Dynamic analysis of circulating tumor DNA to predict the prognosis and monitor the treatment response of patients with metastatic triple-negative breast cancer: A prospective study.

Background: Limited data are available on applying circulating tumor DNA (ctDNA) in metastatic triple-negative breast cancer (mTNBC) patients. Here, we investigated the value of ctDNA for predicting the prognosis and monitoring the treatment response in mTNBC patients. Methods: We prospectively enrolled 70 Chinese patients with mTNBC who had progressed after ≤2 lines of chemotherapy and collected blood samples to extract ctDNA for 457-gene targeted panel sequencing. Results: Patients with ctDNA+, defined by 12 prognosis-relevant mutated genes, had a shorter progression-free survival (PFS) than ctDNA- patients (5.16 months vs. 9.05 months, p=0.001), and ctDNA +was independently associated with a shorter PFS (HR, 95% CI: 2.67, 1.2-5.96; p=0.016) by multivariable analyses. Patients with a higher mutant-allele tumor heterogeneity (MATH) score (≥6.316) or a higher ctDNA fraction (ctDNA%≥0.05) had a significantly shorter PFS than patients with a lower MATH score (5.67 months vs.11.27 months, p=0.007) and patients with a lower ctDNA% (5.45 months vs. 12.17 months, p<0.001), respectively. Positive correlations with treatment response were observed for MATH score (R=0.24, p=0.014) and ctDNA% (R=0.3, p=0.002), but not the CEA, CA125, or CA153. Moreover, patients who remained ctDNA +during dynamic monitoring tended to have a shorter PFS than those who did not (3.90 months vs. 6.10 months, p=0.135). Conclusions: ctDNA profiling provides insight into the mutational landscape of mTNBC and may reliably predict the prognosis and treatment response of mTNBC patients. Funding: This work was supported by the National Natural Science Foundation of China (Grant No. 81902713), Natural Science Foundation of Shandong Province (Grant No. ZR2019LZL018), Breast Disease Research Fund of Shandong Provincial Medical Association (Grant No. YXH2020ZX066), the Start-up Fund of Shandong Cancer Hospital (Grant No. 2020-PYB10), Beijing Science and Technology Innovation Fund (Grant No. KC2021-ZZ-0010-1).

Targeting kinesin family member 21B by miR-132-3p represses cell proliferation, migration and invasion in gastric cancer.

Recently, kinesin family member 21B (KIF21B) has been reported to be an oncogene in non-small cell lung cancer and hepatocellular carcinoma. However, the functional role of KIF21B and related molecular mechanisms in gastric cancer (GC) remain largely uncovered. In this study, online bioinformatics analysis showed that KIF21B was overexpression in GC and predicted poor prognosis. Consistently, we found that the protein expression of KIF21B was upregulated in GC tissues compared with adjacent tissues by immunohistochemistry. Knockdown of KIF21B significantly suppressed cell proliferation, migration and invasion in GC cell lines (AGS and SNU-5) using Cell counting kit­8 (CCK-8) assay, colony formation and transwell assay. KIF21B was confirmed as the target of miR-132-3p in GC cells by luciferase reporter assay. Moreover, miR-132-3p was down-regulated and KIF21B expression was upregulated in GC tissues. Overexpression of KIF21B reversed the miR-132-3p-mediated suppressive effects on GC cell proliferation, migration and invasion. Furthermore, miR-132-3p overexpression downregulated the protein levels of Wnt1, c-Myc, ß-catenin, proliferating cell nuclear antigen (PCNA) and N-cadherin, and upregulated E-cadherin expression in GC cells, which were all alleviated after KIF21B overexpression. In conclusion, our findings indicate that down-regulation of KIF21B by miR-132-3p suppresses cellular functions in GC, which might be linked to reduced Wnt/ß-catenin signaling.

Novel Tumor-Specific Antigens for Immunotherapy Identified From Multi-omics Profiling in Thymic Carcinomas.

