Purpose
Caspase recruitment domain containing protein 9 (CARD9) has been demonstrated to be a pro-tumor factor in various cancers. However, our previous study found a significant decrease of CARD9 in malignant pleural effusion compared with benign pleural effusion. So we investigated the role of CARD9 in non-small cell lung cancer (NSCLC) and its working mechanism.
Materials and Methods
Immunohistochemistry, western blot, and quantitative real-time polymerase chain reaction were used to detect the expression of CARD9 in specimens of NSCLC patients. The Cancer Genome Atlas (TCGA) databasewas also used to analyze the expression of CARD9 in NSCLC and its predicting value for prognosis. Immunofluorescence was used for CARD9 cellular location. Cell growth assay, clonal formation assay, wound healing assay, matrigel invasion assay, and flow cytometry were used to test cell proliferation, migration, invasion, apoptosis, and cycle progression of NSCLC cells with CARD9 knockdown or CARD9 overexpression. Co-immunoprecipitation was used to identify the interaction between CARD9 and B-cell lymphoma 10 (BCL10). SB203580 was used to inhibit p38 activation.
Results
CARD9 was decreased in NSCLC tissues compared with normal tissues; low CARD9 expression was associated with poor survival. CARD9 was expressed both in tumor cells and macrophages. Downregulation of CARD9 in NSCLC cells enhanced the abilities of proliferation, invasion and migration via activated MAPK/p38 signaling, while overexpression of CARD9 presented antitumor effects. BCL10 was identified to interact with CARD9.
Conclusion
We demonstrate that CARD9 is an independent prognostic factor in NSCLC patients and inhibits proliferation, migration, and invasion by suppressing MAPK/p38 pathway in NSCLC cells.
Citations
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Purpose
This retrospective study aimed to evaluate the distribution pattern and prognostic value of 21-gene recurrence score (RS) in Chinese patients with mucinous breast cancer (MC) and compared with infiltrating ductal carcinoma (IDC).
Materials and Methods
Patients diagnosed with MC or IDC from January 2010 to January 2017 were retrospectively recruited. Reverse transcriptase–polymerase chain reaction assay of 21 genes was conducted to calculate the RS. Univariate and multivariate analyses were performed to assess the association between RS and clinicopathological factors. Survival outcomes including disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test.
Results
The MC cohort included 128 patients and the IDC cohort included 707 patients. The proportions of patients with a low (RS < 18), intermediate (18-30), or high risk (RS > 30) were 32.0%, 48.4%, and 19.5% in MC cohort, and 26.9%, 46.8% and 26.3% in IDC cohort. The distribution of RS varied significantly according to different Ki-67 index and molecular subtype in both cohorts. Moreover, the receipt of chemotherapy was associated with RS in both cohorts. Among patients with MC, tumor stage was related to the DFS (p=0.040). No significant differences in DFS and OS were found among MC patients in different RS risk groups (OS, p=0.695; DFS, p=0.926).
Conclusion
RS was significantly related to Ki-67 index and molecular subtypes in MC patients, which is similar in IDC patients. However, RS was not able to predict DFS and OS in patients with MC.
Citations
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Purpose
Despite the rapid growing of cancer survivors, prior cancer history is a commonly adopted exclusion criterion. Whether prior cancer will impact the survival of patients with advanced breast cancer (ABC) remains uncertain.
Materials and Methods
Patients with ABC diagnosed between 2004 and 2010 were identified using Surveillance, Epidemiology, and End Results (SEER) database. Timing, stage, and type were used to characterize prior cancer. Multivariable analyses using propensity score–adjusted Cox regression and competing risk regression were conducted to evaluate the prognostic effect of prior cancer on overall survival (OS) and breast cancer-specific survival (BCSS).
Results
A total of 14,176 ABC patients were identified, of whom 10.5% carried a prior cancer history. The most common type of prior cancer was female genital cancer (32.4%); more than half (51.7%) were diagnosed at localized stage; most were diagnosed more than 5 years (42.9%) or less than 1 year (28.3%) prior to the index cancer. In multivariate analyses, patients with prior cancer presented a slightly worse OS (hazard ratio, 1.18; 95% confidence interval [CI], 1.07 to 1.30; p=0.001) but a better BCSS (subdistribution hazard ratio, 0.64; 95% CI, 0.56 to 0.74; p < 0.001). In subset analyses, no survival detriment was observed in patients with prior malignancy from head and neck or endocrine system, at in situ or localized stage, or diagnosed more than 4 years.
Conclusion
Prior cancer provides an inferior OS but a superior BCSS for patients with ABC. It does not affect the survival adversely in some subgroups and these patients should not be excluded from clinical trials.
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Purpose
The purpose of this study was to investigate the changes of tumor infiltrating lymphocytes (TILs) between core needle biopsy (CNB) and surgery removed sample (SRS) in early stage breast cancer patients and to identify the correlating factors and prognostic significance of TILs changes.
Materials and Methods
A retrospective study was carried out on 255 patients who received CNB and underwent surgical resection for invasive breast cancer. Stromal TILs levels of CNB and SRS were evaluated respectively. Tumors with ≥50% stromal TILs were defined as lymphocyte-predominant breast cancer (LPBC). Clinicopathological variables were analyzed to determine whether there were factors associated with TILs changes. Log-rank tests and Cox proportional hazards models were used to analyze the influences of TILs and TILs changes on survival.
Results
SRS-TILs (median, 10.0%) were significant higher than CNB-TILs (median, 5.0%; p<0.001). Younger age (<60 years, p=0.016) and long surgery time interval (STI, ≥4 days; p=0.003) were independent factors correlating with higher TILs changes. CNB-LPBC patients showed better breast cancer-free interval (BCFI, p=0.021) than CNB-non-LPBC (CNB-nLPBC) patients. Patients were categorized into four groups according to the LPBC change pattern from CNB to SRS: LPBC→LPBC, LPBC→nLPBC, nLPBC→LPBC, and nLPBC→nLPBC, with estimated 5-year BCFI 100%, 100%, 69.7%, and 86.0% (p=0.016). nLPBC→LPBC pattern was an independent prognostic factor of worse BCFI (hazard ratio, 2.19; 95% confidence interval, 1.06 to 4.53; p=0.035) compared with other patterns.
Conclusion
TILs were significantly higher in SRS than in CNB. Higher TILs changes were associated with younger age and long STI. Changing from nLPBC to LPBC after CNB indicated a worse BCFI, which needs further validation.
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