Jinghe Li

PKM2 and ACVR 1C are prognostic markers for poor prognosis of gallbladder cancer

PurposeTo identify biological markers related to the progression and prognosis of GBC.MethodsThe expressions of pyruvate kinase isoenzyme type M2 (PKM2) and activin A receptor type IC (ACVR 1C) in 46 squamous cell/adenosquamous carcinomas (SC/ASC) and 80 adenocarcinomas (AC) were examined using immunohistochemistry.ResultsPositive PKM2 and negative ACVR 1C expressions were significantly associated with lymph node metastasis, invasion and TNM stage of SC/ASCs and ACs. Univariate Kaplan–Meier analysis showed that either elevated PKM2 or loss of ACVR 1C expression significantly correlated with shorter average survival times in both SC/ASC and AC patients. Multivariate Cox regression analysis showed that positive PKM2 expression and loss of ACVR 1C expression were poor prognosis biomarkers in both SC/ASC and AC patients.ConclusionsOur study suggested that PKM2 overexpression is a marker of metastasis, invasion and poor prognosis of GBC. ACVR 1C is a tumor suppressor, and lowered ACVR 1C expression is an important marker for the metastasis, invasion, and prognosis of GBC.

Positive ALDH1A3 and Negative GPX3 Expressions Are Biomarkers for Poor Prognosis of Gallbladder Cancer

Background. Gallbladder cancers (GBCs) are highly aggressive cancers with high mortality. However, biological markers for the progression and prognosis of GBC are currently unavailable in the clinic. Objective. To identify biomarkers for predicting GBC metastasis and prognosis. Methods. We examined ALDH1A3 and GPX3 expressions in 46 squamous cell/adenosquamous carcinomas (SC/ASC) and 80 adenocarcinomas (AC) by using immunohistochemistry. Results. Positive ALDH1A3 and negative GPX3 expressions were significantly associated with lymph node metastasis and invasion of SC/ASCs and ACs. Univariate Kaplan-Meier analysis showed that either positive ALDH1A3 (P < 0.001) or negative GPX3 (P < 0.001) expression significantly correlated with decreased overall survival in both SC/ASC and AC patients. Multivariate Cox regression analysis showed that positive ALDH1A3 expression or negative GPX3 expression was an independent poor-prognostic predictor in both SC/ASC and AC patients. Conclusions. Our study suggested that positive ALDH1A3 and negative GPX3 expressions are closely associated with clinical pathological behaviors and poor prognosis of gallbladder cancer.

CFL1 and Arp3 are Biomarkers for Metastasis and Poor Prognosis of Squamous Cell/Adenosquamous Carcinomas and Adenocarcinomas of Gallbladder

Cofilin-1 (CFL1) and Arp3 expression in 46 squamous cell and adenosquamous carcinomas (SC/ASCs) and 80 adenocarcinomas (ACs) were measured by using immunohistochemistry. Positive CFL1 and Arp3 expression were significantly associated with large tumor size, high TNM stage, lymph node metastasis, and decreased overall survival in both SC/ASC and AC patients (p < .001). Multivariate Cox regression analysis showed that positive CFL1 and Arp3 expression are independent poor-prognostic factors for both SC/ASC and AC patients. Our study suggested that positive CFL1 and Arp3 expression are closely related to tumor progression, metastasis, and poor prognosis of gallbladder cancer.

ILK and PRDX1 are prognostic markers in squamous cell/adenosquamous carcinomas and adenocarcinoma of gallbladder

