ALOX5AP suppresses osteosarcoma progression via Wnt/ß-catenin/EMT pathway and associates with clinical prognosis and immune infiltration.

Osteosarcoma (OS) is one of the most common malignant neoplasms in children and adolescents. Immune infiltration into the microenvironment of the tumor has a positive correlation with overall survival in patients with OS. The purpose of this study was to search for potential diagnostic markers that are involved in immune cell infiltration for OS. Patients with OS who acquired metastases within 5 years (n = 34) were compared to patients who did not develop metastases within 5 years (n = 19). Differentially expressed genes (DEGs) were tested for in both patient groups. To discover possible biomarkers, the LASSO regression model and the SVM-RFE analysis were both carried out. With the assistance of CIBERSORT, the compositional patterns of the 22 different types of immune cell fraction in OS were estimated. In this research, a total of 33 DEGs were obtained: 33 genes were significantly downregulated. Moreover, we identified six critical genes, including ALOX5AP, HLA-DOA, HLA-DMA, HLA-DRB4, HCLS1 and LOC647450. ROC assays confirmed their diagnostic value with AUC > 0.7. In addition, we found that the six critical genes were associated with immune infiltration. Then, we confirmed the expression of ALOX5AP was distinctly decreased in OS specimens and cell lines. High expression of ALOX5AP predicted an advanced clinical stage and overall survival of OS patients. Functionally, we found that overexpression of ALOX5AP distinctly suppressed the proliferation, migration, invasion and EMT via modulating Wnt/ß-catenin signaling. Overall, we found that ALOX5AP overexpression inhibits OS development via regulation of Wnt/ß-catenin signaling pathways, suggesting ALOX5AP as a novel molecular biomarker for enhanced therapy of OS.

Overexpressed lncRNA LINC00893 Suppresses Progression of Colon Cancer by Binding with miR-146b-3p to Upregulate PRSS8.

Background: Long noncoding RNAs (lncRNAs) play a significant role in the progression and metastasis of various cancers. LINC00893 has been reported to exert antitumor effect on various cancers such as gastric cancer and thyroid cancer. Bioinformatics analysis also predicted that LINC00893 was downregulated in colon cancer. However, the clinical significance and regulating mechanism of LINC00893 in colon cancer remain unknown. Methods: Expression of LINC00893, miR-146b-3p, and PRSS8 was detected in colon cancer tissues and adjacent nontumor tissues by RT-qPCR, and clinical significance was analyzed by receiver operating characteristic curve. The regulatory mechanism of LINC00893, miR-146b-3p, and PRSS8 was investigated by dual luciferase reporter and RNA pull-down assays. Proliferation, migration, invasion, and apoptosis were measured in HCT116 and SW620 cells by MTT, EdU staining, wound healing, Transwell, TUNEL, and flow-cytometry assays. Moreover, the effect of LINC00893 on colon cancer progression was further evaluated in tumor-bearing mice. Results: LINC00893 and PRSS8 were significantly downregulated, while miR-146b-3p was upregulated in colon cancer tissues compared to control group. LINC00893, miR-146b-3p, and PRSS8 had significant diagnostic value with area under curve of 0.9383, 0.7300, and 0.9644, respectively. Overexpressed LINC00893 or silenced miR-146b-3p suppressed the proliferation, migration, and invasion while promoting apoptosis in colon cancer cells (HCT116, SW620). Moreover, miR-146b-3p overexpression reversed the inhibitory effect of LINC00893, while PRSS8 knockdown rescued the suppressive effect of miR-146b-3p inhibitor on malignant cell behaviors in colon cancer. Furthermore, the tumor growth in mice was significantly reduced by LINC00893 overexpression. Conclusion: LINC00893 overexpression suppressed the progression of colon cancer by binding with miR-146b-3p to upregulate PRSS8. LINC00893 and its downstream molecules miR-146b-3p and PRSS8 may serve as novel biomarkers and therapeutic targets of colon cancer, providing new treatment options and research approaches towards colon cancer.

MiR-1224 Acts as a Prognostic Biomarker and Inhibits the Progression of Gastric Cancer by Targeting SATB1.

