Impact of the extent of negative lymph nodes in gastric adenocarcinoma undergoing primary surgical resection: An institutional report

Chen, Yen Jen; Yeh, Shin Ting; Ou, Liang; Lin, Ching-Heng; Chien, Chiang Ting

doi:10.1097/jcma.0000000000000500

Cited by 5 publications

(8 citation statements)

References 33 publications

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“…A total of 57 GAC patients who had received primary partial/subtotal/total gastrectomy with D2 lymph node dissection [1] and 17 overweight patients who had received a sleeve gastrectomy between January 2012 and December 2019 in Taipei Hospital, Ministry of Health and Welfare (MOHW), New Taipei City, Taiwan were retrospectively recruited. Their pathological T-/N-/M-status and cancer stages were designated according to the AJCC 8th edition [63].…”

Section: Study Participants Tissue Preparation and Dna Extractionmentioning

confidence: 99%

“…Gastric adenocarcinoma (GAC) is an aggressive malignancy that originates from the gastric mucosa (GM) and is one of the leading causes of cancer-related deaths in Taiwan [1]. Most oncologists have paid attention to the mutations or oncological effects of nuclear DNA (nDNA) [2], and a few have investigated the roles of mitochondrial DNA (mtDNA) and mitochondrial biogenesis and their roles in the carcinogenesis, progression, and prognosis of GAC [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

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Metabolic Reprogramming in Response to Alterations of Mitochondrial DNA and Mitochondrial Dysfunction in Gastric Adenocarcinoma

Chang

Lee

Pan

et al. 2022

IJMS

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We used gastric cancer cell line AGS and clinical samples to investigate the roles of mitochondrial DNA (mtDNA) alterations and mitochondrial respiratory dysfunction in gastric adenocarcinoma (GAC). A total of 131 clinical samples, including 17 normal gastric mucosa (N-GM) from overweight patients who had received sleeve gastrectomy and 57 paired non-cancerous gastric mucosae (NC-GM) and GAC from GAC patients who had undergone partial/subtotal/total gastrectomy, were recruited to examine the copy number and D310 sequences of mtDNA. The gastric cancer cell line AGS was used with knockdown (KD) mitochondrial transcription factor A (TFAM) to achieve mitochondrial dysfunction through a decrease of mtDNA copy number. Parental (PT), null-target (NT), and TFAM-KD-(A/B/C) represented the parental, control, and TFAM knocked-down AGS cells, respectively. These cells were used to compare the parameters reflecting mitochondrial biogenesis, glycolysis, and cell migration activity. The median mtDNA copy numbers of 17 N-GM, 57 NC-GM, and 57 GAC were 0.058, 0.055, and 0.045, respectively. The trend of decrease was significant (p = 0.030). In addition, GAC had a lower mean mtDNA copy number of 0.055 as compared with the paired NC-GM of 0.078 (p < 0.001). The mean mtDNA copy number ratio (mtDNA copy number of GAC/mtDNA copy number of paired NC-GM) was 0.891. A total of 35 (61.4%) GAC samples had an mtDNA copy number ratio ≤0.804 (p = 0.017) and 27 (47.4%) harbored a D310 mutation (p = 0.047), and these patients had shorter survival time and poorer prognosis. After effective knockdown of TFAM, TFAM-KD-B/C cells expressed higher levels of hexokinase II (HK-II) and v-akt murine thymoma viral oncogene homolog 1 gene (AKT)-encoded AKT, but lower levels of phosphorylated pyruvate dehydrogenase (p-PDH) than did the NT/PT AGS cells. Except for a higher level of p-PDH, the expression levels of these proteins remained unchanged in TFAM-KD-A, which had a mild knockdown of TFAM. Compared to those of NT, TFAM-KD-C had not only a lower mtDNA copy number (p = 0.050), but also lower oxygen consumption rates (OCR), including basal respiration (OCRBR), ATP-coupled respiration (OCRATP), reserve capacity (OCRRC), and proton leak (OCRPL)(all with p = 0.050). In contrast, TFAM-KD-C expressed a higher extracellular acidification rate (ECAR)/OCRBR ratio (p = 0.050) and a faster wound healing migration at 6, 12, and 18 h, respectively (all with p = 0.050). Beyond a threshold, the decrease in mtDNA copy number, the mtDNA D310 mutation, and mitochondrial dysfunction were involved in the carcinogenesis and progression of GACs. Activation of PDH might be considered as compensation for the mitochondrial dysfunction in response to glucose metabolic reprogramming or to adjust mitochondrial plasticity in GAC.

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Section: Study Participants Tissue Preparation and Dna Extractionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metabolic Reprogramming in Response to Alterations of Mitochondrial DNA and Mitochondrial Dysfunction in Gastric Adenocarcinoma

Chang

Lee

Pan

et al. 2022

IJMS

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“…7 However, which is the optimal system for LN staging and lymphadenectomy is still controversial. 8,9 LN metastasis plays a key role in the recurrence and longterm survival of patients with GC. 10 At present, D2 lymphadenectomy is the standard surgical procedure for treating patients with advanced GC undergoing radical gastrectomy.…”

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confidence: 99%

“…In patients with GC having total LNs of >15, a lower rate of negative LN is an independent predictor of poor prognosis (p = 0.026 and p = 0.015; HRs, 1.000, 0.272, and 0.180 for subgroups ≤37.5%, 37.5%-80.6%, and >80.6%, respectively). 9 At present, many prediction models for GC are available. Except for consideration of the early or advanced stage, the TNM system maintained by AJCC is still the principal standard.…”

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confidence: 99%