Long non-coding RNAs (lncRNAs) are frequently dysregulated in multiple malignancies, demonstrating their potential oncogenic or tumor-suppressive roles in tumorigenesis. Herein, we reported the identification of a novel lncRNA, linc00665 (ENST00000590622), which was markedly upregulated in lung adenocarcinoma (LUAD) tissues and might serve as an independent predictor for poor prognosis. Functional assays indicated that linc00665 reinforced LUAD cell proliferation and metastasis in vitro and in vivo. Mechanistically, transcription factor SP1 induced the transcription of linc00665 in LUAD cells, which exerted its oncogenic role by functioning as competing endogenous RNA (ceRNA) for miR-98 and subsequently activating downstream AKR1B10-ERK signaling pathway. Together, our study elucidates oncogenic roles of linc00665–miR98–AKR1B10 axis in LUAD tumorigenesis, which may serve as potential diagnostic biomarkers and therapeutic targets.

SUMMARY The aims of this pilot study are to evaluate the feasibility, safety, and effectiveness of conducting an enhanced nutritional support pathway including extended preoperative nutritional support and one month home enteral nutrition (HEN) for patients who underwent enhanced recovery after esophagectomy. We implemented extended preoperative nutritional support and one month HEN after discharge for patients randomized into an enhanced nutrition group and implemented standard nutritional support for patients randomized into a conventional nutrition group. Except the nutritional support program, both group patients underwent the same standardized enhanced recovery after surgery programs of esophagectomy based on published guidelines. Patients were assessed at preoperative day, postoperative day 7 (POD7), and POD30 for perioperative outcomes and nutritional status. To facilitate the determination of an effect size for subsequent appropriately powered randomized clinical trials and assess the effectiveness, the primary outcome we chose was the weight change before and after esophagectomy. Other outcomes including body mass index (BMI), lean body mass (LBM), appendicular skeletal muscle mass index (ASMI), nutrition-related complications, and quality of life (QoL) were also analyzed. The intention-to-treat analysis of the 50 randomized patients showed that there was no significant difference in baseline characteristics. The weight (−2.03 ± 2.28 kg vs. −4.05 ± 3.13 kg, P = 0.012), BMI (−0.73 ± 0.79 kg/m2 vs. −1.48 ± 1.11 kg/m2, P = 0.008), and ASMI (−1.10 ± 0.37 kg/m2 vs. −1.60 ± 0.66 kg/m2, P = 0.010) loss of patients in the enhanced nutrition group were obviously decreased compared to the conventional nutrition group at POD30. In particular, LBM (48.90 ± 9.69 kg vs. 41.96 ± 9.37 kg, p = 0.031) and ASMI (7.56 ± 1.07 kg/m2 vs. 6.50 ± 0.97 kg/m2, P = 0.003) in the enhanced nutrition group were significantly higher compared to the conventional nutrition group at POD30, despite no significant change between pre- and postoperation. In addition, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 scores revealed that enhanced nutritional support improved the QoL of patients in physical function (75.13 ± 9.72 vs. 68.33 ± 7.68, P = 0.009) and fatigue symptom (42.27 ± 9.93 vs. 49.07 ± 11.33, P = 0.028) compared to conventional nutritional support. This pilot study demonstrated that an enhanced nutritional support pathway including extended preoperative nutritional support and HEN was feasible, safe, and might be beneficial to patients who underwent enhanced recovery after esophagectomy. An appropriately powered trial is warranted to confirm the efficacy of this approach.

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