OBJECTIVE: MiR-1224 has been reported to exhibit abnormal expression in several tumors. However, the expressing pattern and roles of miR-1224 in gastric cancer (GC) remain unclear. Our current research aimed to explore the potential involvement of miR-1224 in the GC progression. MATERIALS AND METHODS: The expression of miR-1224 was examined in tissue samples of 128 GC patients and cell lines by RT-PCR. Besides, the associations of miR-1224 expressions with clinicopathologic features and prognosis of GC patients were analyzed. Then, the possible influences of miR-1224 on cell proliferation and cell migration were determined. Afterward, the molecular target of miR-1224 was identified using bioinformatics assays and confirmed experimentally. Finally, RT-PCR and Western blot assays were performed to investigate the effect of the abnormal miR-1224 expression on the EMT and Wnt/ß-catenin pathway. RESULTS: miR-1224 was lowly expressed in the GC specimens and cell lines due to T classification and TNM stage. Survival assays demonstrated that GC patients with low expressions of miR-1224 possessed poor overall survivals. Moreover, in vitro and in vivo assays revealed that the overexpression of miR-1224 inhibited cell proliferation, migration, and invasion in GC cells. SATB homeobox 1 (SATB1) was verified as a direct target of miR-1224 in GC. Furthermore, ß-catenin and c-myc were significantly inhibited in miR-1224-overexpression cells. CONCLUSIONS: Our findings highlight the potential of miR-1224 as a therapeutic target and novel biomarker for GC patients.

miR­142­5p inhibits pancreatic cancer cell migration and invasion by targeting PIK3CA.

Pancreatic cancer is a fatal disease with a high mortality rate and poor prognosis worldwide. The aberrant expression of microRNAs (miRs) is associated with cancer development and progression. The present study aimed to evaluate the functional role of miR­142­5p in migration and invasion, and investigated its underlying molecular mechanism in pancreatic cancer cells. First, it was identified that miR­142­5p expression was downregulated in pancreatic cancer tissues and cell lines by reverse transcription­quantitative polymerase chain reaction. Furthermore, phosphoinositide­3­kinase catalytic subunit α (PIK3CA) was identified as a target of miR­142­5p. The expression of PIK3CA was upregulated in tumor tissues and its expression was negatively regulated by miR­142­5p expression. Notably, overexpression of miR­142­5p inhibited the proliferation, migration and invasion of PanC1 cells, while PIK3CA reversed this inhibition. In addition, miR­142­5p suppressed the expression of focal adhesion kinase (FAK) and matrix metalloproteinase (MMP)9, as well as phosphorylated protein kinase B (AKT) protein level, while PIK3CA reversed the suppression induced by miR­142­5p. In conclusion, miR­142­5p functions as a tumor suppressor, which inhibits the migration and invasion of pancreatic cancer by suppressing the expression of FAK and MMP9, as well as the phosphatidylinositol 3­kinase/AKT signaling pathway by targeting PIK3CA. These findings suggest that miR­142­5p may be a novel therapeutic target for the treatment of pancreatic cancer.

USP9X mRNA expression predicts clinical outcome for esophageal squamous cell carcinoma treated with cisplatin-based therapy.

INTRODUCTION: Combination therapy with cisplatin is the conventional first-line treatment in patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC). Ubiquitin-specific protease 9X (USP9X) has been shown to be associated with resistance to chemotherapy drugs in several cancers. The purpose of this study was to explore the predictive effects of USP9X on advanced ESCC patients treated with cisplatin-based regimens. MATERIALS AND METHODS: The subjects were 69 advanced ESCC patients who received first-line cisplatin-based chemotherapy or chemoradiotherapy. The quantitative real-time PCR was performed to measure USP9X mRNA expression. The correlation of USP9X expression with clinical parameters and tumor response was analyzed. The Kaplan-Meier method and Cox analysis were employed to analyze differences in overall survival (OS). RESULTS: USP9X mRNA expression was positively associated with the TMN stage at initial diagnosis. Patients with low USP9X mRNA expression had a significantly higher objective response rate (57.1% vs. 17.6%, P=0.001) and longer median OS (25.0 vs. 14.0 months, P<0.001) than those with high expression in all patients or in different treatment subgroups (all P<0.05). Multivariate analysis showed that low mRNA expression of USP9X emerged as an independent prognostic factor indicating prolonged OS (hazard ratio 0.50, 95% CI 0.34-0.73; P<0.001). CONCLUSION: These findings suggest that high USP9X mRNA expression predicts poor clinical efficacy and survival to cisplatin-based therapy in patients with advanced ESCC.

miR-142-5p regulates pancreatic cancer cell proliferation and apoptosis by regulation of RAP1A.

