Background
An association between a nonmedicinal herbal diet and nasopharyngeal carcinoma (NPC) has often been hypothesized but never thoroughly investigated.
Methods
This study enrolled a total of ...2469 patients with incident NPC and 2559 population controls from parts of Guangdong and Guangxi Provinces in southern China between 2010 and 2014. Questionnaire information was collected on the intake of traditional herbal tea and herbal soup as well as the specific herbal plants used in soups and other potentially confounding lifestyle factors. Multivariate logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the NPC risk in association with herbal tea and soup intake.
Results
Ever consumption of herbal tea was not associated with NPC risk (OR, 1.03; 95% CI, 0.91‐1.17). An inverse association was observed for NPC among ever drinkers of herbal soup (OR, 0.78; 95% CI, 0.67‐0.90) but without any monotonic trend with an increasing frequency or duration of herbal soup consumption. Inverse associations with NPC risk were detected with 9 herbal plants used in herbal soup, including Ziziphus jujuba, Fructus lycii, Codonopsis pilosula, Astragalus membranaceus, Semen coicis, Smilax glabra, Phaseolus calcaratus, Morinda officinalis, and Atractylodes macrocephala (OR range, 0.31‐0.79).
Conclusions
Consuming herbal soups including specific plants, but not herbal tea, was inversely associated with NPC. If replicated, these results might provide potential for NPC prevention in endemic areas.
Consuming herbal soups is inversely associated with nasopharyngeal carcinoma in the endemic region of southern China. Nine herbal types are identified as responsible for this inverse association.
Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies of the digestive tract in East Asian countries. Multimodal therapies, including adjuvant chemotherapy and neo-adjuvant ...chemotherapy, have become more often used for patients with advanced ESCC. However, the chemotherapy effect is often limited by patients' drug resistance. This study demonstrated that EIF5A2 (eukaryotic translation initiation factor 5A2) overexpression induced stemness and chemoresistance in ESCC cells. We showed that EIF5A2 overexpression in ESCC cells resulted in increased chemoresistance to 5-fluorouracil (5-FU), docetaxel and taxol. In contrast, shRNAs suppressing eIF5A2 increased tumor sensitivity to these chemotherapeutic drugs. In addition, EIF5A2 overexpression was correlated with a poorer overall survival in patients with ESCC who underwent taxane-based chemotherapy after esophagectomy (P < 0.05). Based on these results, we suggest that EIF5A2 could be a predictive biomarker for selecting appropriate chemo-treatment for ESCC patients and EIF5A2 inhibitors might be considered as combination therapy to enhance chemosensitivity in patients with ESCC.
This study aimed to investigate the prevalence of tumor programmed death-ligand 1 (PD-L1) expression in Chinese patients with advanced Non-Small Cell Lung Cancer (NSCLC).
Tumor tissues with ...histologically confirmed stage IIIB/IV NSCLC were retrospectively obtained from 10 centers in China. PD-L1 expression was determined using the PD-L1 IHC 22C3 pharmDx kit (Agilent, Santa Clara, CA, USA) and the samples were repetitively assayed with the PD-L1 IHC 22C3 Ab concentrate (Agilent, Santa Clara, CA, USA).
Out of 901 patients who met the inclusion criteria, 879 (97.6%) had evaluable PD-L1 data. The number of patients with a PD-L1 tumor proportion score (TPS) < 1%, 1-49%, and ≥ 50% (corresponding to PD-L1 non-expression, low expression, and high expression) was 424 (48.2%), 266 (30.3%), and 189 (21.5%), respectively. PD-L1 expression was more likely to be found in patients younger than 75 years, men, current or former smokers, those with good performance status (PS) scores, and those with a wild-type epidermal growth factor receptor (EGFR). PD-L1 TPS ≥ 50% and ≥ 1% were respectively 28.0% and 50.2% among patients negative for both EGFR mutation and anaplastic lymphoma kinase (ALK) rearrangement. PD-L1 expression determined using the 22C3 antibody concentrate and pharmDx kit had comparable results.
The prevalence of PD‑L1 expression in advanced NSCLC was consistent with that reported in the global EXPRESS study. Age, gender, smoking history, PS scores, and EGFR/ALK mutation status affected PD-L1 expression. The 22C3 antibody concentrate appears to be an alternative reagent for the PD-L1 assay.
