The relationship between Lamin B2 and tumor proliferation and migration is unclear. We explored the impact of Lamin B2 on non-small cell lung cancer (NSCLC) cells. Tissue microarray and immunohistochemistry were combined to evaluate Lamin B2 expression and its relationship with the clinicopathological factors found in NSCLC. Western blotting, immunofluorescence analysis, and bioinformatics were used to investigate the effects of Lamin B2 on various regulatory pathways in cancer. Cytological experiments were conducted to evaluate Lamin B2 expression in tumor cells. We conducted co-immunoprecipitation and chromatin immunoprecipitation to explore the molecular mechanisms underlying the relationship between Lamin B2 and NSCLC and evaluate the results of rescue experiments. Lamin B2 was highly expressed in NSCLC and positively correlated with lymph node metastasis. In NSCLC, Lamin B2 interacted with Cyclin D1, upregulating G9α expression, thus increasing H3K9me2 levels. H3K9me2 binds to the promoter region of the E-cadherin gene (CDH1) to induce CDH1 silencing and promotes cancer cell migration. Thus, we found that Lamin B2 was highly expressed in NSCLC cells and promoted their migration by increasing H3K9me2 levels, which induced E-cadherin gene silencing.

[This corrects the article DOI: 10.2147/OTT.S263815.].

In lung cancer, it has been widely accepted that invasive carcinomas are derived from precursor and/or preinvasive lesions, such as squamous metaplasia and dysplasia are part of a continuum of histological changes before carcinoma in situ and squamous cell carcinoma (SCC) [ [1] Denisov E.V. et al. Premalignant lesions of squamous cell carcinoma of the lung: the molecular make-up and factors affecting their progression. Lung Cancer. 2019; 135: 21-28 Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar ]. Similarly, atypical adenomatous hyperplasia and adenocarcinoma (ADC) in situ may evolve to invasive ADC [ [2] Xu X. et al. Targeted next-generation sequencing for analyzing the genetic alterations in atypical adenomatous hyperplasia and adenocarcinoma in situ. J. Cancer Res. Clin. Oncol. 2017; 143: 2447-2453 Crossref PubMed Scopus (12) Google Scholar ]. Diffuse pulmonary neuroendocrine cell hyperplasia and tumourlets are precursor lesions of carcinoid [ [3] Koo C.W. et al. Spectrum of pulmonary neuroendocrine cell proliferation: diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, tumorlet, and carcinoids. AJR Am. J. Roentgenol. 2010; 195: 661-668 Crossref PubMed Scopus (34) Google Scholar ]. However, few studies have revealed whether large cell carcinoma (LCC) has precursor or preinvasive lesions. Therefore, it is generally considered that LCC has no preinvasive lesions [ [4] Travis W.D. Müller-Hermelink H.K. Harris C.C. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart IARC WHO Classification of Tumours. IARC Press, Lyon2004 Google Scholar ]. Herein, we report the pathological observation of two cases of LCC in the early stage, which may shed new light on this question. Case 1: A 65-year-old male presented a mass in the basal segment of the right lower lobe of the lung revealed by CT during the physical examination. The mass was closely related to the bronchi (Fig. 1A). After excluding extrapulmonary metastases by imageology, a surgery was performed and the tumor was grayish-yellow, hard, and brittle. Microscopically, large polygonal cancer cells were arranged in nests, with prominent nucleoli, abundant mitotic figures, and necrosis. A region of carcinoma in situ (Fig. 1B), 2.05 mm in diameter, was found in the bronchial mucosa adjacent to the invasive lesions, and these two parts shared the same cellular morphology (Fig. 1C-D) and immunoprofiles (Fig. 1E-L). CK5/6, p63, p40, TTF-1, napsin-A, CD56, synaptophysin, chromograninA, MUC-1, and PAS-AB staining were all negative, and only CK staining was positive, with Ki-67 index about 40 %. A transition zone from normal bronchial epithelium to large cell carcinoma region could be observed (Fig. 1D). In the transition zone, some large cells with obvious atypia can be observed, with positive staining of CK and negative staining for other markers. The diagnosis of LCC with null immunohistochemical features (LCC-null) was rendered. There was no metastasis in lymph nodes. The patient is free from recurrence 84 months after the initial diagnosis. Case 2: A 47-year-old male presented with hemoptysis and chest pain for 10 days. On the CT scan, a mass was found in the apico-posterior segment of the upper lobe of the left lung (Fig. 2A). Extrapulmonary metastases were excluded, and a gray-pink mass with a diameter of 1 cm was identified within the bronchus during the lobectomy (Fig. 2B). Microscopically, the tumor cells were in solid and papillary patterns, invading the bronchial wall (Fig. 2C). The lesion was adjacent to normal bronchial mucosa (Fig. 2D). The carcinoma cells were large and polygonal, with prominent nucleoli and high-frequent mitosis (Fig. 2E). Immunohistochemistry staining showed the same results as in case 1, supporting the diagnosis of LCC-null (Fig. 2F-H). No metastasis was found in lymph nodes. The patient is free from recurrence 38 months after the initial diagnosis.