Pancreatic cancer, one of the fatal and aggressive malignancies, leads the sixth cancer-associated death in China. microRNAs are believed to exert function in the diagnosis and treatment of pancreatic cancer. In the present study, we firstly found that miR-142-5p was downregulated in pancreatic cancer tumor tissues while Ras-related protein Rap-1 A (RAP1A) was upregulated compared with para-carcinoma non-tumor tissues. Then, we found that RAP1A could be a putative target gene of miR-142-5p by bioinformatics tool TargetScan. Furthermore, we conducted luciferase reporter assay, RT-qPCR, western blot and correlation analysis to demonstrate that miR-142-5p could negatively regulate RAP1A expression by binding to its 3'UTR. In addition, cell-counting kit 8 (CCK-8) and flow cytometry assays certified that miR-142-5p overexpression may inhibit pancreatic cancer cell proliferation but promote cell apoptosis; while the variation could be reversed by co-transfected with pcDNA3.1-RAP1A. Finally, miR-142-5p overexpression downregulated p-ERK1/2, phosphate p38 mitogen-activated protein kinases (p-p38); however, the variation induced by miR-142-5p mimic could be reversed by co-transfected with pcDNA3.1-RAP1A. In conclusion, our findings indicate that targeting miR-142-5p may provide a novel strategy for the treatment of pancreatic cancer.

Positive feedback loop of lncRNA LINC01296/miR-598/Twist1 promotes non-small cell lung cancer tumorigenesis.

Emerging evidence has illustrated the vital roles of long noncoding RNAs (lncRNAs) in human cancers. However, the role of lncRNAs in non-small cell lung cancer (NSCLC) is still elusive and poorly understood. In the current study, our team conducted extensive experiments to identify the role of long intergenic nonprotein coding (LINC01296) on NSCLC tumorigenesis. The results illustrated that the elevated LINC01296 expression in NSCLC tissue specimens and cell lines were closely correlated with the poor prognosis of patients with NSCLC. Functional studies revealed that LINC01296 knockdown silenced by small interfering RNAs inhibited proliferation, accelerated apoptosis in vitro, and impaired tumor growth in vivo. Mechanical studies showed that INC01296 harbored miR-598, acting as a microRNA "sponge." Besides, miR-598 targeted the 3'-UTR of Twist1. Interestingly, transcription factor Twist1 could bind with the promoter of INC01296 and activate its transcriptional level. In summary, we conclude that INC01296/miR-598/Twist1 constitutes a positive feedback loop to promote the tumorigenesis of NSCLC, providing a novel insight and a valuable therapeutic strategy.

ZNF418 overexpression protects against gastric carcinoma and prompts a good prognosis.

BACKGROUND: This study aimed to investigate the prognostic power of zinc-finger protein 418 (ZNF418) in gastric cancer (GC) and its potential role in GC development and progression. PATIENTS AND METHODS: A total of 10 GC patients' individual plasmas were collected and screened for dysregulated mRNA using human microarray. Among these dysregulated mRNAs, ZNF418 was found to be significantly downregulated in IIIA-IV stage GC patients compared to IA-IIA stage GC patients. Subsequently, the ZNF418 levels were detected by quantitative reverse transcription-polymerase chain reaction in both GC plasmas and tissues in a larger sample, and the association between ZNF418 expression level and clinicopathological features as well as overall survival (OS) of GC patients was further analyzed. Finally, a network of ZNF418 interactions with other molecules was predicated in STRING and GEPIA databases. RESULTS: Human mRNA microarray was performed to screen for abnormally expressed mRNAs between five IIIA-IV stage GC patients' plasma and five IA-IIA stage GC patients' plasma. A total of 662 mRNAs were differentially expressed in the IIIA-IV stage GC plasma vs IA-IIA stage GC plasma among all the candidate mRNAs according to the Student's t-test. Results showed that a decrease in the ZNF418 expression level was associated with the presence of GC and also with higher tumor-node-metastasis stage and lower OS rates compared with that in adjacent noncancerous tissues. Cox regression analysis results demonstrated that the OS was independently correlated with ZNF418 expression. Finally, the prediction results showed that a total of eight mRNAs might have an interaction with ZNF418 in both STRING and GEPIA databases. CONCLUSION: ZNF418 was first identified to be significantly downregulated in GC. Our study indicated that ZNF418 might serve as a novel biomarker for GC and was involved in GC development.