POTE ankyrin domain family, member G (poteg) belongs to POTE family. The POTE family is composed of many proteins which are very closely related and expressed in prostate, ovary, testis, and ...placenta. Some POTE paralogs are related with some cancers. Here we showed that down‐regulation of POTEG was detected in about 60% primary esophageal squamous cell carcinoma (ESCC) tumor tissues. Clinical association studies determined that POTEG down‐regulation was significantly correlated with tumor differentiation, lymph nodes metastasis and TNM staging. Kaplan‐Meier analysis determined that POTEG down‐regulation was associated with poorer clinical outcomes of ESCC patients (P = 0.026). Functional studies showed that POTEG overexpression could suppress tumor cell growth and metastasis capacity in vitro and in vivo. Molecular analyses revealed that POTEG downregulated CDKs, leading to subsequent inhibition of Rb phosphorylation, and consequently arrested Cell Cycle at G1/S Checkpoint. POTEG overexpression induced apoptosis by activating caspases and PARP, and regulating canonical mitochondrial apoptotic pathways. On the other side, POTEG inhibited epithelial‐mesenchymal transition and suppressed tumor cell metastasis. In conclusion, our study reveals a functionally important control mechanism of POTEG in esophageal cancer pathogenesis, suggesting potential use in the ESCC intervention and therapeutic strategies.
Background: Primary liver cancer, of which around 75–85% is hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing ...a significant threat to the life and health of the Chinese people. Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China in June 2017, which were updated by the National Health Commission in December 2019, additional high-quality evidence has emerged from researchers worldwide regarding the diagnosis, staging, and treatment of liver cancer, that requires the guidelines to be updated again. The new edition (2022 Edition) was written by more than 100 experts in the field of liver cancer in China, which not only reflects the real-world situation in China but also may reshape the nationwide diagnosis and treatment of liver cancer. Key Messages: The new guideline aims to encourage the implementation of evidence-based practice and improve the national average 5-year survival rate for patients with liver cancer, as proposed in the “Health China 2030 Blueprint.”
Consuming herbal soups was inversely associated with NPC in the endemic region of southern China. Nine herbal types were identified to be responsible for this inverse association.
Abstract Background Anaplastic lymphoma kinase ( ALK ) test in advanced non‐small cell lung cancer (NSCLC) can help physicians provide target therapies for patients harboring ALK gene rearrangement. ...This study aimed to investigate the real‐world test patterns and positive rates of ALK gene rearrangements in advanced NSCLC. Methods In this real‐world study (ChiCTR2000030266), patients with advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1, 2018 and December 31, 2019 were retrospectively analyzed. Interpretation training was conducted before the study was initiated. Quality controls were performed at participating centers using immunohistochemistry (IHC)‐VENTANA‐D5F3. The positive ALK gene rearrangement rate and consistency rate were calculated. The associated clinicopathological characteristics of ALK gene rearrangement were investigated as well. Results The overall ALK gene rearrangement rate was 6.7% in 23,689 patients with advanced NSCLC and 8.2% in 17,436 patients with advanced lung adenocarcinoma. The quality control analysis of IHC‐VENTANA‐D5F3 revealed an intra‐hospital consistency rate of 98.2% (879/895) and an inter‐hospital consistency rate of 99.2% (646/651). IHC‐VENTANA‐D5F3 was used in 53.6%, real‐time polymerase chain reaction (RT‐PCR) in 25.4%, next‐generation sequencing (NGS) in 18.3%, and fluorescence in‐situ hybridization (FISH) in 15.9% in the adenocarcinoma subgroup. For specimens tested with multiple methods, the consistency rates confirmed by IHC‐VENTANA‐D5F3 were 98.0% (822/839) for FISH, 98.7% (1,222/1,238) for NGS, and 91.3% (146/160) for RT‐PCR. The overall ALK gene rearrangement rates were higher in females, patients of ≤ 35 years old, never smokers, tumor cellularity of > 50, and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup (all P < 0.05). Conclusions This study highlights the real‐world variability and challenges of ALK test in advanced NSCLC, demonstrating a predominant use of IHC‐VENTANA‐D5F3 with high consistency and distinct clinicopathological features in ALK ‐positive patients. These findings underscore the need for a consensus on optimal test practices and support the development of refined ALK test strategies to enhance diagnostic accuracy and therapeutic decision‐making in NSCLC.
