BackgroundThe clinicopathologic characteristics of tumors expressing programmed death (PD-1) ligands (PD-Ls) PD-L1 or PD-L2 and their associations with common driver mutations in lung adenocarcinoma are not clearly defined, despite the progression of anti-PD-1/PD-L1 immunotherapy.MethodsPD-L1 and PD-L2 expression was measured by immunohistochemistry in 143 surgically resected lung adenocarcinomas and was correlated with clinical variables, histologic subtypes, and the mutational status of EGFR, KRAS, HER2, and ALK.ResultsPositive PD-L1 expression was significantly associated with more advanced T status, N status, and pathologic stage. Histologically, lung adenocarcinomas with positive PD-L1 staining were less likely to be adenocarcinoma in situ or minimally invasive adenocarcinoma and more likely to have solid predominant subtype. Both PD-L1 expression (odds ratio =1.984, 95% confidence interval =1.010–3.894; P=0.047) and PD-L2 expression (odds ratio =2.328, 95% confidence interval =1.201–4.512; P=0.012) were independent predictors of poor overall survival. When the combined PD-L expression and pathologic stage were used together to predict overall survival, the concordance index increased to 0.763, and the Akaike information criteria value decreased to 356.08.ConclusionWe defined the clinicopathologic features of lung adenocarcinomas with high expression of PD-L1 and PD-L2. We further demonstrated the role of PD-L expression as a useful prognostic marker for lung adenocarcinoma.

BackgroundLung adenocarcinoma with micropapillary and solid predominant subtypes was reported to be associated with poor prognosis; however, whether minor components (non-predominant) of micropapillary and solid subtypes predict poor prognosis remains unknown. In this study, we investigated the predictive and prognostic value of lymph node metastasis of minor micropapillary and solid components.MethodsSpecimens of resected tumors of 1244 patients were reclassified to determine the predominant subtype and minor components (>5 %, but not predominant). Of these specimens, 105 contained a micropapillary component and 210 contained a solid component. The correlation between each subtype and lymph node metastasis was analyzed, and survival analyses were used to determine the association between each subtype and patient survival.ResultsAdenocarcinomas harboring micropapillary and/or solid components held higher rates of metastatic lymph node stations (25.2 % vs. 15.6 %, p = 0.002; and 24.0 % vs. 14.9 %, p < 0.001, respectively) and lymph nodes (17.3 % vs. 10.1 %, p = 0.004; and 15.5 % vs. 9.7 %, p = 0.001, respectively). Patients with micropapillary and solid components in their tumors showed a shorter median recurrence-free survival (15.8 vs. 62.8 months, p < 0.001; and 20.8 months vs. not reached, p < 0.001) and overall survival (47.0 months vs. not reached, p < 0.001; and 69.0 months vs. not reached, p < 0.001).ConclusionsMinor components of micropapillary and/or solid subtypes of lung adenocarcinoma are correlated with lymph node metastasis and poor prognosis. Thus, it is beneficial to focus not only on predominant subtypes but also minor components to predict prognoses and make therapeutic strategies more comprehensively.Electronic supplementary materialThe online version of this article (doi:10.1245/s10434-015-5043-9) contains supplementary material, which is available to authorized users.

An A to G transition at the 181 base pair position upstream of the transcription initiation site of the matrix metalloproteinase-7 (MMP-7) gene (-181A/G) may modify the development and progression of some diseases via influencing the transcription activity of the promoter. To assess the effects of the functional single nucleotide polymorphism on cancer susceptibility and progression, the MMP-7 -181A/G genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis among 258 patients with esophageal squamous cell carcinoma (ESCC), 201 patients with gastric cardiac carcinoma (GCA), 243 patients with non-small cell lung carcinoma (NSCLC) and 350 healthy individuals without cancer. The result showed that the frequency of the -181G allele in ESCC, GCA and NSCLC patients was significantly higher than that in healthy controls (P = 0.019, 0.023 and 0.004, respectively). Compared with the A/A genotype, genotypes with the -181G allele (A/G + G/G) significantly increased susceptibility to all three tumors, with adjusted odds ratio of 1.83 (95% CI = 1.12-2.99) for ESCC, 1.96 (95% CI = 1.17-3.29) for GCA and 2.00 (95% CI = 1.23-3.24) for NSCLC. Stratification analysis showed that smoking did not significantly influence the association between the MMP-7-181A/G and GCA or NSCLC, while the -181G allele only significantly increased susceptibility to ESCC among smokers. In addition, association between the -181G allele and susceptibility to ESCC and GCA showed significance only among individuals with family history of upper gastrointestinal cancer. The correlation of the MMP-7-181A/G polymorphism with potential of lymphatic metastasis was not observed in all three tumors. The study suggested that, the MMP-7-181A/G polymorphism might be a candidate marker for predicting individuals who are at higher risk to certain tumors but might not be used to predict potential of lymphatic metastasis in ESCC, GCA and NSCLC.

