Chen-Yue Qian

The Association of Transporter Genes Polymorphisms and Lung Cancer Chemotherapy Response

Lung cancer is one of the most common cancers and is the leading cause of death worldwide. Platinum-based chemotherapy is the main treatment method in lung cancer patients. Our previous studies indicated that single nucleotide polymorphisms (SNPs) in some transporter genes played important role in platinum-based chemotherapy efficacy. The aim of this study was to investigate the association of SNPs in transporter genes and platinum-based chemotherapy efficacy. The main polymorphisms on transporters OCT2, LRP, AQP2, AQP9 and TMEM205 genes were genotyped in 338 lung cancer patients. The rs195854 in genotypic model, rs896412 in genotypic and recessive models for all subjects showed significant association with chemotherapy response. In stratification analysis, TMEM205 rs896412, OCT2 rs1869641 and rs195854, AQP9 rs1516400 and AQP2 rs7314734 showed significant relation to chemotherapy response. In conclusion, the genetic polymorphisms in OCT2, AQP2, AQP9 and TMEM205 may contribute to chemotherapy response in lung cancer patients.

Association of HMGB1 and HMGB2 genetic polymorphisms with lung cancer chemotherapy response.

The aim of the present study was to investigate the association of genetic polymorphisms in high mobility group box 1 and 2 (HMGB1 and HMGB2, respectively) with platinum‐based chemotherapy responses in Chinese lung cancer patients. In total, 338 Chinese lung cancer patients (154 responders and 184 non‐responders) were recruited to the study. All patients received at least two cycles of first‐line platinum‐based chemotherapy. Three tagging single nucleotide polymorphisms (SNPs) of HMGB1 and two tagging SNPs of HMGB2 were detected in patients. We found that rs1412125 and rs2249825 of HMGB1 were significantly associated with the platinum‐based chemotherapy response in both recessive and genotypic models. In addition, rs1412125 showed significant association with platinum‐based chemotherapy response for the subgroup of patients aged >55 years in additive, recessive and genotypic models. No significant associations were detected between other SNPs and the platinum‐based chemotherapy response. The HMGB1 SNPs (rs1412125 and rs2249825) were associated with platinum‐based chemotherapy responses in Chinese lung cancer patients. In conclusion, HMGB1 SNPs may serve as potential biomarkers for predicting the efficacy of platinum‐based chemotherapy.

WISP1 Polymorphisms Contribute to Platinum-Based Chemotherapy Toxicity in Lung Cancer Patients

Platinum-based chemotherapy toxicity is always one of the serious problems from which lung cancer patients suffer. The genetic polymorphism of WISP1 was revealed to be associated with susceptibility and platinum-based chemotherapy response in our previous studies. In this study, we aimed to investigate the relationship of WISP1 genetic polymorphisms with platinum-based chemotherapy toxicity in lung cancer patients. A total of 412 lung cancer patients were enrolled in this study, and 28 polymorphisms of the WISP1 gene were genotyped by SequenomMassARRAY. We found that WISP1 polymorphisms (rs2929965, rs2929969, rs2929970, rs2929973 and rs754958) were related to the overall chemotherapy toxicity of lung cancer in subgroup analyses. Rs16904853, rs2929970, rs2977549 and rs2977551 (p = 0.021, 0.028, 0.024, 0.048, respectively) polymorphisms were significantly associated with hematologic toxicity. Rs2929946, rs2929970, rs2977519, rs2977536, rs3739262 and rs754958 (p = 0.031, 0.046, 0.029, 0.016, 0.042, 0.035, respectively) polymorphisms were significantly associated with the gastrointestinal toxicity of lung cancer. Genotypes of WISP1 may be novel and useful biomarkers for predicting platinum-based chemotherapy toxicity in lung cancer patients.

Association of positively selected eIF3a polymorphisms with toxicity of platinum-based chemotherapy in NSCLC patients.

Aim:Eukaryotic translation initiation factor 3 subunit A (eIF3a) plays critical roles in regulating the initiation of protein translation, and eIF3a is highly expressed in lung cancer. In this study, we investigated the association of the positively selected SNPs of eIF3a with the response to and toxicity of platinum-based chemotherapy in Chinese patients with non-small cell lung cancer (NSCLC).Methods:SNP data for eIF3a locus were downloaded from HapMap database. For each SNP, haplotype, LD profile and population differentiation were analyzed. The long-range haplotype (LRH) test was employed to identify positively selected SNPs of eIF3a. A total of 325 NSCLC patients were enrolled and genotyped for these SNPs.Results:Five positively selected (rs1409314, rs4752219, rs4752220, rs7091672 and rs10510050) and 5 non-positively selected SNPs (rs10886342, rs11198804, rs2275112, rs10787899 and rs4752269) were identified in the LRH test. However, none of them was correlated with the platinum-based chemotherapy response. In contrast, 4 of the positively selected SNPs (rs1409314, rs4752219, rs4752220 and rs7091672) were significantly correlated with the toxicities tested (neutropenia, anemia, thrombocytopenia, emesis and hepatotoxicity). In addition, rs10510050 was significantly correlated with thrombocytopenia, emesis and hepatotoxicity. None of the 5 non-positively selected SNPs was correlated with the 5 toxicities.Conclusion:The positively selected SNPs of eIF3a are significantly correlated with platinum-based chemotherapy toxicities in Chinese NSCLC patients.