Thymic carcinoma (TC) is the most aggressive thymic epithelial neoplasm. TC patients with microsatellite instability, whole-genome doubling, or alternative tumor-specific antigens from gene fusion are most likely to benefit from immunotherapies. However, due to the rarity of this disease, how to prioritize the putative biomarkers and what constitutes an optimal treatment regimen remains largely unknown. Therefore, we integrated genomic and transcriptomic analyses from TC patients and revealed that frameshift indels in KMT2C and CYLD frequently produce neoantigens. Moreover, a median of 3 fusion-derived neoantigens was predicted across affected patients, especially the CATSPERB-TC2N neoantigens that were recurrently predicted in TC patients. Lastly, potentially actionable alterations with early levels of evidence were uncovered and could be used for designing clinical trials. In summary, this study shed light on our understanding of tumorigenesis and presented new avenues for molecular characterization and immunotherapy in TC.

Molecular Characteristics, Clinical Implication, and Cancer Immunity Interactions of Pyroptosis-Related Genes in Breast Cancer.

Objective: Pyroptosis represents an emerging inflammatory form of programmed cell death. Herein, specific functions and clinical implications of pyroptosis-related genes were systematically characterized in breast cancer. Methods: Expression, somatic mutation and copy number variation of 33 pyroptosis-related genes were assessed in breast cancer from TCGA dataset. Their interactions, biological functions and prognostic values were then observed. By stepwise Cox regression analysis, a pyroptosis-related gene signature was generated. The predictive efficacy in survival was examined by survival analyses, ROCs, univariate and multivariate analyses and subgroup analyses. Associations between risk score (RS) and cancer immunity cycle, HLA, immune cell infiltrations, and immune checkpoints were analyzed. Results: Most of pyroptosis-related genes were abnormally expressed in breast cancer. CASP8, NLRC4, NLRP3, NLRP2, PLCG1, NLRP1, NLRP7, SCAF11, GSDMC, and NOD1 occurred somatic mutations as well as most of them had high frequency of CNV. There were closely interactions between them. These genes were distinctly enriched in immune-related processes. A three-gene signature was generated, containing IL-18, GSDMC, and TIRAP. High RS predicted poorer overall survival, progression, and recurrence. After verification, this RS was an independent and sensitive predictive index. This RS was negatively correlated to cancer immunity cycle. Also, low RS was characterized by high HLA, immune cell infiltrations and immune checkpoints. A nomogram including age and RS was generated for accurately predicting 5-, 8-, and 10-year survival probabilities. Conclusion: Pyroptosis-related genes exert key roles in cancer immunity and might be applied as a prognostic factor of breast cancer.

Experimental study of the effect of typical halides on pyrolysis of ammonium nitrate using model reconstruction.

The energetic material ammonium nitrate (AN) is used as an industrial raw material; however, it presents a pyrolysis and explosion hazard during transportation and storage, especially when mixed with impurities. To study the effects of typical halides on the thermal decomposition kinetics of AN, a series of precision thermogravimetric analysis experiments at four heating rates were carried out in a nitrogen atmosphere. Based on derivative thermogravimetric analysis, the addition of sodium halides was found to change the kinetic reaction mechanism of AN pyrolysis. The activation energies were obtained using the isoconversional method, and the pre-exponential factor was derived from the kinetic compensation effect. Models of the kinetic reaction mechanism were reliably reconstructed by combining composite kinetic data processing methods, namely, model-free method, model-fitting method, and parameter simulation. A comprehensive analysis showed that the addition of sodium halides shifts the kinetic mechanism of the pyrolysis of AN toward different dominant reaction models (such as reaction order models, power law models, or phase boundary control models) than those of the original reaction model. The results are helpful as a reference and provide guidance for the determination of AN pyrolysis behavior and the simulation of parameters.

Using proteomic profiling to characterize protein signatures of different thymoma subtypes.