Shuli Liu Jinping Wang Xue Luo Xiaoman Li Yuan Miao 1 Liang Wang 1 Qingchang Li Xueshan Qiu En-Hua Wang 1Department of Pathology, College of Basic Medical Sciences and the First Affiliated Hospital, China Medical University, Shenyang, People’s Republic of China; 2Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, People’s Republic of China Abstract: Low-grade fetal lung adenocarcinoma (L-FLAC) is an exceptionally rare pulmonary tumor, presenting with unclear histological and molecular features. In particular, the potential driver genes of L-FLAC remain elusive. To date, only five reports have documented genetic aberrations in L-FLAC. In the current study, we describe an unusual case of L-FLAC coexisting with adenocarcinoma in situ (AIS) of the lung, harboring different genetic mutations. A 39-year-old non-smoker female patient was referred to our hospital with the chief complaint of dyspnea for 20 days. Chest computed tomography (CT) revealed a 2.5×1.5×1.5 cm nodule in the right middle lobe, with no mediastinal lymph node enlargement or distant metastases. Thoracoscopic surgery was performed to remove the nodules. Histopathological analysis of the tissue sections, based on findings from immunohistochemical staining, confirmed a diagnosis of L-FLAC coexisting with AIS of the lung. Nextgeneration sequencing revealed L-FLAC-based mutations in DICER1 and CTNNB1, and AIS harboring KRAS mutations. Currently, the patient remains recurrence-free 17 months after the initial diagnosis. This report presents the first case demonstrating the coexistence of L-FLAC and AIS in the same pulmonary nodule, harboring different genetic mutations. Based on the literature review, this is the second reported case of L-FLAC bearing DICER1 mutations.

BACKGROUND:WW and C2 domain-containing protein-3 (WWC3) was identified in our previous studies as a tumor suppressor gene, which inhibits the proliferation and invasiveness of lung cancer cells. However, the relationship between WWC3 and autophagy and apoptosis in lung cancer cells is unclear. In this study, we aimed to investigate the potential role of WWC3 in starvation-induced autophagy and apoptosis in non-small cell lung carcinoma (NSCLC) cells.METHODS:The immunoblotting assay and quantitative real-time polymerase chain reaction (RT-qPCR) were used for observing the change of WWC3 protein and mRNA level under starvation condition. The immunoblotting assay and immunofluorescence assay were performed to detect the impact of WWC3 expression on autophagy process induced by Earle's balanced salt solution (EBSS) in lung cancer cells; APC/propidium iodide (PI) apoptosis assay, caspase-3/7 activity assay and MTT assay were used for the apoptosis and proliferation detection of lung cancer cells.RESULTS:After starvation had been induced with EBSS, WWC3 expression was significantly decreased in the NSCLC cells. Ectopic WWC3 expression weakened the autophagy process in a Beclin1-independent manner and promoted non-small cell lung cancer cell apoptosis via EBSS starvation. Moreover, the inhibition of WWC3 gene knockout was weakened by 3-methyladenine (3-MA), an autophagy inhibitor.CONCLUSIONS:These results indicate that WWC3 promotes apoptosis and death of starved lung cancer cells, at least partly through autophagy.

Abstract Low-grade fetal lung adenocarcinoma (L-FLAC) is an exceptionally rare pulmonary tumor, presenting with unclear histological and molecular features. In particular, the potential driver genes of L-FLAC remain elusive. To date, only five reports have documented genetic aberrations in L-FLAC. In the current study, we describe an unusual case of L-FLAC coexisting with adenocarcinoma in situ (AIS) of the lung, harboring different genetic mutations. A 39-year-old non-smoker female patient was referred to our hospital with the chief complaint of dyspnea for 20 days. Chest computed tomography (CT) revealed a 2.5×1.5×1.5 cm nodule in the right middle lobe, with no mediastinal lymph node enlargement or distant metastases. Thoracoscopic surgery was performed to remove the nodules. Histopathological analysis of the tissue sections, based on findings from immunohistochemical staining, confirmed a diagnosis of L-FLAC coexisting with AIS of the lung. Next-generation sequencing revealed L-FLAC-based mutations in DICER1 and CTNNB1, and AIS harboring KRAS mutations. Currently, the patient remains recurrence-free 17 months after the initial diagnosis. This report presents the first case demonstrating the coexistence of L-FLAC and AIS in the same pulmonary nodule, harboring different genetic mutations. Based on the literature review, this is the second reported case of L-FLAC bearing DICER1 mutations.