Although the incidence of gallbladder cancers is low, they are highly aggressive tumors. Squamous cell/adenosquamous carcinoma (SC/ASC) is a rare subtype of gallbladder cancer. The clinical characteristics of SC/ASC have not been well documented, and no prognosis marker has been identified. In this study, we examined integrin-linked kinase (ILK) and peroxiredoxin-1 (PRDX1) expression in 46 SC/ASCs and 80 adenocarcinomas (ACs) by using immunohistochemistry and analyzed their correlations with clinicopathological characteristics. We demonstrated that positive ILK and PRDX1 expressions were significantly associated with large tumor size, high TNM stage, lymph node metastasis, and invasion of SC/ASC and AC. Univariate Kaplan–Meier analysis showed that positive ILK and PRDX1 expressions were closely associated with decreased overall survival in both SC/ASC (p < 0.001 and p = 0.005, respectively) and AC (p < 0.001) patients. Multivariate Cox regression analysis showed that positive ILK and PRDX1 expressions were an independent poor prognostic predictor in both SC/ASC and AC patients. We also revealed a similar significance of differentiation, tumor size, TNM stage, lymph node metastasis, invasion, and surgical curability with survival in SC/ASC and AC patients. Our study suggested that positive ILK and PRDX1 expressions are closely related to the progression and poor prognosis of gallbladder cancer.

N-cadherin and P-cadherin are biomarkers for invasion, metastasis, and poor prognosis of gallbladder carcinomas.

Gallbladder cancer (GBC) is a rare, but highly aggressive cancer. The most common type of gallbladder cancer is adenocarcinoma (AC), while squamous cell/adenosquamous carcinoma (SC/ASC) is a rare type of gallbladder cancer. The clinicopathologic and biological characteristics of SC/ASC have not been well documented. In this study, the protein expression of N-cadherin and P-cadherin in 46 SC/ASCs and 80 ACs was measured using immunohistochemistry. We demonstrated that positive N-cadherin and P-cadherin expression were significantly associated with large tumor size, invasion, and lymph node metastasis of both SC/ASC and AC. In contrast, positive N-cadherin and P-cadherin expression were significantly associated with differentiation and TNM stage in only AC. Univariate Kaplan-Meier analysis showed that positive N-cadherin and P-cadherin expression, differentiation, tumor size, TNM stage, invasion, lymph node metastasis, and surgical curability were significantly associated with overall survival in both SC/ASC and AC patients. Multivariate Cox regression analysis showed that positive N-cadherin and P-cadherin expression are independent poor-prognostic factors in both SC/ASC and AC patients. Our study suggested that positive N-cadherin and P-cadherin expression closely correlated with clinicopathological and biological behaviors, and poor-prognosis of gallbladder cancer.

Paxillin and carbonic anhydrase IX are prognostic markers in gallbladder squamous cell/adenosquamous carcinomas and adenocarcinomas

Squamous cell/adenosquamous carcinomas (SC/ASC) are rare subtypes of gallbladder cancers (GBCs). Clinical characteristics of SC/ASC have not been well documented, and no biological markers of GBC carcinogenesis, progression and prognosis are available.

SHP2 and UGP2 are Biomarkers for Progression and Poor Prognosis of Gallbladder Cancer.

ABSTRACT Biomarkers for the diagnosis, prognosis, and targeting therapy of gallbladder cancers are not clinically available. This study demonstrated that the percentage of cases with positive SHP2 and UGP2 expression significantly correlated with the percentage of cases with positive vimentin, β-catenin, MMP2, MMP9, and Ki-67 expression, large tumor size, high TNM stage, lymph node metastasis, and survival in patients with adenocarcinomas and squamous cell/adenosquamous carcinomas. Positive SHP2 and UGP2 expression are independent poor-prognostic factors in both types of tumors. Our study suggested that positive SHP2 and UGP2 expression correlated with clinicopathological and biological behaviors, and poor-prognosis of gallbladder cancer.

TSG101 and PEG10 are prognostic markers in squamous cell/adenosquamous carcinomas and adenocarcinoma of the gallbladder.