BACKGROUND: Histology is a traditional way to classify subtypes of thymoma, because of low cost and convenience. Yet, due to the diverse morphology of thymoma, this method increases the complexity of histopathologic classification, and requires experienced experts to perform correct diagnosis. Therefore, in this study, we developed an alternative method by identifying protein biomarkers in order to assist clinical practitioners to make right classification of thymoma subtypes. METHODS: In total, 204 differentially expressed proteins in three subtypes of thymoma, AB, B2, and B3, were identified using mass spectrometry. Pathway analysis showed that the differentially expressed proteins in the three subtypes were involved in activation-related, signaling transduction-related and complement system-related pathways. To predict the subtypes of thymoma using the identified protein signatures, a support vector machine algorithm was used. Leave-one-out cross validation methods and receiver operating characteristic analysis were used to evaluate the predictive performance. RESULTS: The mean accuracy rates were > 80% and areas under the curve were ≧0.93 across these three subtypes. Especially, subtype B3 had the highest accuracy rate (96%) and subtype AB had the greatest area under the curve (0.99). One of the differentially expressed proteins COL17A2 was further validated using immunohistochemistry. CONCLUSIONS: In summary, we identified specific protein signatures for accurately classifying subtypes of thymoma, which could facilitate accurate diagnosis of thymoma patients.

An experimental and theoretical study of optimized selection and model reconstruction for ammonium nitrate pyrolysis.

Ammonium nitrate (AN) is a commonly-used industrial raw material in industrial explosives and fertilizers areas. However, as an energetic material, its danger exists during the production, transportation, and storage, resulting in a large number of accidents involving personal injury and property loss. To obtain the accurate kinetic triplet parameters of AN thermal decomposition, a series of thermogravimetry analysis (TGA) experiments was conducted with four different heating rates. Activation energies were calculated by different isoconversional methods Then the kinetic triplet of AN pyrolysis was optimized using a combination of experimental and simulant methods. Combined with the traditional model-free and model-fitting approaches, the experimental kinetic model for AN pyrolysis was optimized and then reconstructed. Through the pyrolysis reaction of AN, a reliable methodology for processing TGA data of hazardous material is proposed in the paper, and the kinetic parameters can be accurately obtained by using such a kinetics method.

Transcription activated p73-modulated cyclin D1 expression leads to doxorubicin resistance in gastric cancer.

Gastric cancer (GC) is one of the leading types of cancer in terms of mortality cases worldwide. Doxorubicin (Dox), a common chemotherapy drug, is frequently used to treat GC; however, acquired resistance to Dox hinders the chemotherapeutic outcome and causes shorter survival in GC patients. Several Dox-resistant GC cell lines, including SGC7901, SNU-1 and SNU-5 were generated to investigate the mechanism of Dox resistance in GC. Various methods were used to test the response of Dox-resistant GC cells and parental cells, including flow cytometry, Cell Counting kit-8 assay, reverse transcription polymerase chain reaction and western blot analysis. In the present study, various Dox-resistant cells presented reduced apoptosis and cell cycle arrest in response to Dox treatment. Western blot results revealed that cyclin D1 was upregulated in Dox-resistant cells, whereas inhibition or depletion of cyclin D1 re-sensitized the resistant cells to Dox treatment, which indicated that the induction of cyclin D1 expression was a result of the Dox resistance in GC cells. Furthermore, it was observed that a transcription activated form of p73 (TAp73), is the upstream modulator of cyclin D1, manipulating the cyclin D1 transcription with the assistance of activator protein 1 (AP-1). Overall, the present study data provided a rational strategy to overcome the Dox resistance in GC treatment by inhibiting cyclin D1 expression.

Expression of TAp73α affects the therapy effect of chemotherapy drugs in gastric cancer.

