis. However, the clinicopathological significance of MUC1 in upper tract urothelial carcinoma (UTUC) has not been investigated. We analyzed the expression and distribution of MUC1 in UTUC by immunohistochemistry. In normal urothelium, MUC1 expression was observed on the surface of umbrella cells. Meanwhile, the strong expression of MUC1 was observed in cell membranes and cytoplasm in UTUC tissues, and it was detected in 64 (58%) of a total of 110 UTUC cases. MUC1-positive UTUC cases were associated with nodular/flat morphology, high grade, high T stage, and lymphatic and venous invasion and poor prognosis. Additionally, MUC1 expression was associated with high expression of Ki-67, programmed death-ligand 1 (PD-L1), CD44 variant 9 (CD44v9), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and p53 in UTUC. Furthermore, immunocytochemistry for MUC1 on urine cytology slides demonstrated that the strong staining of MUC1 was more frequently found in tumor cells than in nonneoplastic cells. The diagnostic accuracy of urine cytology was improved by combining MUC1 immunostaining with cytology. These results suggest that MUC1 may be a prognostic biomarker in UTUC, and MUC1 exression has a potential application as a diagnostic immunomarker for urine cytology.

Clinicopathological significance of HSP70 expression in gastric cancer: a systematic review and meta-analysis.

BACKGROUND: Heat shock protein 70 (HSP70) has been associated with the clinicopathological characteristics and prognosis of many cancers types, implying that it is a potential cancer biomarker. However, no consensus has been reached regarding its clinicopathological and prognostic significance in patients with gastric cancer. To address this gap, we performed a systematic review and meta-analysis. METHODS: We searched PubMed, Embase, and the Cochrane Library for full-text literature according to the eligibility criteria. We used the odds ratio and hazard ratio as the suitable parameters to evaluate the clinicopathological and prognostic significance of HSP70. The statistical analysis was performed using STATA 15.0. RESULTS: After inclusion and exclusion of studies based on the eligibility criteria, data of 1,307 patients with gastric cancer from 9 studies were finally included. The pooled outcomes implied that HSP70 expression was significantly correlated with higher differentiation degrees, intestinal gastric cancer, and lymphovascular invasion but not with age, gender, depth of invasion, Helicobacter pylori infection, lymph node invasion, TNM stages, and metastasis. The pooled HR showed no significant correlation between HSP70 expression and overall survival of gastric cancer patients. CONCLUSIONS: Our meta-analysis showed that HSP70 plays a complicated role in the development of gastric cancer. It may be directly engaged in tumour differentiation and distant invasion but cannot be considered a biomarker for predicting the prognosis of gastric cancer.

Expression of inositol polyphosphate 4-phosphatase type II and the prognosis of oral squamous cell carcinoma.

Inositol polyphosphate 4-phosphatase type II (INPP4B) is a phosphoinositide phosphatase that plays complex roles in the pathogenesis of different tumors. We aimed to explore the expression, clinicopathological significance, and prognostic value of INPP4B in oral squamous cell carcinoma (OSCC). Tissue microarrays that included samples from 176 primary OSCCs, 42 normal mucosae, and 69 dysplastic tissues were used for immunostaining analyses of INPP4B protein. Aperio ScanScope CS scanner and aperio quantification software were used to scan the microarrays and score the staining, respectively. We also evaluated the correlation between INPP4B expression and clinical parameters, pathological grades, node-positive status, and immune-related markers. Expression of INPP4B was statistically significantly upregulated in human primary OSCC tissues compared with dysplastic and normal tissues. Additionally, we found that patients with strong expression of INPP4B had a statistically significantly poorer overall survival than patients with weak expression of INPP4B. Furthermore, our study indicated that expression of INPP4B in OSCC was positively associated with expression of p-S6Ser235/236 , p-CADSer1859 , and certain immune checkpoints (B7-H4, Galectin-9). Therefore, INPP4B may be an independent prognostic indicator for patients with OSCC, in which it might function as an oncoprotein.

High prevalence of BRAF V600E mutations in Korean patients with ameloblastoma: Clinicopathological significance and correlation with epithelial-mesenchymal transition.