[Characteristics of Enteromorpha prolifera Biochars and Their Adsorption Performance and Mechanisms for Cr(â ¥)].

This study aims to understand the recycling process of Enteromorpha prolifera by using the slow pyrolysis technology to prepare biochars under different temperatures and by characterizing the physicochemical properties of biochars. The results showed that a relatively high level pyrolysis of Enteromorpha prolifera could be reached when the temperature was up to 400℃. The yield rate and the ash content of biochars were negatively correlated with the pyrolysis temperature, while the carbon content was positively correlated. The specific surface area of Enteromorpha prolifera biochars was in the range of 44.54-317.82 m2·g-1. The biochar surface was in the shape of a honeycomb and rich in oxygen-containing functional groups, such as hydroxyl (-OH) and carboxyl (-COOH) groups. The adsorption experiments revealed that the adsorption of Cr(Ⅵ) onto Enteromorpha prolifera biochars followed the pseudo-second-order kinetics equation and Langmuir isotherm, indicating that the adsorption process was controlled by the fast reaction process and governed by monomolecular and chemical adsorption. The optimal pH for Cr(Ⅵ) adsorption onto Enteromorpha prolifera biochars was 2 and their adsorption capabilities were in the order of BC400 > BC700 > BC600 > BC500 > BC300 (the adsorption capacity of BC400 was 4.79 mg·g-1). The adsorption mechanism included the electrostatic interactions between biochar and anions (HCrO-4 and Cr2O2-7) and the complexation of oxygen-containing functional groups.

Epigenetic activation of SIN1 promotes NSCLC cell proliferation and metastasis by affecting the epithelial-mesenchymal transition.

Stress-activated protein kinase (SAPK) interacting protein 1 (SIN1) is an essential component of mTORC2. Previous studies have shown that SIN1 is a key regulator of Akt pathway which plays an important role in various pathological conditions including cancer. While its effects and mechanisms on the progression of NSCLC remain unknown. In this study, we report that SIN1 is able to promote the growth and migration of NSCLC cells both in vitro and in vivo. Overexpression of SIN1 promoted A549 and H1299 cells proliferation by both MTT and colony formation assays. Consistently, knockdown of SIN1 inhibited the proliferation of these cells. In transwell assay, overexpression of SIN1 increased the migration of A549 and H1299 cells, while SIN1 knockdown reduced their migration. In a tumor xenograft model, overexpression of SIN1 promoted tumor growth of A549 cells in vivo, while SIN1 knockdown suppresses the tumor growth. We also found a mechanistic link between SIN1 and H3K4me3, H3K4me3 is involved in SIN1 upregulation. Moreover, SIN1 can significantly promote the in vitro migration and invasion of NSCLC cells via induction epithelial mesenchymal transition (EMT) process, which subsequently leads to transcriptional downregulation of epithelial marker E-cadherin and upregulation of mesenchymal markers N-cadherin and Vimentin expression. Together, our results reveal that SIN1 plays an important role in NSCLC and SIN1 is a potential biomarker and a promising target in the treatment of NSCLC.

[Comparison of the efficacy and safety of capecitabine or tegafur, gimeracil and oteracil potassium capsules combined with oxaliplatin chemotherapy regimens in the treatment of advanced gastric cancer].

