High expression of HSP60 and survivin predicts poor prognosis for oral squamous cell carcinoma patients.

BACKGROUND: HSP60 is a heat shock proteins (HSPs) family member and help mitochondrial protein to fold correctly. Survivin is one of the inhibitors of apoptosis protein family member, which plays a significant part in cancer progression. They were capable of forming HSP60-survivin complexes and involved in the development of various tumors. METHODS: The Cancer Genome Atlas (TCGA) database demonstrated that HSP60 and survivin and their correlation on mRNA expression level with OSCC patients. Besides, expression of HSP60 and survivin proteins was studied utilizing immunohistochemistry in tissue microarrays (TMA) in OSCC and in adjacent non-cancerous squamous epithelium (Non-CCSE) tissues. RESULTS: Significantly increased levels of HSP60 and survivin in most cancers compared to normal tissue by pan-cancer analysis. HSP60 and survivin proved a significantly increased expression in OSCC samples compared to Non-CCSE both on mRNA and protein (both P < 0.05). Additionally, elevated HSP60 displayed a positive correlation with survivin in terms of mRNA and protein expression levels (all P < 0.001). Patients with OSCC who had advanced clinical stage or lymph node metastasis (LNM) showed higher HSP60 expression (P = 0.004, P = 0.006, respectively). Higher levels of the proteins HSP60 and survivin were significantly inversely correlated relationship with OSCC patients' overall survival rates in multivariate survival analysis (P = 0.018, P = 0.040). From the above results, overexpression of HSP60 and survivin protein may serve as independent biomarkers predicting poor prognosis in OSCC. CONCLUSIONS: Elevated HSP60 and survivin might be served as novel poor prognosis biomarkers for surgically resected OSCC patients.

New insights into the important roles of phase seperation in the targeted therapy of lung cancer.

Lung cancer is a complex and heterogeneous disease characterized by abnormal growth and proliferation of lung cells. It is the leading cause of cancer-related deaths worldwide, accounting for approximately 18% of all cancer deaths. In recent years, targeted therapy has emerged as a promising approach to treat lung cancer, which involves the use of drugs that selectively target specific molecules or signaling pathways that are critical for the growth and survival of cancer cells. Liquid-liquid phase separation (LLPS) is a fundamental biological process that occurs when proteins and other biomolecules separate into distinct liquid phases in cells. LLPS is essential for various cellular functions, including the formation of membraneless organelles, the regulation of gene expression, and the response to stress and other stimuli. Recent studies have shown that LLPS plays a crucial role in targeted therapy of lung cancer, including the sequestration of oncogenic proteins and the development of LLPS-based drug delivery systems. Understanding the mechanisms of LLPS in these processes could provide insights into new therapeutic strategies to overcome drug resistance in lung cancer cells.

AXL in cancer: a modulator of drug resistance and therapeutic target.

AXL is a member of the TAM (TYRO3, AXL, and MERTK) receptor tyrosine kinases family (RTKs), and its abnormal expression has been linked to clinicopathological features and poor prognosis of cancer patients. There is mounting evidence supporting AXL's role in the occurrence and progression of cancer, as well as drug resistance and treatment tolerance. Recent studies revealed that reducing AXL expression can weaken cancer cells' drug resistance, indicating that AXL may be a promising target for anti-cancer drug treatment. This review aims to summarize the AXL's structure, the mechanisms regulating and activating it, and its expression pattern, especially in drug-resistant cancers. Additionally, we will discuss the diverse functions of AXL in mediating cancer drug resistance and the potential of AXL inhibitors in cancer treatment.

YAP1 synergize with YY1 transcriptional co-repress DUSP1 to induce osimertinib resistant by activating the EGFR/MAPK pathway and abrogating autophagy in non-small cell lung cancer.