BACKGROUND: BRAF V600E mutations are activating mutations that have recently been detected in ameloblastoma. However, their prevalence has not been reported in East Asian patients with ameloblastoma and their clinicopathological significance remains unclear. In this study, we examined the prevalence and clinicopathological significance of BRAF V600E mutations in Korean patients with ameloblastoma. In addition, we investigated the relationship between BRAF V600E mutations and epithelial-mesenchymal transition, which has not been studied in ameloblastoma. METHODS: Thirty ameloblastoma tissue samples were collected, and DNA isolation, polymerase chain reaction, and Sanger sequencing were performed to detect BRAF V600E mutations. Immunohistochemistry was carried out using antibodies against two epithelial-mesenchymal transition-inducing transcription factors, Twist and Snail. Associations of BRAF V600E mutations with clinicopathological factors and expression of Twist and Snail were statistically analyzed. RESULTS: We found a high frequency (90.0%) of BRAF V600E mutations, and mutation status was not associated with clinicopathological factors including age, tumor location, and recurrence. Positive expression of Twist and Snail was observed in 33.3% and 56.7% of cases, respectively, and associated with recurrence (P = 0.020 and 0.010, respectively). There was no correlation between BRAF V600E mutation status and expression of Twist and Snail (P = 1.000, for both). CONCLUSIONS: A higher prevalence of BRAF V600E mutations was identified in Korean patients with ameloblastoma compared with previous studies, which indicates that BRAF-targeted therapies can be widely used for refractory ameloblastomas. Furthermore, our findings suggest that BRAF V600E mutations and epithelial-mesenchymal transition may act independently in the development of ameloblastoma.

Prognostic impact of tumor-associated macrophage infiltration in esophageal cancer: a meta-analysis.

Aim: To provide clarity surrounding the association between tumor-associated macrophages (TAMs) and esophageal cancer prognosis. Materials & methods: Several databases were searched. The meta-analysis was conducted by using software Stata 12.0 and Revman. Results: Sixteen studies were included in this analysis (2292 samples). CD68+ TAM density was not associated with overall survival (OS; hazard ratio [HR]: 0.88, 95% CI: 0.67-1.15; p = 0.33) and disease-free survival (HR: 1.25, 95% CI: 0.66-2.35; p = 0.49). M2-like TAMs were associated with poor overall survival (HR: 1.47, 95% CI: 1.10-1.98; p = 0.01), Tumor, Node, Metastasis staging and vessel metastasis. Conclusion: CD68+ TAM density is not associated with esophageal cancer progression, while CD163+ M2-like TAMs is a potential risk factor.

Abnormal nuclear expression of Pygopus-2 in human primary hepatocellular carcinoma correlates with a poor prognosis.

AIMS: Pygopus-2 (Pygo2) is a critical element of the canonical Wnt/ß-catenin transcriptional complex. The aim of the present study was to investigate the expression patterns and clinicopathological significance of Pygo2 in human primary hepatocellular carcinoma (HCC). METHODS AND RESULTS: Real-time polymerase chain reaction (PCR) analysis of the mRNA levels of Pygo2 in 50 paired HCC cancer/adjacent non-cancerous tissues showed that Pygo2 mRNA expression was significantly higher in cancerous tissues (P = 0.009). Immunohistochemical analysis showed that abnormal Pygo2 protein expression in HCC patients was associated with age (P = 0.025), tumour size (P = 0.005), intra- or extra-hepatic metastasis (P = 0.029), vascular invasion (P = 0.026) and tumour differentiation (P = 0.004). Patients with normal Pygo2 protein expression showed a longer survival time (P = 0.031) and a higher 1-year survival rate (P = 0.032) than those with abnormal Pygo2 expression. Cox's proportional hazard regression model showed that abnormal Pygo2 protein expression was a risk factor associated with the prognosis of HCC patients (P = 0.043). CONCLUSION: To the best of our knowledge, this is the first report investigating Pygo2 expression patterns and their clinicopathological significance in HCC. Our findings suggest that Pygo2 may be an important predictor of poor outcome in HCC patients, and could serve as a novel biomarker for HCC.

Distribution and Clinicopathological Features of Mott Cells (Plasma Cells Containing Russell Bodies) in Gastric Cancer: Presence of Mott Cells Is Associated with Favorable Prognosis.

