We analyzed the amino acid residues present in the water-soluble and transmembrane proteins of 6 thermophilic and 6 mesophilic species of the domains Archaea and Eubacteria, and characterized them as favorable or unfa...We analyzed the amino acid residues present in the water-soluble and transmembrane proteins of 6 thermophilic and 6 mesophilic species of the domains Archaea and Eubacteria, and characterized them as favorable or unfavorable. The characterization was performed by comparing the observed number of each amino acid residue to the expected number calculated from the percentage of nucleotides present in each gene. Amino acids that were more or less abundant than expected were considered as favorable or unfavorable, respectively. Comparisons of amino acid compositions indicated that the water-soluble proteins were rich in charged residues such as Glu, Asp, Lys, and His, whereas hydrophobic residues such as Trp, Phe, and Leu were abundant in transmembrane proteins. Interestingly, our results found that although the Trp residue was abundant in transmembrane proteins, it was not defined as favorable by our calculations, indicating that increased numbers of a particular amino acid does not necessary indicate it is a favorable residue. Amino acids with high G + C content such as Ala, Gly, and Pro were frequently observed as favorable in species with low G + C content. Comparatively, amino acids with low G + C content such as Phe, Tyr, Lys, Ile, and Met were frequently observed as favorable in species with high G + C content. These are the examples to increase the supply of amino acids than expected. Amino acids with neutral G + C content, i.e., Glu and Asp were favorable in water-soluble proteins from all species analyzed, and Cys was unfavorable both in water-soluble and transmembrane proteins. These results indicate that amino acid compositions are essentially determined by the nucleotide sequence of the genes, and the amino acid content is altered by a deviation from expectation.展开更多
BACKGROUND The molecular mechanisms of colorectal cancer development and progression are far from being elucidated.AIM To investigate the role of microRNA-363-3p(miR-363-3p)in the progression of colorectal cancer.METH...BACKGROUND The molecular mechanisms of colorectal cancer development and progression are far from being elucidated.AIM To investigate the role of microRNA-363-3p(miR-363-3p)in the progression of colorectal cancer.METHODS Real-time polymerase chain reaction was performed to detect miRNA expression in human colorectal cancer tissues and paired normal colorectal tissues.PITA 6 was utilized to predict the targets of miR-363-3p.Dual-luciferase reporter system was used to validate the target of miR-363-3p.Plate colony formation assay and wound-healing assay were performed to evaluate cancer cells’clonogenic survival ability and migration ability,respectively.Cell proliferation was examined by cell counting kit-8 assay.Immunohistochemical staining was used to determine the expression level of interferon-induced transmembrane protein 1(IFITM1)in colorectal cancer tissues and adjacent tissues.The TCGA and GTEx databases were used to compare the expression levels of IFITM1 mRNA in colorectal cancer tissues and normal colorectal tissues and analyze the correlation between the expression levels of IFITM1 mRNA and overall survival and disease-free survival of patients.A colorectal cancer cell line with a deficiency of IFITM1 was constructed,and the regulation effect of IFITM1 on the clonogenic growth of colorectal cancer cells was clarified.RESULTS MiR-363-3p was decreased in colorectal cancer tissues compared to normal colorectal tissues.IFITM1 was characterized as a direct target of miR-363-3p.Overexpression of miR-363-3p led to decreased clonogenic survival,proliferation,and migration of colorectal cancer cells,which could be reversed by forced IFITM1 expression.CONCLUSION MiR-363-3p can constrain clonogenic survival,proliferation,and migration of colorectal cancer cells via targeting IFITM1.展开更多
Tmnsmembrane(TM) protein plays an important role in the life activity of the cells, and the prediction of transmembrane helical segments (TMHs) is an important subject in the bioinformatics research. Thus far, sev...Tmnsmembrane(TM) protein plays an important role in the life activity of the cells, and the prediction of transmembrane helical segments (TMHs) is an important subject in the bioinformatics research. Thus far, several prediction methods have been reported, but there are some deficiencies in prediction accuracy and adaptability in these methods. In this paper, a method based on discrete wavelet transform (DWT) was developed to predict the TMHs. Two sets of test data sets containing total 60 protein sequences were utilized to access the effect of the method. Compared with the prediction results of TMHMM2.0 and MEMSAT, the obtained results indicate that the presented method has high prediction accuracy.展开更多