YAP1 is a well-known core effector of the Hippo pathway in tumors, but its potential role in osimertinib resistance remained unexplored. Our study provides evidence that YAP1 acts as a potent promoter of osimertinib resistance. By inhibiting YAP1 with a novel inhibitor, CA3, and combining it with osimertinib, we observed a significant suppression of cell proliferation and metastasis, induction of apoptosis and autophagy, and a delay in the emergence of osimertinib resistance. Interestingly, CA3 combined with osimertinib executed its anti-metastasis and pro-tumor apoptosis in part through autophagy. Mechanistically, we found that YAP1, in collaboration with YY1, transcriptionally represses DUSP1, leading to the dephosphorylation of the EGFR/MEK/ERK pathway and YAP1 phosphorylation in osimertinib-resistant cells. Our results also validate that CA3, in combination with osimertinib, executes its anti-metastasis and pro-tumor apoptosis partly through autophagy and the YAP1/DUSP1/EGFR/MEK/ERK regulatory feedback loop in osimertinib-resistant cells. Remarkably, our findings illustrate that YAP1 protein is upregulated in patients after osimertinib treatment and osimertinib resistance. Overall, our study confirms that the YAP1 inhibitor CA3 increases DUSP1 with concomitant activation of the EGFR/MAPK pathway and induces autophagy to enhance the efficacy of third-generation EGFR-TKI treatments for NSCLC patients.

Increased expression of FAT4 suppress metastasis of lung adenocarcinoma through regulating MAPK pathway and associated with immune cells infiltration.

FAT4 is an extremely large atypical cadherin with crucial roles in the control of planar cell polarity (PCP) and regulation of the Hippo signaling pathway. Our study aims to clarify the FAT4 expression patterns, as well as the significance of FAT4 in predicting the prognosis and cancer immunity to non-small cell lung cancer (NSCLC). FAT4 mRNA and protein expressions were both underregulated in NSCLC and associated with poor prognosis in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). In addition, overexpress FAT4 with jujuboside A (JUA) or knockdown FAT4 with siRNA regulated the metastasis of LUAD through MAPK pathways. Moreover, the FAT4 expression included multiple immunological components to promote an immunosuppressive tumor microenvironment (TME). Furthermore, a study of the TCGA-LUAD cohort's DNA methylation results showed that most FAT4 DNA CpG sites were typically hypermethylated in NSCLC relative to the normal lung tissue. The DNA CpG sites cg25879360 and cg26389756 of FAT4 were found to be strongly associated with FAT4 expression in LUAD through the correlation study. In conclusion, this is the first to report the potential function of FAT4 in NSCLC. Hence, FAT4 could be used as a promising prognostic and immunological biomarker for NSCLC.

Overexpression of p-4EBP1 associates with p-eIF4E and predicts poor prognosis for non-small cell lung cancer patients with resection.

Eukaryotic initiation factor 4E (eIF4E) and its phosphorylated form (p-eIF4E) play a crucial role in the protein synthesis, both are under regulation of eIF4E-binding protein 1 (4EBP1) and mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs). This study aims to explore the potential prognostic significance of p-4EBP1 and p-eIF4E in NSCLC patients. The expression of p-4EBP1 and p-eIF4E in NSCLC patients was detected by immunohistochemistry (IHC) staining in tissue microarrays (TMAs) containing 354 NSCLC and 53 non-cancerous lung tissues (Non-CLT). The overexpression percentage of p-4EBP1 and p-eIF4E in lung squamous cell carcinoma (SCC) and adenocarcinoma (ADC) was significantly higher than that of Non-CLT. P-4EBP1 expression in patients with advanced clinical stage was higher than that in early stage. Expression of p-4EBP1 had a positive relationship with p-eIF4E expression both in lung SCC and ADC. NSCLC patients with high expression of p-4EBP1 and p-eIF4E alone or in combination had a lower survival rate than that of other phenotypes. For NSCLC patients, p-4EBP1 is an independent poor prognostic factor as well as clinical stage, LNM and pathological grade. Overexpression of p-4EBP1 and p-eIF4E might be novel prognostic marker for NSCLC, who possesses potential application value for NSCLC targeted therapy.