Association of Wnt-Inducible Signaling Pathway Protein 1 Genetic Polymorphisms With Lung Cancer Susceptibility and Platinum-Based Chemotherapy Response

BACKGROUND Platinum-based chemotherapy is the main treatment method for lung cancer patients. The genetic polymorphisms of Wnt-inducible signaling pathway protein 1 (WISP1) were reported to be associated with the development of diverse lung diseases. In this study, we aimed to investigate the relationship of WISP1 genetic polymorphisms with lung cancer susceptibility and platinum-based chemotherapy response in Chinese lung cancer patients. MATERIALS AND METHODS A total of 556 lung cancer patients and 254 healthy controls were enrolled onto this study. The 28 polymorphisms of the WISP1 gene were genotyped by the Sequenom MassARRAY system. RESULTS We found that WISP1 rs16893344, rs2977530, rs2977537, and rs62514004 (P = .009, .033, .049, and .036, respectively) polymorphisms were related to susceptibility of lung cancer; and WISP1 rs11778573 (P = .023, nonsmokers), rs16893344 (P = .013, ≥ 50 years old), rs2977536 (P = .039, ≥ 50 years old; P = .044, nonsmokers; P = .047, non-small-cell lung cancer, respectively), rs2977549 (P = .013, smokers), and rs62514004 (P = .033, ≥ 50 years old) polymorphisms were significantly associated with platinum-based chemotherapy response in lung cancer patients. CONCLUSION Genotypes of WISP1 may be novel and useful biomarkers for diagnosis of lung cancer and evaluation of platinum-based chemotherapy response in lung cancer patients.

Effect of transporter and DNA repair gene polymorphisms to lung cancer chemotherapy toxicity

Lung cancer is the first leading cause of cancer deaths. Chemotherapy toxicity is one of factors that limited the efficacy of platinum-based chemotherapy in lung cancer patients. Transporters and DNA repair genes play critical roles in occurrence of platinum-based chemotherapy toxicity. To investigate the relationships between transporter and DNA repair gene polymorphisms and platinum-based chemotherapy toxicity in lung cancer patients, we selected 60 polymorphisms in 14 transporters and DNA repair genes. The polymorphisms were genotyped in 317 lung cancer patients by Sequenom MassARRAY. Logistic regression was performed to estimate the association of toxicity outcome with the polymorphisms by PLINK. Our results showed that polymorphisms of SLC2A1 (rs3738514, rs4658, rs841844) were significantly related to overall toxicity. XRCC5 (rs1051685, rs6941) and AQP2 (10875989, rs3759125) polymorphisms were associated with hematologic toxicity. AQP2 polymorphisms (rs461872, rs7305534) were correlated with gastrointestinal toxicity. In conclusion, genotypes of these genes may be used to predict the platinum-based chemotherapy toxicity in lung cancer patients.

Genome-scale long noncoding RNA expression pattern in squamous cell lung cancer

In this study, we aimed to explore the long noncoding RNA expression pattern in squamous cell lung cancer (SQCC) on a genome-wide scale. Total RNAs were extracted from 16 lung SQCC patients’ normal and matched lung cancer tissues by Trizol reagent. The expression level of genome-wide scale lncRNA and mRNA was determined by microarray. qRT-PCR was used to validate the lncRNA expression level in 47 patients. Data analyses were performed using R and Bioconductor. A total of 2,748 up and 852 down regulated probes were identified to be significantly and differentially expressed in tumor tissues. The annotation result of their co-expressed mRNAs showed that the most significantly related category of GO analysis was development and differentiation, while the most significantly related pathway was cell cycle. Subgroup analysis identified that 46 and 18 probes were specifically differentially expressed in smoking and moderately differentiated tumors, respectively. Our study indicated that clusters of lncRNAs were significantly and differentially expressed in SQCC compared with normal tissues in the same subject. They may exert a significant role in lung cancer development and could be potential targets for future treatment of SQCC.