Age-related NADH oxidase (arNOX = ENOX3) proteins are superoxide-generating cell surface oxidases that increase in activity with age beginning at about 30 y. A soluble and truncated exfoliated form of the activity is ...Age-related NADH oxidase (arNOX = ENOX3) proteins are superoxide-generating cell surface oxidases that increase in activity with age beginning at about 30 y. A soluble and truncated exfoliated form of the activity is present in blood and other body fluids. The activity was purified to apparent homogeneity from human urine and resolved by 2-D gel electrophoresis into a series of 24 to 32 kDa components of low isoelectric point. The purified proteins were resistant both to N-terminal sequencing and trypsin cleavage. Cleavage with pepsin revealed peptides corresponding to the TM9 family of transmembrane proteins. Peptide antisera raised to all five members of the human TM9 family sequentially blocked the arNOX activity of human saliva and sera. The soluble truncated N-terminus of the human homolog TM9SF4 was expressed in bacteria. The recombinant protein was characterized biochemically and exhibited ar-NOX activity. The findings identify five arNOX isoforms each of which correspond to one of the five known TM9 family members. The exfoliated soluble arNOX forms are derived from the 24 to 32 kDa N-termini exposed to the cell’s exterior at the cell surface. Each of the shed forms contain putative functional motifs characteristic of ECTO-NOX (ENOX) proteins despite only minimal sequence identity. Our findings identify arNOX as having functional characteristics of ENOX proteins and the TM9 superfamily of proteins as the genetic origins of the five known arNOX isoforms present in human sera, plasma and other body fluids1.展开更多
The hydrophobic effect is the major factor that drives a protein molecule towards folding and to a great degree the stability of protein structures. Therefore the knowledge of hydrophobic regions and its prediction is...The hydrophobic effect is the major factor that drives a protein molecule towards folding and to a great degree the stability of protein structures. Therefore the knowledge of hydrophobic regions and its prediction is of great help in understanding the structure and function of the protein. Hence determination of membrane buried region is a computationally intensive task in bioinformatics. Several prediction methods have been reported but there are some deficiencies in prediction accuracy and adaptability of these methods. Of these proteins that are found embedded in cellular membranes, called as membrane proteins, are of particular importance because they form targets for over 60% of drugs on the market. 20-30% of all the proteins in any organism are membrane proteins. Thus transmembrane protein plays important role in the life activity of the cells. Hence prediction of membrane buried segments in transmembrane proteins is of particular importance. In this paper we have proposed signal processing algorithms based on digital filter for prediction of hydrophobic regions in the transmembrane proteins and found improved prediction efficiency than the existing methods. Hydrophobic regions are extracted by assigning physico-chemical parameter such as hydrophobicity and hydration energy index to each amino acid residue and the resulting numerical representation of the protein is subjected to digital low pass filter. The proposed method is validated on transmembrane proteins using Orientation of Proteins in Membranes (OPM) dataset with various prediction measures and found better prediction accuracy than the existing methods.展开更多
Objective: Lysosome associated protein transmembrane 4 beta (LAPTM4B) was originally identified as a gene in human hepatocellular carcinoma (HCC). It was successfully cloned by fluorescence differential display, ...Objective: Lysosome associated protein transmembrane 4 beta (LAPTM4B) was originally identified as a gene in human hepatocellular carcinoma (HCC). It was successfully cloned by fluorescence differential display, rapid amplification of cDNA ends (RACE) and reverse transcription polymerase chain reaction (RT-PCR). Previous study showed that the novel gene played an important role in the occurrence, development, migration and prognosis of tumors. Pancreatic cancer is an aggressive malignancy with the majority of patients dying within one year after diagnosis. This study tries to find out the relationship between lysosome associated protein transmembrane 4 beta gene polymorphism and the susceptibility of pancreatic cancer. Methods: A case-control study was conducted in China, including 58 pancreatic cancer cases and 156 healthy controls. Human genomic DNA was used as the template, polymerase chain reaction (PCR) was used to detect the distribution of LAPTM4B genotype. Analyses Odds ratio (OR) and corresponding 95% confidence interval (95%CI) with logistic regression were performed. Results: Two alleles of LAPTM4B generated three kinds of genotypes in population, *1/1, *1/2, and *2/2. The genotype frequency of *1/1, *1/2 and *2/2 in the pancreatic cancer group were 41.4%, 44.8% and 13.8% respectively, which were not significantly different from those of healthy group (47.4%, 42.9%, 9.6%) (P=0.773, P=0.291). Also the *2 allele frequency of LAPTM4B among pancreatic cancer had no significantly difference with the controls (P=0.354). When compared to the *1 allele, the people with *2 allele had no increased risk of pancreatic cancer. Conclusion: The gene polymorphism of LAPTM4B may not influence the susceptibility of pancreatic cancer.展开更多