The transcription factor TAp73, a transcriptionally active isoform of p73, has high structure and function similaritieswith its homolog p53, therefore, are thought to be a cancer therapy candidate target. However, there is still a controversy about the tumor suppressor role of TAp73, since it has been found in numerous studies that TAp73 expression is elevated in different cancers. Thus, we take effort to clarify the influence of TAp73 on gastric cancer (GC) chemotherapy. Multiple cell lines of GC such as SNU-1, SNU-3, and AGS were applied to investigate expression of TAp73. Flow cytometry was utilized to detect apoptosis, revealing how TAp73 overexpression affected anticancer drug (ACD). Additionally, we explored how TAp73 overexpression influenced apoptotic cells of neoplastic tissues and tumor size of nude mice in vivo. Our results indicated that TAp73 was down-regulated in GC cells after chemotherapy drugs treatment. Besides, enforced expression of TAp73 affects chemotherapeutic drugs induced GC cell apoptosis, which is dependent on p53. The expression of TAp73 was regulated by its transcription factor, E2F1, in response to chemotherapy drugs. Our in vivo xenograft results also suggested that transfection of TAp73 affects the tumor suppression effect of 5-FU. Consequently, the findings of our study demonstrate that E2F1 and TAp73α are oncogenic and throw light upon the underlying mechanism of their role against apoptosis.

A missense variant in EZH2 is associated with colorectal cancer risk in a Chinese population.

Colorectal cancer (CRC) ranks the fifth leading cause of cancer death in China. EZH2 is a member of Polycomb-group (PcG) family and associated with transcriptional repression and cancer development. In this study, we report the association between a missense variant in EZH2 and risk of CRC. Through a systematic selection of variants in EZH2, we identified rs2302427 in the exon region of EZH2 and genotyped this variant in 852 CRC patients and 1,303 healthy controls using Taqman genotyping assay. The association between this variant and CRC risk was calculated using logistic regression with adjustment of sex, age, smoking status and drinking status. The result showed that rs2302427 was significantly associated with CRC susceptibility under an additive model (P=0.0068). Compared with CC genotype carriers, CG genotype and GG genotype carriers were associated with risk of CRC with odds ratio being 0.78 (95% CI: 0.63-0.96, P=0.0198) and 0.54 (95% CI: 0.24-1.18, P=0.1224), respectively. When stratified by sex, age, smoking status or drinking status, significant associations were observed only in younger individuals (OR=0.67, 95% CI: 0.50-0.89, P=0.0067) or smokers (OR=0.65, 95% CI: 0.48-0.88, P=0.0051). This study provides new insights into the personalized prevention of colorectal cancer.

Cold Exposure Differentially Stimulates Angiogenesis in BAT and WAT of Mice: Implication in Adrenergic Activation.

BACKGROUND/AIMS: To characterize the temporal profile of cold-induced angiogenesis in brown and white adipose tissues of mice in vivo and the temporal changes of angiogenic factors in primary mice brown (BA) and white adipocytes (WA) treated with ß3-adrenoceptor agonist (CL316,243) in vitro. METHODS: 8-week old male C57BL/6J mice were individually housed in conventional cages under cold exposure (4°C) for 1, 2, 3, 4 and 5 days. Interscapular brown adipose tissue (iBAT), inguinal subcutaneous (sWAT) and epididymal white adipose tissues (eWAT) were harvested for immunohistochemical and gene expression analysis. In vitro, primary mice BA and WA treated with or without CL316,243 were harvested for gene expression and protein secretion analysis. RESULTS: A combination of morphological and genetic (Vegfa, Vegfr2, Hif-1α, Pai1 and Pedf) analyses demonstrated depot-specific angiogenesis in response to cold exposure. Upon CL316,243 treatment, angiogenic factors (Vegfa, Vegfr2, Hif-1α, Pai1 and Pedf) and secreted protein VEGFA were transiently increased in both BA and WA. CONCLUSION: Our results show that iBAT is highly responsive to cold-induced angiogenesis that is mainly supported by sWAT with a lesser extent by eWAT. Moreover, the angiogenesis is a transient process with the angiogenic factors may work in an autocrine/paracrine manner.

Direct repression of the oncogene CDK4 by the tumor suppressor miR-486-5p in non-small cell lung cancer.