RATIONALE:Bronchiolar adenoma (BA) is a newly designated rare entity of the lung, including both the currently designated ciliated muconodular papillary tumor (CMPT) and so-called non-classic CMPT. The most prominent histological feature of BAs is the bilayered cell structures composed of the continuous basal cell layer and the luminal layer which consists of different proportion of mucinous cells, ciliated cells, Clara cells and/or type II pneumocytes. BA purely covered by mucinous cells without other components in the luminal layer has never been reported.PATIENT CONCERNS:An 82-year-old female patient was detected a 0.8 cm ground glass nodule in the left lower lobe of the lung.DIAGNOSES:The serum levels of tumor markers were normal.INTERVENTIONS:The patient underwent a segmentectomy of the left lower lobe.OUTCOMES:The postoperative pathological diagnosis was BA. Molecular analysis revealed that the tumor harbored ALK rearrangement and BRAF mutations simultaneously. There was no recurrence in 17 months of follow-up.LESSONS:BA can be lined only by mucinous cells, without any cuboidal and/or ciliated cells in the surface layer. This sets a dangerous pitfall in differentiation diagnosis with invasive mucinous adenocarcinoma especially during intraoperative frozen pathological diagnosis.

Norepinephrine (NE) can regulate natural killer (NK) cell activity, but the mechanism remains unclear. In the present study the roles of adrenergic receptors (ARs) in inhibiting NK92‑MI cells‑mediated cytotoxicity by NE were investigated. To examine the effect of NE on NK92‑MI cytotoxicity, a lactate dehydrogenase‑release cytotoxicity assay was used to determine the cytotoxicity of NK92‑MI cells against K562 cells. To evaluate the possible function of the α, β1 and β2 AR in mediating NE‑induced effects, NK92‑MI cells were pre‑incubated with phenol‑amine, CGP20712A and ICI118551 prior to stimulation by NE. To evaluate the role of cyclic adenosine monophosphate (cAMP)‑protein kinase A (PKA) signaling pathway in the inhibitory effect on cytotoxicity of NK92‑MI cell by NE, NK92‑MI cells were pre‑incubated with PKA inhibitor Rp‑8‑Br‑cAMP prior to stimulation by NE. It was demonstrated that NE decreased cytotoxicity and downregulated the expression of perforin, granzyme B and interferon (IFN)‑γ of NK92‑MI cells in a dose‑dependent manner. Blocking NE functional receptors by ARs antagonists, particularly of β2 AR antagonist, suppressed the inhibitory effect of NE on cytotoxicity and expression of perforin, granzyme B, IFN‑γ of NK92‑MI cells significantly. Blockade of β2 AR in NE treated NK92‑MI cells resulted in a reduction of the expression of phosphorylated (p)‑cAMP‑responsive element‑binding protein (CREB) and intracellular cAMP concentration. Inhibiting the activity of PKA by Rp‑8‑Br‑cAMP in NE treated NK92‑MI cells resulted in increased cytotoxicity. The results of the present study suggest that NE can inhibit cytotoxicity and expression of perforin, granzyme B, IFN‑γ of NK92‑MI cell mainly via the β2‑AR/cAMP/PKA/p‑CREB signaling pathway.