Objective: To clone and analyze the structure of a novel gene, named EST 1 (endoplasmic reticulum localized seven span transmembrane protein 1) and to analyze the expression pattern and intracellular location of EST 1...Objective: To clone and analyze the structure of a novel gene, named EST 1 (endoplasmic reticulum localized seven span transmembrane protein 1) and to analyze the expression pattern and intracellular location of EST 1. Methods: The cDNA library was screened to isolate novel cDNA fragment. The structure of novel gene was analysed by computer software. Expression of EST 1 was analyzed by dot blot and Northern blotting. Intracellular localization was observed after EST 1 enhanced green fluorescence protein (EGFP) fusion gene was transfected into mammalian cells. Results: The full length cDNA of mouse EST 1 was 1 802 bp, with a 1 293 bp open reading frame encoding 431 amino acids. It was predicated that protein encoded by EST 1 contained a signal peptide sequence at the N terminus, seven putative transmembrane domains, and an ER retaining signal at the C terminus. EST 1 EGFP fusion protein showed an ER like intracellular distribution in mammalian cells. Expression pattern analysis showed that EST 1 is expressed in all tissues examined. Conclusion: EST 1 is encoding a putative seven span transmembrane protein localized in endoplasmic reticulum. EST 1 was expressed in all tissues examined, suggesting an essential function of EST 1 in cells.展开更多
Cystic fibrosis transmembrane conductance regulator(CFTR), a glycoprotein with 1480 amino acids, has been well established as a chloride channel mainly expressed in the epithelial cells of various tissues and organs s...Cystic fibrosis transmembrane conductance regulator(CFTR), a glycoprotein with 1480 amino acids, has been well established as a chloride channel mainly expressed in the epithelial cells of various tissues and organs such as lungs, sweat glands, gastrointestinal system, and reproductive organs. Although defective CFTR leads to cystic fibrosis, a common genetic disorder in the Caucasian population, there is accumulating evidence that suggests a novel role of CFTR in various cancers, especially in gastroenterological cancers, such as pancreatic cancer and colon cancer. In this review, we summarize the emerging findings that link CFTR with various cancers, with focus on the association between CFTR defects and gastrointestinal cancers as well as the underlying mechanisms. Further study of CFTR in cancer biology may help pave a new way for the diagnosis and treatment of gastrointestinal cancers.展开更多
Transmembrane proteins are some special and important proteins in cells. Because of their importance and specificity, the prediction of the transmembrane regions has very important theoretical and practical significan...Transmembrane proteins are some special and important proteins in cells. Because of their importance and specificity, the prediction of the transmembrane regions has very important theoretical and practical significance. At present, the prediction methods are mainly based on the physicochemical property and statistic analysis of amino acids. However, these methods are suitable for some environments but inapplicable for other environments. In this paper, the multi-sources information fusion theory has been introduced to predict the transmembrane regions. The proposed method is test on a data set of transmembrane proteins. The results show that the proposed method has the ability of predicting the transmembrane regions as a good performance and powerful tool.展开更多
Colorectal cancer (CRC) is an important health issue in Taiwan. There were over ten thousand newly diagnosed CRC patients each year. The outcome of late stage CRC still remains to be improved, and tumor markers are ex...Colorectal cancer (CRC) is an important health issue in Taiwan. There were over ten thousand newly diagnosed CRC patients each year. The outcome of late stage CRC still remains to be improved, and tumor markers are expected to improve CRC detection and management. From a colorectal cancer cell secretome database, we chose four proteins as candidates for clinical verification, including tumor-associated calcium signal transducer 2 (TROP2, TACSTD2), transmembrane 9 superfamily member 2 (TM9SF2), and tetraspanin-6 (TSPAN6), and tumor necrosis factor receptor superfamily member 16 (NGFR). Different groups of 30 CRC patients’ tissue samples collected from Chang Gung Memorial Hospital were analyzed by immunohistochemistry (IHC) for the four proteins, and the results were scored by pathologist. For all the four candidate proteins, marked differences of IHC score existed between tumor and adjacent non-tumor counterpart. However, there were only trends between higher protein expression levels and worse outcome. Three proteins (TROP2, TM9SF2 and NGFR) had trends between higher tissue expression and tumor stage or lymph node metastasis. Our study revealed that tissue expression of four proteins (TROP2, TM9SF2, TSPAN6, and NGFR) was markedly different between tumor and adjacent non-tumor counterparts. Overexpression of all these four proteins showed some trends with poorer survival.展开更多