Gastric cancer (GC) is still one of the leading causes of cancer-related mortality. We previously reported the relationship between histological heterogeneity of tumor cells and molecular features in GC. The tumor microenvironment also has a crucial role in GC progression and therapeutic resistance. In this study, we focused on the tumor microenvironment, especially inflammatory cells in GC. Using GC tissue slides, we investigated the distribution and clinicopathological significance of inflammatory cell counts including eosinophils, neutrophils, lymphocytes, and plasma cells. Additionally, we investigated the relationship between Mott cells (plasma cells containing Russell bodies) and clinicopathological features. In neoplastic gastric mucosa, a high number of plasma cells was associated with low T-grade, early stage, and good prognosis. We then focused on Mott cells and found that their presence in neoplastic gastric mucosa was associated with lower T and N grades, early stage, and Helicobacter pylori infection and was inversely associated with CD44 and EGFR expression. Additionally, the presence of Mott cells was associated with good prognosis in advanced GC and was an independent favorable prognostic predictor. The presence of Mott cells in GC might be one useful prognostic predictor, and Mott cells might have an important role in the carcinogenesis of H. pylori infection.

Clinicopathological significance of androgen receptor expression in extramammary Paget disease: An analysis of 92 patients.

Extramammary Paget disease (EMPD) is a rare cutaneous malignant neoplasm arising in apocrine gland-rich areas. Although - like normal apocrine glands - EMPD frequently expresses androgen receptor (AR), the clinical significance of AR expression remains unclear. The present study investigated the clinicopathological impact of AR expression in EMPD. Immunohistochemistry for AR was performed in a retrospective cohort of 92 EMPD patients with 108 EMPD lesions, including 102 primary lesions, five lymph node [LN] metastases and one local recurrence. The total AR staining score was calculated as staining intensity score (IS 0-3) × positive-cell percentage score (PS 1-4). Expression levels were graded as Grade 1 (scores 0 and 1), Grade 2 (scores 2-4), and Grade 3 (scores 6-12). Higher expression grade was correlated with tumor thickness (P = 0.011), LN metastasis (P = 0.008), and higher EMPD stage (P = 0.023). Grade 1 EMPDs did not invade into the dermis and did not generate metastatic and/or recurrent lesions, whereas only Grade 2 or 3 EMPDs did so. AR expression in invasive components was significantly higher (P = 0.023) than in non-invasive components remaining within the epidermis. AR expression was further elevated in metastatic and/or recurrent lesions relative to locally invasive lesions (P = 0.014). These results clearly indicate that increased AR expression is associated with malignant progression of EMPD and that androgen blockade might be an effective therapy. Furthermore, AR expression assessed by immunohistochemistry may have potential for prediction of LN metastasis and local recurrence in EMPD.

MCM4 expression is associated with high-grade histology, tumor progression and poor prognosis in urothelial carcinoma.

BACKGROUND: We previously reported Minichromosome maintenance 4 (MCM4) overexpression in gastric cancer. However, the clinicopathological significance of MCM4 in urothelial carcinoma (UC) has not been investigated. To clarify the clinicopathological significance of MCM4 in UC, we investigated MCM4 expression with immunohistochemistry (IHC). METHODS: We analyzed the expression and distribution of MCM4 in 124 upper tract urothelial carcinoma (UTUC) samples by IHC. Additionally, using 108 urine samples, we analyzed MCM4 Immunocytochemistry (ICC) expression in urine cytology. RESULTS: In normal urothelium, MCM4 expression was weak or absent. Meanwhile, the strong nuclear expression of MCM4 was observed in UTUC tissues, and it was detected in 77 (62%) of a total of 124 UTUC cases. MCM4-positive UTUC cases were associated with nodular/flat morphology, high grade, high T stage, and poor prognosis. Moreover, MCM4 expression was significantly higher in the invasive front than in the tumor surface. Similar results were also obtained in TCGA bladder cancer cohort. Additionally, MCM4 expression was associated with high expression of Ki-67, HER2, EGFR, and p53 in UTUC. Among representative cancer-related molecules, MCM4 had an independent predictive value for progression-free survival and high-grade UC. ICC for MCM4 was also performed on urine cytology slides and showed that the nuclear expression of MCM4 was more frequently found in UC cells than in non-neoplastic cells. The diagnostic accuracy of urine cytology was improved by combining MCM4 immunostaining with cytology. CONCLUSION: These results suggest that MCM4 might be a useful predictive biomarker for high-grade histology, tumor progression and poor prognosis in UC. Moreover, ICC for MCM4 might be helpful for UC detection as additional markers in the cytomorphology-based diagnosis.

Clinicopathological value of hematopoietic cell kinase overexpression in laryngeal squamous cell carcinoma tissues.