MicroRNAs are a class of non-coding single-stranded RNA, 20-23 nucleotide in length, which can be involved in the regulation of gene expression. Through binding with 3'-untranslated regions (3'-UTR), microRNAs can cause degradation of target mRNAs or inhibition of translation, and thus regulating the expression of genes at the post-transcriptional level. In this study, we found that miR-486-5p was significantly downregulated in non-small cell lung cancer (NSCLC) tissues and cell lines, suggesting that miR-486-5p might function as a tumor suppressor in lung cancer. Additionally, we showed that CDK4, an oncogene that plays an important role in cell cycle G1/S phase progression, was directly targeted by miR-486-5p. Furthermore, our data reveals that knockdown of CDK4 by siRNA can inhibit cell proliferation, promote apoptosis, and impede cell-cycle progression. In epigenetics, the upstream promoter of miR-486-5p was strongly regulated by methylation in NSCLC. Collectively, our results suggest that miR-486-5p could not only inhibit NSCLC by downregulating the expression of CDK4, but also be as a promising and potent therapy in the near future.

Adult asymptomatic hamartoma in the distal esophagus: a rare case.

An esophageal hamartoma is a rare, benign germ-cell condition. Most hamartomas are intraluminal tumors located in the upper third of the esophagus. We herein report an unusual case of a pedunculated hamartoma that involved the lower third of the esophagus that was diagnosed incidentally during investigations for epigastric pain. The features noted on endoscopy, endoscopic ultrasound/Doppler endoscopic ultrasound and computed tomography of the chest are also presented.

MicroRNA-199a-5p affects porcine preadipocyte proliferation and differentiation.

MicroRNAs (miRNAs), a class of small non-coding RNAs, have emerged as novel and potent regulators of adipogenesis. However, few miRNAs have been fully investigated in porcine adipogenesis, given the fact that pig is not only an apropos model of human obesity research, but also a staple meat source of human diet. In this study, we showed that miRNA-199a-5p is highly expressed in porcine subcutaneous fat deposits compared to several other tissue types and organs measured alongside. Overexpression of miR-199a-5p in porcine preadipocytes significantly promoted cell proliferation while attenuating the lipid deposition in porcine adipocytes. By target gene prediction and experimental validation, we demonstrated that caveolin-1 (Cav-1) may be a bona fide target of miR-199a-5p in porcine adipocytes, accounting for some of miR-199a-5p's functions. Taken together, our data established a role of miR-199a-5p in porcine preadipocyte proliferation and differentiation, which is at least partially played by downregulating Cav-1.

[Comparison of two quantitation methods of circulating tumor cells in patients with small cell lung cancer].

OBJECTIVE: To establish a quantitative method to detect circulating tumor cells (CTC) in patients with small cell lung cancer, and analyze its sensitivity and stability. METHODS: A specific primer and probe for prepro-gastrin-releasing peptide (preproGRP) was designed and a quantitative RT-PCR method was established to detect preproGRP mRNA. Cell incorporation method was used to evaluate the sensitivity. Magnetic cell sorting (MACS) was used to isolate and purify CTC from peripheral blood, and the MACS in combination with morphological diagnosis were used for cell counting. RESULTS: The isolation rate of CTC by MACS was 30% and the lower detection limit was 5 cells per ml blood. The sensitivity of quantitative RT-PCR in detection of preproGRP mRNA in CTC was 0.64 cells per reaction, and the lower detection limit was 50 cells per ml blood, which was lower than that of MACS. However, the cell numbers calculated by Ct value was in greater accordance (about 80%) with actual cell numbers than that obtained by MACS. CONCLUSIONS: PreproGRP quantitative RT-PCR and MACS have both advantages and disadvantages in detecting CTC of SCLC patients. MACS has a higher sensitivity, and is more favorable when CTC count is below 50 per ml blood. Meanwhile, preproGRP mRNA quantitative RT-PCR is more reliable in calculating actual cell numbers.

MiRNA-199a-3p regulates C2C12 myoblast differentiation through IGF-1/AKT/mTOR signal pathway.