文摘We analyzed the amino acid residues present in the water-soluble and transmembrane proteins of 6 thermophilic and 6 mesophilic species of the domains Archaea and Eubacteria, and characterized them as favorable or unfavorable. The characterization was performed by comparing the observed number of each amino acid residue to the expected number calculated from the percentage of nucleotides present in each gene. Amino acids that were more or less abundant than expected were considered as favorable or unfavorable, respectively. Comparisons of amino acid compositions indicated that the water-soluble proteins were rich in charged residues such as Glu, Asp, Lys, and His, whereas hydrophobic residues such as Trp, Phe, and Leu were abundant in transmembrane proteins. Interestingly, our results found that although the Trp residue was abundant in transmembrane proteins, it was not defined as favorable by our calculations, indicating that increased numbers of a particular amino acid does not necessary indicate it is a favorable residue. Amino acids with high G + C content such as Ala, Gly, and Pro were frequently observed as favorable in species with low G + C content. Comparatively, amino acids with low G + C content such as Phe, Tyr, Lys, Ile, and Met were frequently observed as favorable in species with high G + C content. These are the examples to increase the supply of amino acids than expected. Amino acids with neutral G + C content, i.e., Glu and Asp were favorable in water-soluble proteins from all species analyzed, and Cys was unfavorable both in water-soluble and transmembrane proteins. These results indicate that amino acid compositions are essentially determined by the nucleotide sequence of the genes, and the amino acid content is altered by a deviation from expectation.
文摘BACKGROUND The molecular mechanisms of colorectal cancer development and progression are far from being elucidated.AIM To investigate the role of microRNA-363-3p(miR-363-3p)in the progression of colorectal cancer.METHODS Real-time polymerase chain reaction was performed to detect miRNA expression in human colorectal cancer tissues and paired normal colorectal tissues.PITA 6 was utilized to predict the targets of miR-363-3p.Dual-luciferase reporter system was used to validate the target of miR-363-3p.Plate colony formation assay and wound-healing assay were performed to evaluate cancer cells’clonogenic survival ability and migration ability,respectively.Cell proliferation was examined by cell counting kit-8 assay.Immunohistochemical staining was used to determine the expression level of interferon-induced transmembrane protein 1(IFITM1)in colorectal cancer tissues and adjacent tissues.The TCGA and GTEx databases were used to compare the expression levels of IFITM1 mRNA in colorectal cancer tissues and normal colorectal tissues and analyze the correlation between the expression levels of IFITM1 mRNA and overall survival and disease-free survival of patients.A colorectal cancer cell line with a deficiency of IFITM1 was constructed,and the regulation effect of IFITM1 on the clonogenic growth of colorectal cancer cells was clarified.RESULTS MiR-363-3p was decreased in colorectal cancer tissues compared to normal colorectal tissues.IFITM1 was characterized as a direct target of miR-363-3p.Overexpression of miR-363-3p led to decreased clonogenic survival,proliferation,and migration of colorectal cancer cells,which could be reversed by forced IFITM1 expression.CONCLUSION MiR-363-3p can constrain clonogenic survival,proliferation,and migration of colorectal cancer cells via targeting IFITM1.
基金Project supported by National High-Technology Research andDevelopment Program of China (Grant No .2002AA234021)
文摘Tmnsmembrane(TM) protein plays an important role in the life activity of the cells, and the prediction of transmembrane helical segments (TMHs) is an important subject in the bioinformatics research. Thus far, several prediction methods have been reported, but there are some deficiencies in prediction accuracy and adaptability in these methods. In this paper, a method based on discrete wavelet transform (DWT) was developed to predict the TMHs. Two sets of test data sets containing total 60 protein sequences were utilized to access the effect of the method. Compared with the prediction results of TMHMM2.0 and MEMSAT, the obtained results indicate that the presented method has high prediction accuracy.