Laryngeal squamous cell carcinoma (LSCC) is the most lethal cancer in head and neck tumors. Although hematopoietic cell kinase (HCK) has been proven to be an oncogene in several solid tumors, its roles in LSCC remain obscure. This is the first study to evaluate the clinical value of HCK in LSCC, with the aim of exploring its expression status and potential molecular mechanisms underlying LSCC. LSCC tissue-derived gene chips and RNA-seq data were collected for a quantitive integration of HCK mRNA expression level. To confirm the protein expression level of HCK, a total of 82 LSCC tissue specimens and 56 non-tumor laryngeal epithelial controls were collected for in-house tissue microarrays and immunohistochemical staining. Kaplan-Meier curves were generated to determine the ability of HCK in predicting overall survival, progress-free survival, and disease-free survival of LSCC patients. LSCC overexpressed genes and HCK co-expressed genes were intersected to preliminarily explore the enriched signaling pathways of HCK. It was noticed that HCK mRNA was markedly overexpressed in 323 LSCC tissues compared with 196 non-LSCC controls (standardized mean difference = 0.81, p < 0.0001). Upregulated HCK mRNA displayed a moderate discriminatory ability between LSCC tissues and non-tumor laryngeal epithelial controls (area under the curve = 0.78, sensitivity = 0.76, specificity = 0.68). The higher expression level of HCK mRNA could predict worse overall survival and disease-free survival for LSCC patients (p = 0.041 and p = 0.013). Lastly, upregulated co-expression genes of HCK were significantly enriched in leukocyte cell-cell adhesion, secretory granule membrane, and extracellular matrix structural constituent. Immune-related pathways were the predominantly activated signals, such as cytokine-cytokine receptor interaction, Th17 cell differentiation, and Toll-like receptor signaling pathway. In conclusion, HCK was upregulated in LSCC tissues and could be utilized as a risk predictor. HCK may promote the development of LSCC by disturbing immune signaling pathways.

Clinicopathological and prognostic significance of heat shock proteins in hepatocellular carcinoma: a systematic review and meta-analysis.

Background: Overexpression of heat shock proteins (HSPs) has been observed in a wide range of human tumors, and there is an increasing evidence demonstrated that HSPs play a key role in tumor progression. Several studies were conducted to explore the clinicopathological characteristics and prognostic value of HSPs in hepatocellular carcinoma (HCC), but the results remain controversial. To address this gap, we conducted a systematic review and meta-analysis. Methods: The eligible literature was obtained from PubMed, Cochrane library, Web of science, Embase, Chinese National Knowledge Infrastructure and Wan Fang databases. We used the odds ratio (OR) and hazard ratio (HR) as the suitable parameters to assess the clinicopathological features and prognostic value of HSPs in HCC patients. Results: The meta-analysis results showed that HSPs expression was associated with overall survival (OS) of HCC patients (HR = 1.61, 95%CI = 1.22-2.13, P=0.001, I 2 = 62.7%). In addition, the pooled results suggested that HSPs expression was significantly correlated with tumor differentiation (OR = 1.33, 95%CI = 1.08-1.65, P = 0.907), vascular invasion (OR = 1.31, 95%CI = 1.02-1.69, P = 0.921) and lymphatic metastasis (OR=1.98, 95%CI= 1.70-2.31, P = 0.740). Meanwhile, the subgroup analysis showed a significant correlation between the expression of HSP27 (HR=1.69, 95%CI = 1.24-2.31, P = 0.674) and HSP90α (HR=2.03, 95%CI = 1.73-2.40, P = 0.743) with OS of HCC patients. Conclusions: Our meta-analysis confirms that HSPs expression is closely associated with a worse prognosis in HCC patients, and may be directly involved in tumor differentiation and distant metastasis. In addition, the subgroup analysis results demonstrate that the expression of HSP27 and HSP90α can be served as potential prognostic predictors of HCC.

Triosephosphate isomerase 1 may be a risk predictor in laryngeal squamous cell carcinoma: a multi-centered study integrating bulk RNA, single-cell RNA, and protein immunohistochemistry.