MicroRNAs constitute a class of ~22-nucleotide non-coding RNAs. They modulate gene expression by associating with the 3' untranslated regions (3' UTRs) of messenger RNAs (mRNAs). Although multiple miRNAs are known to be regulated during myoblast differentiation, their individual roles in muscle development are still not fully understood. In this study, we showed that miR-199a-3p was highly expressed in skeletal muscle and was induced during C2C12 myoblasts differentiation. We also identified and confirmed several genes of the IGF-1/AKT/mTOR signal pathway, including IGF-1, mTOR, and RPS6KA6, as important cellular targets of miR-199a-3p in myoblasts. Overexpression of miR-199a-3p partially blocked C2C12 myoblast differentiation and the activation of AKT/mTOR signal pathway, while interference of miR-199a-3p by antisense oligonucleotides promoted C2C12 differentiation and myotube hypertrophy. Thus, our studies have established miR-199a-3p as a potential regulator of myogenesis through the suppression of IGF-1/AKT/mTOR signal pathway.

Proteome analysis and tissue array for profiling protein markers associated with type B thymoma subclassification.

BACKGROUND: The prognostic relevance of World Health Organization (WHO) subtypes within type B thymomas is still controversial. Understanding of the molecular characteristics of the different histologic types of thymomas will provide meaningful information for diagnosis and therapeutic management in type B thymoma. METHODS: Proteins extracted from twelve type B thymoma tissue specimens (six type B1 and six type B2) were analyzed by two-dimensional electrophoresis (2-DE) coupled with MALDI-TOF-MS. Differentially expressed proteins were then assayed in sixty-nine type B thymoma tissues (including B1, B2 and B3) by tissue array analysis with immunohistochemistry staining. The relationship of their expression with clinicopathological parameters, such as tumor stage or WHO classification, was estimated by Spearman's Rank Correlation Test. RESULTS: Sixteen differentially expressed proteins between type B1 and B2 thymoma tissues were identified. The differential levels of ezrin and glutathione S-transferase pi (GSTP1) were validated using immunohistochemistry staining. A statistically significant difference was observed in the positive rate of ezrin expression between type B1 thymoma and type B3 thymoma (Z = -2.963, P < 0.01). Ezrin showed a tendency to be expressed in higher classification tumors from type B1 to B3. A statistical analysis demonstrated that type B2 and B3 tumors had significantly higher positive expression of GSTP1 than the B1 group (type B2 vs. B1: Z = -2.582, P = 0.01; type B3 vs. B1: Z = -4.012, P ≤ 0.001). The results also showed a strong correlation between GSTP1 and WHO type staging of B1 to B3 tumors (Spearman's correlation coefficient: 0.633, P ≤ 0.001). Statistical analysis showed that there was close correlation between GSTP1 and ezrin expression with the clinical stage (Spearman's correlation coefficients, ezrin: 0.481, P < 0.05; GSTP1: 0.484, P < 0.01). CONCLUSIONS: Differentially expressed proteins between type B1 and B2 thymoma tissues were analyzed by comparative proteomic analysis. The techniques of proteomic analysis and tissue array provide a potential tool for screening of key molecules in type B thymoma histological sub-classifications. The statistical analysis of ezrin and GSTP1 expression by immunohistochemistry, especially GSTP1, may be a useful approach for type B thymoma classification.

Comparative proteomic analysis of paclitaxel sensitive A549 lung adenocarcinoma cell line and its resistant counterpart A549-Taxol.