Overexpressed p-S6 associates with lymph node metastasis and predicts poor prognosis in non-small cell lung cancer.

BACKGROUND: Ribosomal protein S6 (S6), a downstream effect media of the AKT/mTOR pathway, not only is a part of 40S small subunit of eukaryotic ribosome, but also involves in protein synthesis and cell proliferation during cancer development. METHODS: In present study, we explore the association between phosphorylated S6 (p-S6) protein expression and clinicopathological features as well as prognostic implications in NSCLC. P-S6 was detected in tissue microarrays (TMAs) containing 350 NSCLC, 53 non-cancerous lung tissues (Non-CLT), and 88 cases of matched metastatic lymph node lesions via immunohistochemistry (IHC). Transwell assays and wound healing assay were used to assess the effects of p-S6 inhibition on NSCLC cell metastasis. RESULTS: The p-S6 expression in NSCLC was more evident than that in Non-CLT (p < 0.05). Compared to NSCLC patients who have no lymph node metastasis (LNM), those with LNM had higher p-S6 expression (p = 0.001). Regardless of lung squamous cell carcinoma (SCC) or adenocarcinoma (ADC), p-S6 was increased obviously in metastatic lymph nodes compared with matched primary cancers (p = 0.001, p = 0.022, respectively). Inhibition of p-S6 decreased the metastasis ability of NSCLC cells. In addition, p-S6 was an independent predicted marker for LNM in patients with NSCLC (p < 0.001). According to survival analysis, patients with highly expressed p-S6 had a lower survival rate compared with that with lower expression (p = 0.013). P-S6 is an unfavorable independent prognostic factor for NSCLC patients (p = 0.011). CONCLUSION: Increased expression of p-S6 is not only a novel predictive biomarker of LNM but also poor prognosis in NSCLC.

The multiple roles and therapeutic potential of HSP60 in cancer.

The molecular chaperone protein HSP60 is mainly distributed in mitochondria and assists protein folding under physiological and pathological conditions. Accumulating evidence suggests abnormally expressed HSP60 in cancer is associated with clinicopathological features and prognosis of cancer patients. HSP60 could be used as a new biomarker for both diagnostic and prognostic purpose and tumor therapy. In this review article, we briefly described the structure, functional cycle, and regulatory mechanism of HSP60, and summarized its functional diversity in cancer as well as recent progress related to the diagnostic application of HSP60 and inhibitors against HSP60, which could provide us a comprehensive understanding about the value of HSP60 in tumor management.

Exosome-mediated miR-7-5p delivery enhances the anticancer effect of Everolimus via blocking MNK/eIF4E axis in non-small cell lung cancer.