文摘Age-related NADH oxidase (arNOX = ENOX3) proteins are superoxide-generating cell surface oxidases that increase in activity with age beginning at about 30 y. A soluble and truncated exfoliated form of the activity is present in blood and other body fluids. The activity was purified to apparent homogeneity from human urine and resolved by 2-D gel electrophoresis into a series of 24 to 32 kDa components of low isoelectric point. The purified proteins were resistant both to N-terminal sequencing and trypsin cleavage. Cleavage with pepsin revealed peptides corresponding to the TM9 family of transmembrane proteins. Peptide antisera raised to all five members of the human TM9 family sequentially blocked the arNOX activity of human saliva and sera. The soluble truncated N-terminus of the human homolog TM9SF4 was expressed in bacteria. The recombinant protein was characterized biochemically and exhibited ar-NOX activity. The findings identify five arNOX isoforms each of which correspond to one of the five known TM9 family members. The exfoliated soluble arNOX forms are derived from the 24 to 32 kDa N-termini exposed to the cell’s exterior at the cell surface. Each of the shed forms contain putative functional motifs characteristic of ECTO-NOX (ENOX) proteins despite only minimal sequence identity. Our findings identify arNOX as having functional characteristics of ENOX proteins and the TM9 superfamily of proteins as the genetic origins of the five known arNOX isoforms present in human sera, plasma and other body fluids1.
文摘The hydrophobic effect is the major factor that drives a protein molecule towards folding and to a great degree the stability of protein structures. Therefore the knowledge of hydrophobic regions and its prediction is of great help in understanding the structure and function of the protein. Hence determination of membrane buried region is a computationally intensive task in bioinformatics. Several prediction methods have been reported but there are some deficiencies in prediction accuracy and adaptability of these methods. Of these proteins that are found embedded in cellular membranes, called as membrane proteins, are of particular importance because they form targets for over 60% of drugs on the market. 20-30% of all the proteins in any organism are membrane proteins. Thus transmembrane protein plays important role in the life activity of the cells. Hence prediction of membrane buried segments in transmembrane proteins is of particular importance. In this paper we have proposed signal processing algorithms based on digital filter for prediction of hydrophobic regions in the transmembrane proteins and found improved prediction efficiency than the existing methods. Hydrophobic regions are extracted by assigning physico-chemical parameter such as hydrophobicity and hydration energy index to each amino acid residue and the resulting numerical representation of the protein is subjected to digital low pass filter. The proposed method is validated on transmembrane proteins using Orientation of Proteins in Membranes (OPM) dataset with various prediction measures and found better prediction accuracy than the existing methods.
基金supported by the National Natural Science Foundation of China(No. 81071422)
文摘Objective: Lysosome associated protein transmembrane 4 beta (LAPTM4B) was originally identified as a gene in human hepatocellular carcinoma (HCC). It was successfully cloned by fluorescence differential display, rapid amplification of cDNA ends (RACE) and reverse transcription polymerase chain reaction (RT-PCR). Previous study showed that the novel gene played an important role in the occurrence, development, migration and prognosis of tumors. Pancreatic cancer is an aggressive malignancy with the majority of patients dying within one year after diagnosis. This study tries to find out the relationship between lysosome associated protein transmembrane 4 beta gene polymorphism and the susceptibility of pancreatic cancer. Methods: A case-control study was conducted in China, including 58 pancreatic cancer cases and 156 healthy controls. Human genomic DNA was used as the template, polymerase chain reaction (PCR) was used to detect the distribution of LAPTM4B genotype. Analyses Odds ratio (OR) and corresponding 95% confidence interval (95%CI) with logistic regression were performed. Results: Two alleles of LAPTM4B generated three kinds of genotypes in population, *1/1, *1/2, and *2/2. The genotype frequency of *1/1, *1/2 and *2/2 in the pancreatic cancer group were 41.4%, 44.8% and 13.8% respectively, which were not significantly different from those of healthy group (47.4%, 42.9%, 9.6%) (P=0.773, P=0.291). Also the *2 allele frequency of LAPTM4B among pancreatic cancer had no significantly difference with the controls (P=0.354). When compared to the *1 allele, the people with *2 allele had no increased risk of pancreatic cancer. Conclusion: The gene polymorphism of LAPTM4B may not influence the susceptibility of pancreatic cancer.