BACKGROUND/AIMS:The therapeutic efficacy of paclitaxel is hampered by chemotherapeutic resistance in non-small cell lung cancer (NSCLC). Rsf-1 enhanced paclitaxel resistance via nuclear factor-κB (NF-κB) in ovarian cancer cells and nasopharyngeal carcinoma. This study assessed the function of Rsf-1 in the modulation of the sensitivity of NSCLC to paclitaxel via the NF-κB pathway.METHODS:The mRNA and protein levels of the related genes were quantified by RT-PCR and Western blotting. Rsf-1 silencing was achieved with CRISPR/Cas9 gene editing. Cell cycle, migration and proliferation were tested with flow cytometry, transwell test and CCK8 test. Cell apoptosis was analyzed with flow cytometry and quantification of C-capase3. The parameters of the tumors were measured in H460 cell xenograft mice.RESULTS:Rsf-1 was highly expressed in H460 and H1299 cells. Rsf-1 knockout caused cell arrest at the G1 phase, increased cell apoptosis, and decreased migration and cell proliferation. Rsf-1 knockout increased the inhibition of cell proliferation, the reduction in cell migration and the augment in cell apoptosis in paclitaxel treated H460 and H1299 cells. Rsf-1 knockout further enhanced the paclitaxel-mediated decrease in the volume and weight of the tumors in H460 cell xenograft mice. Helenalin and Rsf-1 knockout decreased the protein levels of p-P65, BcL2, CFLAR, and XIAP; hSNF2H knockout decreased the protein level of NF-κB p-P65 without altering Rsf-1 and p65 protein levels, while Rsf-1 and hSNF2H double knockout decreased the level of NF-κB p-P65, in H1299 and H460 cells.CONCLUSION:These results demonstrate that Rsf-1 influences the sensitivity of NSCLC to paclitaxel via regulation of the NF-κB pathway and its downstream genes.

High-risk human papillomavirus (HPV) infection may play an important role in non-small cell lung carcinoma (NSCLC) development. However, some recent studies have proved that it was not directly associated with lung cancer. The aim of this study was to evaluate the underlying molecular mechanism that HPV16 regulate the expression of GLUT1 and may promote the development of lung cancer. HPV16, HIF-1α, and GLUT1 were detected in pleural effusions of patients with lung cancer (n = 95) and with benign lung disease (n = 55) by immunocytochemistry. Western blotting and qRT-PCR were used to detect the expression chances of HPV16 E6/E7, HIF-1α, and GLUT1 in lung cancer cells. HPV16, HIF-1α, and GLUT1 were significantly more likely to be expressed in the malignant group than in the benign group as detected by immunocytochemistry (ICC), and HIF-1α was significantly correlated with HPV16 or GLUT1 in the malignant group (P < 0.01). Expression changes of E6 and E7 significantly promoted the protein expression of HIF-1α, the expression of both protein and mRNA of GLUT1, but had no effect on the expression of HIF-1α mRNA in lung cancer cells. After inhibition of HIF-1α, it obviously downregulated the expression of both protein and mRNA of GLUT1 in lung cancer cells. E6 and E7 regulated the expression of GLUT1 may be due to the mediation of HIF-1α in lung cancer cells. These results suggest that both E6 and E7 play the important role in the regulation of Warburg effect and may be a valuable therapeutic target for HPV-related cancer.

Little is known regarding the expression or clinical significance of δ-catenin, a member of the catenin family, in colorectal cancer (CRC). The present study examined the expression of δ-catenin using immunohistochemistry in 110 cases of CRC, including 70 cases with complete follow‑up records and 40 cases with paired lymph node metastases. In addition, δ‑catenin mRNA and protein expression were compared in 30 pairs of matched CRC and normal colorectal tissues by reverse transcription quantitative polymerase chain reaction and western blot analysis. δ‑Catenin was weakly expressed or absent in the cytoplasm of normal intestinal epithelial cells, whereas positive δ‑catenin expression localized to the cytoplasm was observed in CRC cells. The rate of positive δ‑catenin expression in CRC (68.18%; 75/110) was significantly higher than that in normal colorectal tissues (36.7%; 11/30; P<0.001). In addition, δ‑catenin mRNA and protein expression were significantly increased in CRC tissues compared to those in their matched normal tissues (all P<0.05). The expression of δ‑catenin in stage III‑IV CRC was higher than that in stage I‑II CRC, and the expression of δ‑catenin in the tumors of patients with lymph node metastases was higher than that in patients without lymph node metastases. Kaplan‑Meier survival curves demonstrated that the survival time of patients with positive δ‑catenin expression was shorter than that of patients with negative δ‑catenin expression (P=0.005). Furthermore, Cox multivariate analysis indicated that the tumor, nodes and metastasis stage (P=0.02) and positive δ-catenin expression (P=0.033) were independent prognostic factors in CRC. The present study therefore indicated that δ-catenin may be a suitable independent prognostic factor for CRC.