Everolimus is a kind of mammalian target of rapamycin (mTOR) inhibitors. Activated mitogen-activated protein kinase interacting kinases/eukaryotic translation initiation factor 4E (MNK/eIF4E) axis plays a crucial role in resistance to Everolimus in non-small cell lung cancer (NSCLC). The eIF4E phosphorylation increased by mTOR inhibitors is mainly mediated by MNKs. However, the mechanisms are poorly understood. Recently, extensive reprogramming of miRNA profiles has also been found after long-term mTOR inhibitor exposure. Our previous studies have confirmed that tumor suppressor miR-7-5p is decreased in A549 cells after treatment with Everolimus. Exactly, MNK1 is the target of miR-7-5p. In this study, we investigated the biological functions and potential molecular mechanisms of miR-7-5p in the NSCLC undergoing treatment with Everolimus. We confirmed that Everolimus targeted mTORC1 inducing NSCLC cells to secrete miR-7-5p-loaded exosomes in Rab27A and Rab27B-dependent manners. Loss of intracellular miR-7-5p induced phosphorylation of MNK/eIF4E axis, but a supplement of extra exosomal miR-7-5p could reverse it. Of note, both low expression of miR-7-5p and elevated MNK1 protein were associated with a poor prognosis of NSCLC. Both endogenous miR-7-5p and exo-miR-7-5p enhanced the therapeutic efficacy of Everolimus by inhibiting the proliferation, migration, and metastasis of NSCLC in vitro and in vivo. The combination of miR-7-5p with Everolimus induced apoptosis to exhibit a synergistic anticancer therapeutic efficacy through dual abrogation of MNK/eIF4E and mTOR in NSCLC. In conclusion, Everolimus decreases the intracellular miR-7-5p by releasing of miR-7-5p loaded exosomes from NSCLC cells in Rab27A and Rab27B dependent manners. Either endogenous miR-7-5p or exo-miR-7-5p combined with Everolimus can enhance the anticancer efficacy by targeting MNK/eIF4E axis and mTOR. Besides, both low levels of miR-7-5p and positive expression of MNK1 act as independent poor prognostic biomarkers for NSCLC. Therefore, restoring miR-7-5p carried by exosome may be a promising novel combined therapeutic strategy with Everolimus for NSCLC.

Aberrant Expression of ß-Catenin Correlates with Infiltrating Immune Cells and Prognosis in NSCLC.

Aims: ß-catenin is a critical regulating factor of the Wnt pathway, which is closely linked to tumorigenesis, tumor growth, metastasis, and tumor immunity. Our study focused on exploring the relationship between ß-catenin and clinicopathological features, prognosis, as well as infiltrating immune cells and immune scores, so as to illustrate its clinical significance in NSCLC. Materials and Methods: The ß-catenin mRNA (CTNNB1) and protein expression data were downloaded from the UALCAN and the UCSC Xena website, respectively. All tumor-immune infiltrating cells' data were downloaded from the TIMER platform and immune scores were downloaded from ESTIMATE website. The expression of ß-catenin protein in our cohort was measured by immunohistochemistry. Results: ß-catenin mRNA level was higher in lung adenocarcinoma (LUAD) compared to normal tissues (p < 0.001) and was related to overall survival (OS) (p < 0.001) and post-progression survival (PPS) (both p = 0.049) in LUAD. Aberrant ß-catenin protein expression was higher in male and lung squamous cell carcinoma (LUSC) patients (both p = 0.001). Also, it was considered to be a prognosis factor independently (p = 0.034). In addition, ß-catenin protein was negatively correlated with CD8+T cells (r = -0.128, p = 0.008), neutrophils (r = -0.198, p < 0.001), immune score (r = -0.109, p = 0.024), stromal score (r = -0.097, p = 0.045), and ESTIMATE score (r = -0.113, p = 0.020). Conclusions: Aberrant ß-catenin protein expression was evidently higher in NSCLC and might serve as a biomarker for poor prognosis. Most importantly, ß-catenin protein might play an important part in tumor immunity and the tumor microenvironment by inhibiting the infiltration of CD8+ T cells and neutrophils.

Overexpression of P4HA1 associates with poor prognosis and promotes cell proliferation and metastasis of lung adenocarcinoma.

Prolyl 4-hydroxylase subunit alpha 1 (P4HA1) is the core active catalytic portion of prolyl 4-hydroxylase, and has contributed to tumorigenesis in several cancers. In this study, we identified that P4HA1 mRNA and protein are both up-regulated in non-small cell lung cancer (NSCLC). Besides, overexpressed P4HA1 is correlated with poor clinical outcomes and serve as an independent prognosis biomarker in lung adenocarcinoma (LUAD), but not lung squamous cell carcinoma (LUSC). In vitro studies, decreased P4HA1 significantly inhibits proliferation and cell cycle, by regulating cyclin-dependent kinases (CDKs), cyclins and CDK inhibitor (CKI). Moreover, via inhibiting epithelial-mesenchymal transition (EMT) and matrix metalloprotease (MMPs), dysregulation of P4HA1 could restrain the tumor cell invasion and metastasis of lung adenocarcinoma. In addition, we found that P4HA1 could enhance cell stemness and cisplatin-resistance in lung adenocarcinoma. In summary, P4HA1 plays a crucial role in the development of NSCLC and may provide a brand-new target for lung cancer treatment.