The clinicopathological characteristics of squamous cell/adenosquamous carcinoma (SC/ASC) are currently not well documented, and as the prevalence of SC/ASC is uncommon in gallbladder cancers, a prognostic marker has not yet been found. In the present study, the expression of tumor susceptibility gene (TSG) 101 and paternally expressed gene (PEG) 10 was assessed in 46 SC/ASCs and 80 adenocarcinomas (ACs) using immunohistochemistry, and the samples were further analyzed to examine correlations with the clinicopathological characteristics. It was demonstrated that positive TSG101 and PEG10 expression were significantly associated with large tumor size, high tumor-node-metastasis (TNM) stage, lymph node metastasis, invasion and no resection (only biopsy) of SC/ASC and AC. The univariate Kaplan-Meier analysis showed that positive TSG101 and PEG10 expression, and differentiation, tumor size, TNM stage, lymph node metastasis, invasion and surgical curability, is closely associated with a decreased overall survival in SC/ASC and AC patients (P<0.05 or P<0.001). The multivariate Cox regression analysis identified that positive TSG101 and PEG10 expression are independent factors for a poor-prognosis in SC/ASC and AC patients. The present study indicates that positive TSG101 and PEG10 expression are closely associated with the clinical, pathological and biological behaviors, and a poor prognosis in gallbladder cancer.

MCM2 and TIP30 are prognostic markers in squamous cell/adenosquamous carcinoma and adenocarcinoma of the gallbladder

The clinicopathological and biological characteristics of squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder remain to be fully elucidated, due to the fact that it is a rare gallbladder cancer subtype. In the current study, the expression of minichromosome maintenance complex component 2 (MCM2) and HIV-1 tat interactive protein 2 (TIP30) was measured in 46 cases of SC/ASC and 80 adenocarcinomas (AC) using immunohistochemistry. Positive MCM2 and negative TIP30 expression were significantly associated with large tumor size, high TNM stage, invasion, lymph node metastasis and lack of surgical curability in SC/ASC and AC. Positive MCM2 and negative TIP30 expression were significantly associated with poor differentiation in AC, whereas only MCM2 was correlated with differentiation in SC/ASC. Univariate Kaplan-Meier analysis demonstrated that positive MCM2 and negative TIP30 expression, the degree of differentiation, tumor size, TNM stage, invasion, lymph node metastasis and surgical curability were significantly associated with post-operative survival in patients with SC/ASC and AC. Multivariate Cox regression analysis demonstrated that positive MCM2 and negative TIP30 expression, the degree of differentiation, tumor size, TNM stage, invasion, lymph node metastasis and lack of surgical curability were also independent predictors of poor prognosis in patients with SC/ASC and AC. These data suggest that positive MCM2 and negative TIP30 expression are closely correlated with the clinical, pathological and biological parameters, in addition to poor prognosis in patients with gallbladder cancer.

EphB1 and Ephrin-B, New Potential Biomarkers for Squamous Cell/adenosquamous Carcinomas and Adenocarcinomas of the Gallbladder

Squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder are rare tumors and there are few clinical reports in the literature. Herein we report our clinical experience with 46 patients with SC/ASC and 80 with adenocarcinoma (AC). Expression of EphB1 and Ephrin-B in each tumor was determined using immunohistochemical methods for determination of correlations with prognosis. There was no difference in EphB1 and Ephrin-B expression between SC/ASC and AC tumors (P>0.05), but greater expression in those less than 3 cm in diameter, stage I or II (TNM stage), with no lymph node metastases, with no local invasion and treated with radical resection was apparent. Expression of EphB1 (P<0.05) and Ephrin-B (P<0.01) was higher in well differentiated than in poorly differentiated AC tumors. Kaplan-Meier survival analysis indicated that degree of differentiation, tumor diameter, lymph node metastases, local invasion, surgical approach and expression rate of EphB1 and Ephrin-B were closely related to the survival of SC/ASC (P<0.05) and AC patients (P<0.01). Patients with tumors that positive expressed EphB1 and Ephrin-B, whether it is SC/ASC (P SC/ASC =0.000) or AC (P AC =0.000 or P AC =0.002) had longer survival than those negative expression. Cox multivariate analysis indicated a negative correlation between expression of EphB1 or Ephrin-B and overall survival. Hence, EphB1 and Ephrin-B could be regarded as independent good prognostic factorsand important biological markers for SC/ASC and AC of gallbladder.