BACKGROUND: Although great progress has been made in anti-cancer therapy, the prognosis of laryngeal squamous cell carcinoma (LSCC) patients remains unsatisfied. Quantities of studies demonstrate that glycolytic reprograming is essential for the progression of cancers, where triosephosphate isomerase 1 (TPI1) serves as a catalytic enzyme. However, the clinicopathological significance and potential biological functions of TPI1 underlying LSCC remains obscure. METHODS: We collected in-house 82 LSCC tissue specimens and 56 non-tumor tissue specimens. Tissue microarrays (TMA) and immunohistochemical (IHC) experiments were performed. External LSCC microarrays and bulk RNA sequencing data were integrated to evaluate the expression of TPI1. We used a log-rank test and the CIBERSORT algorithm to assess the prognostic value of TPI1 and its association with the LSCC microenvironment. Malignant laryngeal epithelial cells and immune-stromal cells were identified using inferCNV and CellTypist. We conducted a comprehensive analysis to elucidate the molecular functions of TPI1 in LSCC tissue and single cells using Pearson correlation analysis, high dimensional weighted gene co-expression analysis, gene set enrichment analysis, and clustered regularly interspaced short palindromic repeats (CRISPR) screen. We explored intercellular communication patterns between LSCC single cells and immune-stromal cells and predicted several therapeutic agents targeting TPI1. RESULTS: Based on the in-house TMA and IHC analysis, TPI1 protein was found to have a strong positive expression in the nucleus of LSCC cells but only weakly positive activity in the cytoplasm of normal laryngeal cells (p < 0.0001). Further confirmation of elevated TPI1 mRNA expression was obtained from external datasets, comparing 251 LSCC tissue samples to 136 non-LSCC tissue samples (standardized mean difference = 1.06). The upregulated TPI1 mRNA demonstrated a high discriminative ability between LSCC and non-LSCC tissue (area under the curve = 0.91; sensitivity = 0.87; specificity = 0.79), suggesting its potential as a predictive marker for poor prognosis (p = 0.037). Lower infiltration abundance was found for plasma cells, naïve B cells, monocytes, and neutrophils in TPI-high expression LSCC tissue. Glycolysis and cell cycle were significantly enriched pathways for both LSCC tissue and single cells, where heat shock protein family B member 1, TPI1, and enolase 1 occupied a central position. Four outgoing communication patterns and two incoming communication patterns were identified from the intercellular communication networks. TPI1 was predicted as an oncogene in LSCC, with CRISPR scores less than -1 across 71.43% of the LSCC cell lines. TPI1 was positively correlated with the half maximal inhibitory concentration of gemcitabine and cladribine. CONCLUSIONS: TPI1 is dramatically overexpressed in LSCC than in normal tissue, and the high expression of TPI1 may promote LSCC deterioration through its metabolic and non-metabolic functions. This study contributes to advancing our knowledge of LSCC pathogenesis and may have implications for the development of targeted therapies in the future.

The expression of Aquaporin-1 and Aquaporin-3 in extrahepatic cholangiocarcinoma and their clinicopathological significance.

BACKGROUND: The aim of the study was to evaluate the expression and clinicopathological significance of Aquaporin-1 (AQP1) and Aquaporin-3 (AQP3) in extrahepatic cholangiocarcinoma (EHCC). METHODS: Immunostaining of AQP1 and AQP3 was performed by EnVision immunohistochemistry in benign and malignant biliary tract tissues. RESULTS: The expression of AQP1 and AQP3 protein were significantly higher in EHCC tumor tissues (P < 0.05 or P < 0.01). Adenoma and paracancerous tissues with positive AQP1 and/or AQP3 protein expression exhibited atypical hyperplasia. AQP1 expression was positive correlated with AQP3 expression in EHCC (P < 0.01). TNM I + II stage and radical surgery, the positive expression of AQP1 and AQP3 In patients with well-differentiation, no invasion, no lymph metastasis, is lower (P < 0.05 or P < 0.01). Average overall survival time of those with positive expression of AQP1 and AQP3 was significant shorter (P < 0.01). Both AQP1 and AQP3 positive expressions were proved to be an independent prognostic factors in EHCC by cox multivariate analysis. The AUC calculated for AQP1 was 0.769 (95% confidence interval [CI]: 0.618-0.920), and that for AQP3 was 0.758 (95%CI: 0.605-0.911, while that for AQP1 and AQP3 was 0.825 (95%CI: 0.658-0.991). CONCLUSIONS: Positive expression of AQP1 and AQP3 is closely related to the pathogenesis, severe clinicopathological characteristics, aggressive biological behaviors, and dismal prognoses in EHCC.

Clinicopathological significance of claspin overexpression and its efficacy as a novel biomarker for the diagnosis of urothelial carcinoma.