New insights into the important roles of tumor cell-intrinsic PD-1.

PD-1 (Programmed cell death protein-1) is mainly expressed in various immune cells, while its ligands PD-L1/PD-L2 (Programmed death ligand-1/Programmed death ligand-2) are mostly expressed in tumor cells. Generally, the binding of PD-L1/PD-L2 and PD-1 could lead to the tumor immune evasion. However, some recent studies showed that PD-1 could also be expressed in tumor cells and could activate mTOR (Mammalian Target of Rapamycin) or Hippo signaling pathway, therefore facilitating tumor proliferation independent of the immune system. While there was evidence that tumor cell-intrinsic PD-1 inhibited the activation of AKT and ERK1/2 pathways, thereby inhibiting tumor cell growth. Based on TCGA and CCLE database, we found that PD-1 was expressed in a variety of tumors and was associated with patient's prognosis. Besides, we found that PD-1 may be involved in many carcinogenic signaling pathway on the basis of PD-1 gene enrichment analysis of cancer tissues and cancer cells. Our understanding of the tumor cell-intrinsic PD-1 function is still limited. This review is aimed at elaborating the potential effects of tumor cell-intrinsic PD-1 on carcinogenesis, providing a novel insight into the effects of anti-PD-1/PD-L1 immunotherapy, and helping to open a major epoch of combination therapy.

Co-expression of PD-L1 and HIF-1α predicts poor prognosis in Patients with Non-small Cell Lung Cancer after surgery.

Purpose: PD-L1 is highly expressed in multiple cancers and suppresses anticancer immunity. HIF-1α, as a vital transcription factor, could regulate the proliferation, metastasis, and apoptosis of cancer cells. The aim of this study was to explore the correlation between PD-L1 and HIF-1α protein and further estimate its clinicopathological/prognostic impact on NSCLC patients. Methods: In this study, expression of PD-L1 and HIF-1α protein was detected by immunohistochemistry in tissue microarrays of NSCLC and non-cancerous tissues. Results: Expression of PD-L1 and HIF-1α protein was evidently elevated in NSCLC tissues compared with non-cancerous control lung tissues (both P<0.05). Also, PD-L1 was higher in male, lung SCC patients with lymph node metastasis (all P<0.05). There was a positive link between PD-L1 and HIF-1α in NSCLC (r=0.177, P=0.005). What's more, overall survival of lung ADC patients had to do with PD-L1 and clinical stage, while that of SCC patients was related to HIF-1α, pathological grade and LNM status (all P<0.05). Furthermore, multivariate analysis confirmed that PD-L1 and HIF-1α were considered to be independent prognostic factors for NSCLC patients (both P<0.05). Conclusion: PD-L1 and HIF-1α may serve as attractive independent worse prognostic biomarkers for NSCLC patients and the combined evaluation of PD-L1 and HIF-1α may also be valuable for prognosis judgment. Additionally, expression of PD-L1 was positively correlated with HIF-1α, which may provide evidences for a novel combinational therapy targeting PD-L1 and HIF-1α in NSCLC patients.

Overexpression of HSP10 correlates with HSP60 and Mcl-1 levels and predicts poor prognosis in non-small cell lung cancer patients.