Abstract
Programmed death-ligand 1 (PD-L1) is a trans-membrane protein and co-inhibitory factor of the immune response. PD-L1 can combine with its receptor (PD-1) to reduce the proliferation of ...PD-1-positive cells and induce apoptosis. Therefore, PD-L1 was employed as a prognostic marker and a target for anti-cancer immunotherapy in blocking the PD-1 and PD-L1 checkpoints. PD-L1 is highly expressed in various malignancies, including head and neck squamous cell carcinoma (HNSCC). HNSCC is the sixth most common cancer worldwide, with high incidence and mortality rates in China. Although PD-L1 expression has been widely investigated, the PD-L1 expression status in Chinese HNSCC patients (pts) is largely unrevealed. The primary objective of this study was to determine the prevalence of PD-L1 expression with the Combined Positive Score (CPS) ≥20 in Chinese pts with recurrent or metastatic (R/M) HNSCC. The secondary objectives were to determine the prevalence of CPS≥1 in pts with R/M HNSCC and to study the difference in the demographic characteristics, clinicopathological parameters, treatment status, and other available biomarkers between the PD-L1 CPS≥20 group and the PD-L1 CPS<20 group. This study was a multi-center retrospective analysis of data from six centers in China from August 9, 2021, to February 28, 2022. Pts with histologically/cytologically confirmed diagnoses of R/M HNSCC were included. PD-L1 expression was assessed by IHC using the 22C3 PharmDx assay (Agilent, Santa Clara, CA, USA) and was determined using a CPS. The Chi-square test, Fisher’s exact test, or Wilcoxon rank sum test would be used to compare the prevalence of these variables among pts between the PD-L1 CPS≥20 group and the PD-L1 CPS<20 group. Out of 406 enrolled pts with R/M HNSCC, 402 testing pts were included in the final analysis. For all testing R/M HNSCC pts, 168 pts (41.8% 95% CI 36.92-46.78) had PD-L1 expression with CPS ≥20. In addition, 337 pts (83.8% 95% CI 79.86-87.29) had PD-L1 expression (CPS≥1). For the testing pts, there were statistically significant differences in variables of gender (P < 0.001), smoking habit (P = 0.0138 for non-smokers versus current smokers), and primary tumor site (P < 0.001 for hypopharynx versus oral cavity and P = 0.0304 for larynx versus oral cavity) between the PD-L1 CPS≥20 group and the PD-L1 CPS<20 group. In summary, in Chinese R/M HNSCC pts, most pts (83.8%) had PD-L1 expression, and two-fifths (41.8%) had PD-L1 expression with CPS ≥20. Prevalence of PD-L1 among Chinese pts with R/M HNSCC was consistent with that reported in the global KEYNOTE-048 study. PD-L1 expression was significantly associated with gender, smoking history and primary tumor site. Our findings of the variables related to the PD-L1 expression levels can supply adjuvant evidence for clinical practice and are a solid basis for future research on immunotherapy.
Citation Format: Haizhen Lu, Dong Kuang, Lili Jiang, Jingping Yun, Qingxin Xia, Jian Wang, Pei Duan, Ping Zhou, Shengbing Zang, Yiping Jin, Xiangnan Jiang, Jielin Li, Wenmin Tang, Jiansong Zhou, Jihua Chen, Jianming Ying. The PD-L1 protein expression in Chinese patients with recurrent or metastatic head and neck squamous cell carcinoma: A multi-center retrospective study. abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5463.
Abstract
Introduction: Programmed cell death ligand-1 (PD-L1) is the ligand of programmed cell death-1 (PD-1), a member of the immunoglobulin gene superfamily that plays a role in programmed cell ...death. Accumulating evidence of anti-PD-1 therapy has showed improved survival benefit for esophageal cancer (EC) patients. PD-L1 has emerged as a crucial predictor for efficacy of immunotherapy. However, the understanding of PD-L1 as a biomarker is complicated by various immunohistochemistry platforms, PD-L1 antibodies, scoring systems, and cut-offs for immunotherapy. Although PD-L1 expression has been widely investigated, the real-world PD-L1 expression status in Chinese patients with advanced EC nationwide with unified testing platform, antibody, scoring system and cut-off is largely unrevealed.