B c l-2及P53基因可以调控细胞凋亡。我们应用B c l-2及P53基因产物单克隆抗体，标记53例甲状腺腺瘤及41例甲状腺癌。结果发现，甲状腺癌和部分甲状腺腺瘤有B c l-2及P53基因产物表达。阳性产物分别定位于肿瘤细胞浆和细胞核。在甲状腺癌，二种基因产物阳性表达率在恶性度较高的未分化癌和滤泡癌或临床TNM分期I I、IV期的病例增高显著。提示Bcl-2及突变型P53基因产物与甲状腺肿瘤的发生、发展及预后有关。

Delta-catenin, a member of the p120-catenin subfamily, and the Rho GTPase RhoA both have roles in the regulation of the cytoskeleton. In this study, we found that delta-catenin positive expression and RhoA over-expression is consistently found in non-small cell lung cancer, but not in normal lung tissue, and that their co-expression was significantly associated with histological type, differentiation, pTNM stage, lymphatic metastasis and a poor prognosis. We also demonstrate that delta-catenin can directly interact with RhoA and regulate its activity, which in turn mediates tumor invasion and metastasis.

目的 探讨FRMPD2基因表达下调对肺癌细胞生存、增殖以及黏附能力的影响.方法 将FRMPD2shRNA转染肺癌细胞SPC-A-1后,通过免疫荧光染色和Western blot检测FRMPD2的表达,并采用平板克隆形成实验、CCK-8增殖实验和细胞黏附实验测定转染细胞的生物学行为,分析FRMPD2表达相关的生物学效应.结果 免疫荧光染色和Western blot结果均提示FRMPD2 shRNA有效地下调了FRMPD2蛋白表达(P＜0.05).体外实验显示,FRMPD2表达下调后细胞的集落形成率、细胞增殖能力和黏附率明显下降(P＜0.05).结论 FRMPD2在肺癌细胞的生存、增殖和黏附等方面发挥重要作用.

Objective:To discuss T - cadherin exPression in gastric cancer and the relationshiP between VEGF, MVD. Methods:Using immunohistochemical SP method to test the exPression of T - cadherin,vascular endothelial growth factor(VEGF)and CD34 in 80 cases of gastric cancer tissue and normal gastric tissue adjacent to carcinoma. Results:T - cadherin exPressied in the gastric cancer cell membrane,Positive rate was 45. 0%(36 / 80),while in normal gastric tissues adjacent to carcinoma T - cadherin Positive rate was 62. 5%(50 / 80,P = 0. 026). VEGF in normal cells adjacent to carcinoma Positive rate was 28. 75% ,the exPression Positive rate was 71. 25% in cancer of the stomach(P = 0. 000). CD34 Positive cells mark of caPillaries in gastric cancer significantly more than the normal tissue(54. 96 ± 7. 28 / ePF vs 27. 50 ± 6. 10 / ePF,P ﹤ 0. 001). T - cadherin was negatively correlated with VEGF Protein exPression(P ﹤ 0. 001). The MVD value of T - cadherin Positive grouP was obviously lower than negative low exPression grouP(P ﹤ 0. 001). The T - cadherin,VEGF and CD34 in gastric cancer Patients were not correlatad gender,age,size,( P ﹥ 0 . 05 ),but with tissue differentiation degree and lymPh node metastasis and PTNM stage (P ﹤ 0. 05). Conclusion:T - cadherin abnormal exPression can be used for gastric cancer diagnosis,treatment and Prognosis evaluation.

Thyroid cancer 1 (TC-1, C8orf4) is involved in the development of many cancers. In this study, we investigated the correlation between the expression of TC-1 and the clinicopathological characteristics of ovarian and colorectal adenocarcinomas. We also explored the possible use of TC-1 as a marker to distinguish between metastatic tumors of the ovary and colorectum. We used immunohistochemistry to examine the expression level of TC-1 in 100 ovarian and 100 colorectal adenocarcinomas and 25 metastatic carcinomas with the ovary or colorectum as primary site. TC-1 was expressed in all ovarian carcinoma samples. The high expression rate of TC-1 was 84 % in ovarian carcinomas, which was much higher than that observed in colorectal adenocarcinomas (35 %, P < 0.001). High expression of TC-1 significantly correlated with poor differentiation of ovarian carcinomas (P = 0.013). To explore the value of TC-1 in distinguishing metastatic ovarian cancers from colorectal cancers, we found the area under the receiver operator characteristic curve of TC-1 to be 0.819 (95 % confidence interval, 0.760–0.878; P < 0.001). Furthermore, TC-1 was highly expressed in 100 % of nine metastatic ovarian cancers, but only in 31 % of 16 metastatic colorectal cancers. The higher expression of TC-1 in ovarian compared to colorectal adenocarcinomas suggests its potential use as a marker, to distinguish between metastatic ovarian and colorectal adenocarcinomas.