We previously reported that claspin is a key regulator in the progression of gastric cancer and renal cell carcinoma. However, the clinicopathological significance of claspin in urothelial carcinoma (UC) has not been investigated. We analyzed the expression and distribution of claspin in UC cases by immunohistochemistry. In the non-neoplastic urothelium, the expression of claspin was either weak or absent, whereas UC tissues showed nuclear staining. The expression of claspin was detected in 58 (42%) of a total of 138 upper tract UC cases treated by radical nephroureterectomy without neoadjuvant chemotherapy. Claspin-positive UC cases were associated with nodular/flat morphology, variant histology, high tumor grade, high pathological T grade, and lymphatic and venous invasion. The expression of claspin was significantly associated with decreased progression-free survival and cancer-specific survival. In addition, claspin was co-expressed with Ki-67, PD-L1, HER2, EGFR, and p53 in consecutive tumor sections of UC. An immunohistochemical analysis of claspin in biopsy specimens revealed that strong to moderate claspin staining was more frequently observed in carcinoma in situ in comparison to dysplasia or the benign urothelium. Furthermore, immunocytochemistry for claspin on urine cytology slides demonstrated that the proportion of claspin-positive cells was significantly greater in high-grade UC than in benign cases. These results suggest that claspin may be a novel prognostic marker and a possible therapeutic target molecule for UC. Moreover, claspin could be a useful diagnostic biomarker of urothelial neoplasia.

Overexpression of Mena is associated with tumor progression and poor prognosis in oral squamous cell carcinoma via EMT.

Background: Mena, a cytoskeletal regulatory protein, is involved in actin-based regulation of cell motility and adhesion, and contributes to tumor invasion and metastasis. However, the role of Mena in oral squamous cell carcinoma remains unclear. This is the first research focusing on the prognostic value of Mena in OSCC. In this study, we aimed to investigate the correlation between Mena expression and clinicopathological significance, as well as prognostic value in OSCC. Methods: Mena gene expression profiles of OSCC and normal tissues were collected from Oncomine, TCGA, and GEO databases. Biological function was analyzed through GO, KEGG and GSEA enrichment. Further, the expression level of Mena and tumor-related markers in 151 OSCC specimens was examined by IHC staining based on tissue microarray. Kaplan-Meier analysis was used to assess the prognostic performance of Mena in OSCC. Result: Mena was generally upregulation in various malignancies, especially OSCC. The functional analyses indicated that Mena was involved in the assembly and regulation of actin, cell movement, and EMT. IHC staining revealed that high expression of Mena in OSCC was correlated with Lymphatic metastasis, TNM stage, E-cadherin, Vimentin, and MMP-2, but insignificantly Ki67. Kaplan-Meier analysis demonstrated that elevated expression of Mena was significantly associated with poor overall survival and disease-free survival of OSCC patients. Conclusion: Mena could be a novel biomarker for predicting the prognosis of OSCC patients, which supports a theoretical basis for developing molecular target therapy.

Rac3 Expression and its Clinicopathological Significance in Patients With Bladder Cancer.

Background: Ras-related C3 botulinum toxin substrate 3 (Rac3) is overexpressed in malignancies and promotes tumor progression. However, the correlations between Rac3 expression and the clinicopathological characteristics and prognoses of patients with bladder cancer (BC) remain unclear. Methods: Data from The Cancer Genome Atlas (TCGA) were used to analyze Rac3 expression in BC and normal bladder tissues and validated using the Oncomine database, quantitative real-time PCR (qRT-PCR) and western blot. The Kaplan-Meier method was used to analyze the relationship between Rac3 expression and the prognosis of patients with BC. Cox univariate and multivariate analyses of BC patients overall survival (OS) were performed. Signaling pathways that potentially mediate Rac3 activity in BC were then analyzed by gene set enrichment analysis (GSEA). Results: The Rac3 expression in BC tissues was significantly higher than that in normal bladder tissues. Rac3 expression was significantly correlated with grade and stage. Overexpression of Rac3 was associated with a poor prognosis. GSEA showed that the cell cycle, DNA replication, p53 signaling pathway and mismatch repair were differentially enriched in the high Rac3 expression phenotype. The qRT-PCR and western blot results confirmed that the Rac3 expression in BC tissues was higher than that in normal bladder tissues. Conclusion: Rac3 is highly expressed in BC, which is related to the advanced clinicopathological variables and adverse prognosis of patients with BC. These results provide a new therapeutic target for BC.