PURPOSE: Paclitaxel is used as the first-line chemotherapy for Non-Small Cell Lung Cancer (NSCLC), but acquired resistance becomes a critical problem. Several mechanisms have been proposed in paclitaxel resistance, but they are not sufficient to exhaustively explain this resistance emergence. To better investigate molecular resistance mechanisms, a comparative proteomic approach was carried out to identify differentially expressed proteins between human lung adenocarcinoma A549 cell line (paclitaxel sensitive) and A549-Taxol cell line (acquired resistant). METHODS: A paclitaxel-resistant subline (A549-Taxol) derived from the parental-sensitive cell line A549 was established by stepwise selection by paclitaxel. Total proteins in the two cell lines were separated by fluorescent differential gel electrophoresis (DIGE). Image analysis was carried out with the DeCyder 2D 6.5 software. Proteins associated with chemoresistance process were identified by matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF-MS/MS). Some key molecules were valuated by Western blot. RESULTS: Thirty proteins were identified and grouped into eight main functional classes according to the biological processes in which they are likely to participate, i.e. signal transduction, cytoskeleton, redox reaction, energy and metabolism, and so on. Alterations of these processes might be involved in paclitaxel resistance. Most of the proteins showed mitochondrial and cytoplasm location. The up-regulation of CK8, CK18, ALDH1, CAST and ANX I in A549-Taxol cell line was verified by Western blot, in coincidence with the data obtained from proteomic analysis. CONCLUSION: For the first time, differentially expressed proteins between paclitaxel-sensitive cell line and paclitaxel-resistant one were explored by comparative proteomic approach in human lung adenocarcinoma. It may be useful for further studying of resistance mechanisms and screening of resistance biomarkers, so as to develop tailored therapeutic strategies.

[Clinical value of CEA and CYFRA21-1 as an assessment indicator of therapeutic efficacy in advanced non-small cell lung cancer patients].

OBJECTIVE: To investigate the value of carcinoembryonic antigen (CEA) or cytokeratin 19 fragment (CYFRA21-1) as an assessment indicator of therapeutic efficacy in advanced non-small cell lung cancer (NSCLC) patients. METHODS: 228 cases of advanced NSCLC with chemotherapy were enrolled into this retrospective study. The serum CEA or CYFRA21-1 levels of all patients were above the cut-off limit before treatment. The relationship between changes of tumor markers (TMs) and imaging therapeutic efficacy or progression-free survival (PFS) was analyzed, and the value of TMs in therapeutic efficacy assessment was evaluated. RESULTS: According to RECIST criteria, partial response (PR) occurred in 40 cases, stable disease (SD) in 151 and PD (progressive disease) in 37. The cut-off values of the changes of TMs between pre- and post-treatment were determined according to the above mentioned criteria. The CEA down (D), stable (S), above (A) groups were 90, 49 and 66 cases, respectively. CYFRA21-1 down (D), stable (S), above (A) groups were 84, 26 and 37 cases, respectively. PR groups were 68.4% and 88.9% in CEA and cyfra21-1 down groups, respectively, 7.9% and 5.6% in the above groups, respectively. PD groups were 59.4% and 76.2% in CEA and CYFRA21-1 above groups, respectively. No PD cases were in the down groups. The changes of TMs in SD group were between them. Statistically significant correlations were observed between changes of TMs and imaging therapeutic efficacy (r(CEA) = 0.45, P = 0.00; r(CYFRA21-1) = 0.44, P = 0.00). PFS among different TMs groups were significantly different (all P < 0.05), which can be used to further distinguish the prognosis among SD subgroups. CONCLUSION: Changes of TMs can be used to predict the imaging therapeutic effect and PFS of the patients, and if the SD group is divided into subgroups according to different therapeutic efficacy and prognosis, it may help the patients to receive individualized treatment.

Analysing protein-protein interaction networks of human liver cancer cell lines with diverse metastasis potential.

PURPOSE: Human hepatocellular carcinoma (HCC) is one of the most mortal tumor. In a previous study, we had constructed glycoprotein expression profiles and glycoprotein databases of three human liver cancer cell lines with diverse metastasis potential. In order to discover vital glycoproteins related to pathogenesis and metastasis of HCC, in this study we analyzed previous data with bioinformatic approach. METHODS: We took previous data to draw the protein-protein interaction (PPI) networks of liver cell lines by searching IntACT database and then using Pajeck software. Further more, we compared the differences between the three PPI networks by drawing the PPI networks of differential glycoproteins and by naming differential display PPI networks. RESULTS: Large numbers of proliferation and apoptosis-relative proteins interact with the differential glycoproteins, and among the differential glycoproteins there are many interactions. CONCLUSIONS: We conclude that neither single nor several proteins cause malignant proliferation of liver cells. "Molecule groups" concept should be introduced into diagnosis and metastasis prediction of the HCC.