BACKGROUND: HSP60 and its partner HSP10 are members of heat shock proteins (HSPs) family, which help mitochondrial protein to fold correctly. Mcl-1, a member of the Bcl-2 family, plays a crucial role in regulation of cell apoptosis. Aberrant expression of HSP10, HSP60 and Mcl-1 is involved in the development of many tumors. OBJECTIVE: To examine the association between expression of HSP10, HSP60 and Mcl-1 and clinicopathological features of non-small cell lung cancer (NSCLC). METHODS: Tissue microarrays including 53 non-cancerous lung tissues (Non-CLT) and 354 surgically resected NSCLC were stained with anti-HSP10, anti-HSP60 and anti-Mcl-1 antibodies respectively by immunohistochemistry. RESULTS: Higher expression of HSP10, HSP60 and Mcl-1 was found in NSCLC compared with Non-CLT. Both individual and combined HSP10 and HSP60 expression in patients with clinical stage III was higher than that in stage I ∼ II. Expression of HSP10 showed a positive correlation with HSP60 and Mcl-1. Overall survival time of NSCLC patients was remarkably shorter with elevated expression of HSP10, HSP60 and Mcl-1 alone and in combination. Moreover overexpression of HSP10 and Mcl-1 was poor independent prognostic factor for lung adenocarcinoma patients. CONCLUSIONS: High expression of HSP10, HSP60 and Mcl-1 might act as novel biomarker of poor prognosis for NSCLC patients.

Overexpression of FADD and Bcl-XS proteins as novel prognostic biomarkers for surgically resected non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the most widespread cancer with increasing morbidity and mortality. FAS-associated protein with death domain (FADD) is considered as an essential instrument in cell death, whereas Bcl-XS promotes apoptosis through inhibiting the activity of Bcl-2 and Bcl-XL. OBJECTIVE AND METHODS: We detected the expression of FADD and Bcl-XS in resected NSCLC tissues by immunohistochemistry, and investigated their association with clinicopathological characteristics and prognostic significance of NSCLC patients. RESULTS: Bcl-XS expression was significantly increased in well and moderate differentiated lung SCC (P= 0.004). Lung ADC patients with overexpression of FADD and lung SCC patients with low expression of Bcl-XS had importantly lower overall survival rates by Kaplan-Meier analysis (P= 0.033, P= 0.02, respectively). Multivariate analysis confirmed that elevated expression of FADD was an independent poor prognostic factor for patients with surgically resected lung ADC (P= 0.027) and increased expression of Bcl-XS was an independent good prognostic factor for patients with surgically resected lung SCC (P= 0.016)CONCLUSION: Elevated expression of FADD was identified as independent poor prognostic factor for patients with surgically resected lung ADC, however, increased expression of Bcl-XS was an independent good prognostic biomarker for patients with surgically resected lung SCC.

Clinical significance of PD-L1 expression in patients with surgically resected non-small cell lung cancer. / PD-L1在非小细胞肺癌中表达的临床意义.

OBJECTIVES: To explore the expression of programmed death ligand-1 (PD-L1) as well as the correlation between the expression and the clinicopathological features or prognosis in non-small cell lung cancer (NSCLC). METHODS: The expression of PD-L1 protein in 254 cases of surgically resected lung adenocarcinoma (L-ADC), 228 cases of surgically resected lung squamous cell cancer (L-SCC), and 99 cases of non-cancerous control lung tissues was detected with immunohistochemical SP method. The correlation between the PD-L1 expression and clinicopathological features was analyzed. Kaplan-Meier univariate and Cox multivariate regression analyses were performed to assess the prognosis of patients with L-ADC and L-SCC, respectively. RESULTS: Positive percentage of PD-L1 protein expression was higher in the tissues of L-ADC and L-SCC than that in the non-cancerous control lung tissues respectively (both P<0.05). Positive percentage of PD-L1 protein expression was higher in the tissues of L-SCC than that in the tissues of L-ADC (P<0.05). However, there were no correlation between the expression of PD-L1 and age, gender, pathological grades, clinical stages, and lymph node metastasis in L-ADC and L-SCC respectively (all P>0.05). Overall survival rate was evidently lower in the L-ADC patients with positive expression of PD-L1 protein compared to the patients with negative staining of PD-L1 (P<0.01). Multivariate Cox regression analysis further identified that the L-ADC patients of positive expression of PD-L1 protein had a poor prognosis (P<0.01). CONCLUSIONS: The positive percentage of PD-L1 protein expression is higher in the L-SCC patients than that in the L-ADC patients. Positive expression of PD-L1 protein can be served as an independent prognostic factor of poor prognosis in the patients with L-ADC.