基金SupportedbytheNationalNaturalScienceFoundation (No .39970 376) andtheMinistryofScienceandTechnologyofChina (No .2 0 0 1CB50 990 6)
文摘Objective: To clone and analyze the structure of a novel gene, named EST 1 (endoplasmic reticulum localized seven span transmembrane protein 1) and to analyze the expression pattern and intracellular location of EST 1. Methods: The cDNA library was screened to isolate novel cDNA fragment. The structure of novel gene was analysed by computer software. Expression of EST 1 was analyzed by dot blot and Northern blotting. Intracellular localization was observed after EST 1 enhanced green fluorescence protein (EGFP) fusion gene was transfected into mammalian cells. Results: The full length cDNA of mouse EST 1 was 1 802 bp, with a 1 293 bp open reading frame encoding 431 amino acids. It was predicated that protein encoded by EST 1 contained a signal peptide sequence at the N terminus, seven putative transmembrane domains, and an ER retaining signal at the C terminus. EST 1 EGFP fusion protein showed an ER like intracellular distribution in mammalian cells. Expression pattern analysis showed that EST 1 is expressed in all tissues examined. Conclusion: EST 1 is encoding a putative seven span transmembrane protein localized in endoplasmic reticulum. EST 1 was expressed in all tissues examined, suggesting an essential function of EST 1 in cells.
基金Supported by American Cancer Society Institutional Research to Li C,No.11-053-01-IRGNational Institutes of Health grant HL128647
文摘Cystic fibrosis transmembrane conductance regulator(CFTR), a glycoprotein with 1480 amino acids, has been well established as a chloride channel mainly expressed in the epithelial cells of various tissues and organs such as lungs, sweat glands, gastrointestinal system, and reproductive organs. Although defective CFTR leads to cystic fibrosis, a common genetic disorder in the Caucasian population, there is accumulating evidence that suggests a novel role of CFTR in various cancers, especially in gastroenterological cancers, such as pancreatic cancer and colon cancer. In this review, we summarize the emerging findings that link CFTR with various cancers, with focus on the association between CFTR defects and gastrointestinal cancers as well as the underlying mechanisms. Further study of CFTR in cancer biology may help pave a new way for the diagnosis and treatment of gastrointestinal cancers.
基金Supported by the National Natural Science Foundation of China (No. 60874105, 61174022)the Program for New Century Excellent Talents in University (No. NCET-08-0345)the Chongqing Natural Science Foundation (No. CSCT, 2010BA2003)
文摘Transmembrane proteins are some special and important proteins in cells. Because of their importance and specificity, the prediction of the transmembrane regions has very important theoretical and practical significance. At present, the prediction methods are mainly based on the physicochemical property and statistic analysis of amino acids. However, these methods are suitable for some environments but inapplicable for other environments. In this paper, the multi-sources information fusion theory has been introduced to predict the transmembrane regions. The proposed method is test on a data set of transmembrane proteins. The results show that the proposed method has the ability of predicting the transmembrane regions as a good performance and powerful tool.
文摘Colorectal cancer (CRC) is an important health issue in Taiwan. There were over ten thousand newly diagnosed CRC patients each year. The outcome of late stage CRC still remains to be improved, and tumor markers are expected to improve CRC detection and management. From a colorectal cancer cell secretome database, we chose four proteins as candidates for clinical verification, including tumor-associated calcium signal transducer 2 (TROP2, TACSTD2), transmembrane 9 superfamily member 2 (TM9SF2), and tetraspanin-6 (TSPAN6), and tumor necrosis factor receptor superfamily member 16 (NGFR). Different groups of 30 CRC patients’ tissue samples collected from Chang Gung Memorial Hospital were analyzed by immunohistochemistry (IHC) for the four proteins, and the results were scored by pathologist. For all the four candidate proteins, marked differences of IHC score existed between tumor and adjacent non-tumor counterpart. However, there were only trends between higher protein expression levels and worse outcome. Three proteins (TROP2, TM9SF2 and NGFR) had trends between higher tissue expression and tumor stage or lymph node metastasis. Our study revealed that tissue expression of four proteins (TROP2, TM9SF2, TSPAN6, and NGFR) was markedly different between tumor and adjacent non-tumor counterparts. Overexpression of all these four proteins showed some trends with poorer survival.