目的 探讨肝激酶B1(LKB1)在肺腺癌中的表达及意义.方法 应用免疫组化方法 检测LKB1在87例肺腺癌及癌旁正常肺组织中的表达,并分析其表达与肿瘤临床病理因素及预后的相关性.结果 LKB1在正常肺组织中高表达,在肺腺癌中表达下调(P<0.001);在肺腺癌中,LKB1表达下调与患者的淋巴结转移正相关(r=0.337,P=0.002)同时与高分化负相关(r=-0.269,P=0.012);在预后分析中,除了TNM分期(P<0.001)之外,LKB1表达下调也是影响肺腺癌患者预后的独立因素(P=0.001).结论 LKB1表达下调促进肺腺癌的发生发展,并与其不良预后相关.

目的:探讨NEDD9在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达及意义.方法:应用免疫组化方法检测NEDD9在145例非小细胞肺癌及癌旁正常肺组织中的表达,并分析其表达与肿瘤临床病理因素及预后的相关性.结果:NEDD9在非小细胞肺癌中高表达,在正常肺组织中低表达(P＜0.001)；在非小细胞肺癌中,NEDD9的高表达与患者的阳性淋巴结转移及高TNM分期正相关(P=0.001和P=0.039)；在预后分析中,NEDD9高表达的患者在单因素和多因素分析中均表现出更差的5年累计生存率(P＜0.001).结论:NEDD9促进非小细胞肺癌的侵袭转移,并与较差的预后相关.

Atonal homolog 1 (Atoh1) is crucial to the differentiation of many cell types and participates in tumorigenesis and progression. This study investigated the role of Atoh1 in lung cancer development and its correlation with key members of the Wnt pathway. We used immunohistochemistry to examine the expressions of Atoh1, β-catenin, Axin, chibby, and Disabled-2 (Dab2) in 118 samples of lung cancer. We also detected the cytoplasmic and nuclear expression of Atoh1 in lung cancer tissues using western blot. Atoh1 nuclear expression was negatively correlated with differentiation level (p   =   0.004) and primary tumor stage (p   =   0.044) of lung cancer. Nuclear Atoh1 expression was positively correlated with nuclear expression of chibby (p   <   0.001) and Dab2 (p   <   0.001). Cytoplasmic Atoh1 expression was positively correlated with the cytoplasmic expression of Axin (p   =   0.028), chibby (p   <   0.001), and Dab2 (p   <   0.001). We conclude that the nuclear expression of Atoh1 was inversely correlated with the differentiation and primary tumor stage of lung cancers. The expression and localization of Atoh1 correlated with Axin, chibby, or Dab2. Atoh1 may be a potential therapeutic target for the inhibition of growth and progression of lung cancers.

Hepl, first described in 2008, is the fourth member of the Crk-associated substrate (CAS) family and is specifically expressed in the lung. Compared to other CAS proteins, Hepl has a varying effect on cell migration in different cell types. We speculated that Hepl may play a role in lung cancer invasion and metastasis. We quantified the expression and subcellular localization of Hepl in 143 non-small cell lung cancer (NSCLC) tissues, adjacent noncancerous tissues, and eight lung cancer cell lines using Western blotting, immunohistochemistry, and immunofluorescent staining. Expression of Hepl was correlated with the clinicopathological features of NSCLC. Hepl was overexpressed in 72.3 % (103/143) of the NSCLC tissues, compared to the adjacent noncancerous lung tissues (P = 0.022). Overexpression of Hepl was associated with lymph node metastasis and high TNM stage (P = 0.005 and P = 0.045, respectively). Kaplan–Meier survival curves and the log-rank test indicated that overexpression of Hepl correlated with poorer overall survival in NSCLC (P < 0.001), and Cox regression analysis demonstrated that overexpression of Hepl was an independent prognostic factor in NSCLC. Furthermore, cytoplasmic accumulation of Hepl was observed in a high metastatic potential lung cancer cell lines (H1299 and BE1), but not in low metastatic potential cell lines (LTE and A549). This study reveals that Hepl is overexpressed in the nucleus and aberrantly accumulates in the cytoplasm of NSCLC cells, and indicates that Hepl may play a role in the progression of lung cancer, including lymph node metastasis and TNM stage. Additionally, Hepl may be a useful prognostic factor in lung cancer.