Comprehensive analysis of the mechanism and treatment significance of Mucins in lung cancer.

Aberrant expression of mucin proteins has played a complex and essential role in cancer development and metastasis. Members of the mucin family have been intimately implicated in lung cancer progression, metastasis, survival and chemo-resistance. During the progression of lung cancer, mucin proteins have involved all of the procession of lung cancer, which is interacted with many receptor tyrosine kinases signal pathways and mediated cell signals for tumor cell growth and survival. Mucins thus have been considerable as the indicator of negative prognosis and desirable therapeutic targets of lung cancers. In this review, we comprehensively analyzed the role of each member of the mucin family in lung cancer by combining open-accessed database analysis and assembling cutting-edge information about these molecules.

miR-4634 augments the anti-tumor effects of RAD001 and associates well with clinical prognosis of non-small cell lung cancer.

MicroRNA (miRNA) is involved in the physiological and pathological processes of various malignancies. In this study, miRNA microarray analysis showed that miR-4634 levels in A549 cells increased significantly after everolimus (RAD001) treatment. Decreased expression of miR-4634 was also found in non-small-cell lung carcinoma (NSCLC) cell lines and patients' tumors by qPCR. Additionally, a combination of miR-4634 and RAD001 exerted synergistic antitumor efficacy by inhibiting cell proliferation, migration, and colony formation. High expression of miR-4634 was significantly more common in non-cancerous lung tissue than adenocarcinoma or squamous cell carcinoma tissue (72.8%, 45.7%, and 50.9%, respectively; P < 0.001). Furthermore, high expression of miR-4634 was found to be more frequent in patients without lymph node metastasis (P = 0.037) by in-situ hybridization. Importantly, through univariate and multivariate analysis, high miR-4634 expression was associated with better prognosis of NSCLC patients. In conclusion, miR-4634 may act as a tumor suppressor in NSCLC, and to augment the efficacy of RAD001, co-treatment of miR-4634 and RAD001 might be a potential mTOR-targeted cancer therapy strategy for NSCLC patients. High expression of miR-4634 could be an independent good prognostic biomarker for NSCLC.

Osimertinib for compound EGFR exon 19 deletion/T790M mutated lung squamous cell carcinoma.

The role of the epidermal growth factor receptor (EGFR) mutation status testing in lung squamous cell carcinoma (SqCC) remains controversial. Evidence of the effectiveness of osimertinib in SqCC with EGFR T790M mutation is limited. Here, we describe a hitherto unreported case of a stage III SqCC patient with compound mutation of EGFR exon 19 deletion (19Del) and T790M mutation. Pathological complete tumor response was achieved after treatment with osimertinib. We suggest that EGFR mutation testing should be performed in Asian patients who have not been definitively diagnosed with SqCC due to small lung biopsy samples. Osimertinib has shown good efficacy in SqCC harboring a "primary" resistance mechanism (EGFR T790M). KEY POINTS: An unreported case of stage III squamous cell carcinoma with synchronous occurrence of EGFR exon 19 deletion (19Del) and T790M mutation. Complete tumor response was achieved after treatment with osimertinib. EGFR mutation testing should be performed in Asian patients who are not definitively diagnosed with SqCC due to small lung biopsy samples. Osimertinib has shown good efficacy in SqCC harboring a "primary" resistance mechanism (EGFR T790M).