OBJECTIVE: To observe the efficacy and safety of chemotherapy regimens oxaliplatin combined with capecitabine (CAPOX) or oxaliplatin combined with tegafur, gimeracil and oteracil potassium capsules (S-1)(SOX), and to investigate the value of expression of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) proteins in tumor tissue for predicting the efficacy of CAPOX and SOX regimens in advanced gastric cancer patients. METHODS: A total of 107 newly-diagnosed, stage Ⅲc/Ⅳ gastric cancer patients (no surgical indication, ECOG performance scores 0-2 and expected survival time ≥3 months) were recruited with 101 patients evaluated. The patients were randomly divided into two groups. One was study group in which the patients received CAPOX regimen. The other was control group received SOX regimen. Each patient received four cycles, at least two cycles chemotherapy every three weeks and followed up until death or lost. Tumor biopsies were obtained by gastroscopy for immunohistochemical examination of the expression of TP and DPD proteins before chemotherapy. Response rate (ORR), overall survival (OS) and time to tumor progression (TTP) of the patients were assessed. RESULTS: The objective response rate (ORR) of the study and control groups was 49.0% (5/51) vs. 46.0% (23/50), respectively (P>0.05). The overall survival (OS) was 357.36±24.69 days in the study group and 349.87±22.63 days in the control group, and the time-to-progression (TTP) was 216.75±19.32 days in the study group and 220.54±18.47 days in the control group (P>0.05 for both). Stratified analysis showed that the ORR of TP-positive patients in the study group was significantly higher than that in the control group (72.0 % vs. 41.7 %, P=0.032). There was no significant difference in ORR between the TP-negative patients in the study and control groups (26.9% vs. 50.0%, P=0.087), while the ORR of DPD-positive patients in the control group was significantly higher than that of the study group (51.9% vs. 34.6%, P=0.046). There was no significant difference in the ORR between DPD-negative patients in the study and control groups (64.0% vs. 39.1%, P=0.084). The follow-up showed that the OS (378.42±22.56 days) and TTP (271.77±24.92 days) in the TP-positive patients of the study group were significantly longer than those of the control group (OS: 326.57±19.84 days, and TTP: 229.13±22.68 days)( P<0.05). The OS was 371.25±23.97 days and TTP was 264.66±21.36 days in the DPD-positive patients of control group, significantly longer than those of the study group (OS: 334.73±21.47days, and TTP: 208.58±20.70 days) (P<0.05). But there was no significant difference in the OS and TTP between the TP- and DPD-negative patients in the two groups (P>0.05). In respect of adverse events, both the rates of hematological and non-hematological toxicities were low and similar between the two groups (P>0.05), and well-tolerated by the patients. CONCLUSIONS: Both CAPOX and SOX regimens are effective chemotherapeutic protocols in treatment of patients with advanced gastric cancer. The expression levels of TP and DPD in tumor tissue can be used as a predictive factor for the efficacy of capecitabine or tegafur, gimeracil and oteracil potassium capsules combined with oxaliplatin regimens. CAPOX chemotherapy regimen is more suitable for the TP-positive gastric cancer patients, and SOX regimen is more suitable for the DPS-positive gastric cancer patients.

[Characterization of Cr Tolerance and Accumulation in Lolium perenne L. and Pharibitis purpurea(L.) Voigt].

Considering the serious pollution of heavy metal-chromium (Cr) in soil, there is an urgent need for effective selection of Cr-tolerant plant species. In order to gain fundamental insights into the tolerance and accumulation capabilities of Lolium perenne L. and Pharibitis purpurea(L.) Voigt under Cr stress, a pot experiment was conducted to investigate their growth, physiology and accumulation characteristics under Cr(Ⅲ) and Cr(Ⅵ) stress. The results showed the growth parameters could intuitively reflect the toxicity levels of Cr for plants. For instance, a low-level Cr(Ⅲ) (<250 mg·kg-1) in soil was good for plant growth as indicated by the significant elevation of plant height, root length and biomass in L. perenne (P<0.05). However, Cr(Ⅵ) at all concentrations (≥25 mg·kg-1) in the soil inhibited the growth of both plant species, and the root length was particularly sensitive to the toxicity of Cr. The physiological parameters of plant represented both the toxicity of Cr and the tolerance of plants under Cr stress. A decrease of root activity and an increase of malonaldehyde content were observed under Cr stress, which indicated the physiological metabolism of plants was disturbed. In the presence of both Cr species, the proline content increased, which served as an indicator for both high Cr toxicity and increase of osmotic balance in plants. A rise in SOD and POD activity reflected the defense ability of plants against oxidative stress caused by Cr. In addition, the Cr-accumulation related parameters were the major standards for tolerant species selection. The Cr(Ⅵ) accumulation capacities of both plant species were greater than their Cr(Ⅲ) accumulation capacities. The maximum accumulation amounts of L. perenne and P. purpurea reached 957.4 mg·kg-1 and 743.3 mg·kg-1 in roots and 394.7 mg·kg-1 and 340.4 mg·kg-1 in shoots, respectively. In comparison with P. purpurea, L. perenne displayed a stronger Cr accumulation capacity in roots with a maximum bioaccumulation factor of 15.55. However, the transport ability of P. purpurea was superior to L. perenne. All of the parameters demonstrated that both L. perenne and P. purpurea could be used as alternative plants for phytoremediation of Cr-contaminated soil.