The physiological and pathological roles of hydrogen sulfide (H2S) in the regulation of cardiovascular functions have been recognized. Cystathionine gamma-lyase (CSE) is a major H2S-producing enzyme in cardiovascular system. Ischemic post-conditioning (PC) provides cadioprotection in young hearts but lost in the aging hearts. The involvement of H2S in the recovery of PC-induced cardioprotection in the aging hearts is unclear. In the present study, we demonstrated that ischemia/reperfusion (I/R) decreased H2S production rate and CSE expression, aggravated cardiomyocytes damage, apoptosis and myocardial infarct size, reduced cardiac function, increased the levels of Bcl-2, caspase-3 and caspase-9 mRNA, enhanced oxidative stress in isolated young and aging rat hearts. I/R also increased the release of cytochrome c and down-regulated the phosphorylation of PI3K, Akt and GSK-3β in the aging rat hearts. We further found that PC increased H2S production rate and CSE expressions, and protected young hearts from I/R-induced cardiomyocytes damage, all of which were disappeared in the aging hearts. Supply of NaHS not only increased PC-induced cardioprotection in the young hearts, but also lightened I/R induced-myocardial damage and significantly recovered the cardioprotective role of PC against I/R induced myocardial damage in the aging hearts. LY294002 (a PI3K inhibitor) abolished but N-acetyl-cysteine (NAC, an inhibitor of reactive oxygen species, ROS) further enhanced the protective role of H2S against I/R induced myocardial damage in the aging hearts. In conclusion, these results demonstrate that exogenous H2S recovers PC-induced cardioprotection via inhibition of oxidative stress and up-regulation of PI3K-Akt-GSK-3β pathway in the aging rat hearts. These findings suggested that H2S might be a novel target for the treatment of aging cardiovascular diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s13578-015-0003-4) contains supplementary material, which is available to authorized users.

The incidence of colorectal cancer (CRC) in young adults is rising. We aimed to analyze the clinicopathological characteristics and survival outcomes of young versus elderly CRC patients. All patients diagnosed with CRC in the Surveillance, Epidemiology, and End Results program data (1988–2011) from the United States were evaluated. They were divided into 3 groups by age at diagnosis: group 1 (20–40 years old), group 2 (41–50 years old), and group 3 (>50 years old). The clinicopathological characteristics and CRC-specific survival (CRC-SS) were evaluated and compared among the 3 groups. A total of 279,623 CRC patients were included: 6700 (2.4%) in group 1, 19,385 (6.9%) in group 2, and 253,538 (90.7%) in group 3. Young CRC patients had more tumors located in rectum, fewer cases with multiple tumors, later stage, more mucinous carcinoma and signet ring-cell carcinoma, more poor differentiated tumors, and more lymph nodes (no. ≥12) examined. The 5-year CRC-SS rates of patients in groups 1, 2, and 3 were 65.1%, 67.1%, and 62.8%, respectively (group 1 vs group 2, P = 0.001; group 1 vs group 3, P < 0.001; group 2 vs group 3, P < 0.001). Multivariate analysis revealed older (>50 years old) age was an independent predictor of poor prognosis (hazard ratio, 1.545; 95% confidence interval, 1.456–1.639; P < 0.001). Young CRC patients had later stage presentation and more aggressive pathological features, but better survival. CRC patients aged 41 to 50 years had best CRC-SS in contrast to patients in another 2 age groups.