Methods: The present study was a nationwide multi-center retrospective analysis of data from six centers in China from August 9, 2021, to February 28, 2022. Patients with histologically or cytologically confirmed diagnoses of advanced EC were included. The primary outcome was the prevalence of high PD-L1 expression in patients with advanced EC. Immunohistochemical analysis of PD-L1 expression was performed by using the PD-L1 IHC 22C3 pharmDx assay in EC specimens. PD-L1 protein expression was assessed by using a combined positive score (CPS). The CPS≥ 10 was defined as a high PD-L1 high expression. The Chi-square test, Fisher’s exact test, or Wilcoxon rank sum test was used to compare the PD-L1 prevalence across demographic, clinicopathologic parameters, treatment status and other biomarkers.
Results: Out of 488 enrolled patients with advanced EC, 482 patients were included in the final analysis. For all testing EC patients, 207 patients (42.9% 95% CI 38.48-47.50) were PD-L1 high expression (CPS≥10). Between the PD-L1 high (CPS≥10) group and PD-L1 low (CPS<10) group, there were statistically significant differences in gender (P=0.046), alcohol consumption (P = 0.011), distant metastatic lesion number of patients with stage IV (P = 0.032), surgery (P = 0.012), systemic therapy (P = 0.004), and chemotherapy (P=0.004).
Conclusion: In summary, the prevalence of high PD-L1 expression (CPS≥10) in Chinese patients with advanced EC in real-world setting using 22C3 assay is consistent with previous data in global clinical trials. Our findings of the related clinicopathological and treatment features to the PD-L1 expression can provide supplementary information for decision-making of immunotherapy and facilitate the better understanding of mechanism underlying PD-L1 and anti-tumor immunity.
Citation Format: Liyan Xue, Jiaqi Wang, Dong Kuang, Jingping Yun, Yuan Li, Lili Jiang, Daoyuan Wu, Pei Duan, Shixun Lu, Yan Jin, Du He, Jing Qian, Wenmin Tang, Yan Wang, Jielin Li, Jianming Ying. The PD-L1 protein expression in Chinese patients with advanced esophageal cancers: a multi-center retrospective study abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2180.
Abstract
Targetable drivers governing to 5-fluorouracil and cisplatin (5FU+CDDP) resistance remain elusive due to the paucity of physiologically and therapeutically relevant models. Accordingly, we ...established 5FU+CDDP resistant intestinal subtype GC patient-derived organoid lines. JAK/STAT signaling and its downstream, adenosine deaminases acting on RNA 1 (ADAR1), are shown to be concomitantly upregulated in the resistant lines. ADAR1 was demonstrated to confer chemoresistance and self-renewal in an RNA editing-dependent manner. WES-seq coupled with RNA-seq identified enrichment of hyperedited lipid metabolism genes in the resistant lines. Mechanistically, ADAR1-mediated A-to-I editing on 3’UTR of stearoyl-CoA desaturase (SCD1) increased binding of KH domain-containing, RNA-binding, signal transduction-associated 1 (KHDRBS1), thereby augmenting SCD1 mRNA stability. Consequently, SCD1 facilitates lipid droplet formation to alleviate chemotherapy-induced ER stress and enhances self-renewal through increasing β-catenin expression. Pharmacological inhibition of SCD1 abrogated chemoresistance and tumor-initiating cell frequency. Clinically, high proteomic level of ADAR1 and SCD1, or high SCD1 editing/ADAR1 mRNA signature score predicts a worse prognosis. Together, we unveiled a novel actionable target to circumvent chemoresistance.
Citation Format: Jia Jian Loh, Tin Lok Wong, Shixun Lu, Helen HN Yan, Hoi Cheong Siu, Ren Xi, Dessy Chan, Max JF Kam, Lei Zhou, Man Tong, John A. Copland, Leilei Chen, Jingping Yun, Suet Yi Leung, Stephanie Ma. ADAR1-mediated RNA editing of SCD1 links lipid metabolism to gastric cancer drug resistance and self-renewal abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1755.
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