MicroRNA-206 attenuates tumor proliferation and migration involving the downregulation of NOTCH3 in colorectal cancer.

Colorectal cancer (CRC) is the most common cancer diagnosed worldwide, and the development of metastases is a major cause of mortality. Accumulating evidence suggests that microRNAs are important in carcinogenesis by affecting the expression of genes that regulate cancer progression. A number of studies have shown that miR-206 is frequently downregulated in many human malignancies, including CRC, and is associated with a more malignant phenotype. Previous studies involving HeLa and C2C12 cells have validated the inhibitory mechanism of miR-206 via NOTCH3 targeting. However, whether or not the interplay between miR-206 and NOTCH3 also occurs in CRC is unknown. Therefore, we investigated the tumor suppressive and metastatic effects of miR-206 and its target, NOTCH3, in CRC. Based on the inverse association between the expression of miR-206 and NOTCH3 in CRC tissues, miR-206 mimics were transiently transfected into the SW480 (and its metastatic strain) and SW620 colon cancer cell lines. Upregulation of miR-206 inhibited cancer cell prolife-ration and migration, blocked the cell cycle, and activated apoptosis. The tumor suppressive capacity of miR-206 had a similar effect on CRC cells, although with a different metastatic potential, and may be explained by direct NOTCH3 signaling inhibition and indirect cross-talk with other signaling pathways involving CDH2 and MMP-9. These results support miR-206 as a tumor suppressor in CRC and suggest a potential therapeutic target for clinical intervention.

[The correlation between chemotherapeutic efficacy and breast cancer susceptibility gene 1 and class IIIß-tubulin protein expression in non-small cell lung cancer patients].

OBJECTIVE: To investigate the predictive value of breast cancer susceptibility gene 1 (BRCA1) and class IIIß-tubulin protein expression in tumor tissue for the efficacy of taxol and cisplatin combined chemotherapy (TP) in stage IIIB/IV non-small cell lung cancer (NSCLC) patients. METHODS: A total of 92 stage IIIB/IV NSCLC patients were recruited with 87 patients evaluated. Bronchoscopy or lung puncture tumor biopsy samples were obtained with BRCA1 and class IIIß-tubulin protein expression examined immunohistochemically before chemotherapy. The patients were randomly assigned to be received 4 to 6 cycles of TP chemotherapy regiments and followed up until death or lost. Response rate (RR), overall survival (OS) and time to tumor progression (TTP) were assessed. RESULTS: Among the 87 evaluated patients, the positive expression rates of BRCA1 and class IIIß-tubulin were 57.5% (50/87) and 48.3% (42/87) respectively. There was no significant difference in clinical characteristics among patients with different positive expression rate. According to different expression of BRCA1 and class IIIß-tubulin, the patients were divided into four groups: group A (low expression of both BRCA1 and class IIIß-tubulin), group B (high expression of both BRCA1 and class IIIß-tubulin), group C (high expression of only BRCA1) and group D (high expression of only class IIIß-tubulin). The RR was higher in group A than other three groups (60.7%, 34.8%, 9/19 and 6/17 respectively). The OS and TTP were longer in group A than other three groups [OS: (539.4 ± 17.6) days, (267.2 ± 20.5) days, (325.6 ± 24.1) days and (283.7 ± 26.2) days respectively; TTP: (256.9 ± 28.4) days, (143.8 ± 17.6) days, (179.3 ± 19.8) days and (152.6 ± 23.5) days respectively]. There were no significant differences among the other three groups. CONCLUSIONS: The expression level of BRCA1 and class IIIß-tubulin in tumor tissue is probably a predictor for the efficacy of TP chemotherapy in NSCLC patients. TP chemotherapy is more suitable for the NSCLC patients with lower expression of both BRCA1 and class IIIß-tubulin. Our study may provide a new sight for tailored chemotherapy in NSCLC patients.